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1
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Verbeek R, Vandekerckhove L, Van Cleemput J. Update on human herpesvirus 7 pathogenesis and clinical aspects as a roadmap for future research. J Virol 2024; 98:e0043724. [PMID: 38717112 PMCID: PMC11237674 DOI: 10.1128/jvi.00437-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2024] Open
Abstract
Human herpesvirus 7 (HHV-7) is a common virus that is associated with various human diseases including febrile syndromes, dermatological lesions, neurological defects, and transplant complications. Still, HHV-7 remains one of the least studied members of all human betaherpesviruses. In addition, HHV-7-related research is mostly confined to case reports, while in vitro or in vivo studies unraveling basic virology, transmission mechanisms, and viral pathogenesis are sparse. Here, we discuss HHV-7-related literature linking clinical syndromes to the viral life cycle, epidemiology, and viral immunopathogenesis. Based on our review, we propose a hypothetical model of HHV-7 pathogenesis inside its host. Furthermore, we identify important knowledge gaps and recommendations for future research to better understand HHV-7 diseases and improve therapeutic interventions.
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Affiliation(s)
- Rianne Verbeek
- HIV Cure Research Center, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Linos Vandekerckhove
- HIV Cure Research Center, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Jolien Van Cleemput
- HIV Cure Research Center, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
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Zheng Y, Feng J, Ling M, Yu Y, Tao Y, Wang X. A comprehensive review on targeting cluster of differentiation: An attractive strategy for inhibiting viruses through host proteins. Int J Biol Macromol 2024; 269:132200. [PMID: 38723834 DOI: 10.1016/j.ijbiomac.2024.132200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 04/20/2024] [Accepted: 05/06/2024] [Indexed: 05/13/2024]
Abstract
Viral infections continue to pose a significant global public health threat. Targeting host proteins, such as cluster of differentiation (CD) macromolecules, may offer a promising alternative approach to developing antiviral treatments. CDs are cell-surface biological macromolecules mainly expressed on leukocytes that viruses can use to enter cells, thereby evading immune detection and promoting their replication. The manipulation of CDs by viruses may represent an effective and clever means of survival through the prolonged co-evolution of hosts and viruses. Targeting of CDs is anticipated to hinder the invasion of related viruses, modulate the body's immune system, and diminish the incidence of subsequent inflammation. They have become crucial for biomedical diagnosis, and some have been used as valuable tools for resisting viral infections. However, a summary of the structures and functions of CDs involved in viral infection is currently lacking. The development of drugs targeting these biological macromolecules is restricted both in terms of their availability and the number of compounds currently identified. This review provides a comprehensive analysis of the critical role of CD proteins in virus invasion and a list of relevant targeted antiviral agents, which will serve as a valuable reference for future research in this field.
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Affiliation(s)
- Youle Zheng
- National Reference Laboratory of Veterinary Drug Residues (HZAU), MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Jin Feng
- National Reference Laboratory of Veterinary Drug Residues (HZAU), MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Min Ling
- National Reference Laboratory of Veterinary Drug Residues (HZAU), MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Yixin Yu
- National Reference Laboratory of Veterinary Drug Residues (HZAU), MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Yanfei Tao
- National Reference Laboratory of Veterinary Drug Residues (HZAU), MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China
| | - Xu Wang
- National Reference Laboratory of Veterinary Drug Residues (HZAU), MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
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Villar LM, da Silva LL, do Lago BV, Pereira JG, Guimarães ACS, Mello FCDA, de Paula VS. Could Herpesviridae be the cause of severe acute hepatitis of unknown origin in children? Expert Rev Anti Infect Ther 2024; 22:5-17. [PMID: 38224018 DOI: 10.1080/14787210.2024.2304637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 01/09/2024] [Indexed: 01/16/2024]
Abstract
INTRODUCTION Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders. AREAS COVERED Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease. EXPERT OPINION Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.
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Affiliation(s)
- Livia Melo Villar
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Lucas Lima da Silva
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Barbara Vieira do Lago
- Viral Hepatitis Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Jessica Gonçalves Pereira
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Ana Carolina Silva Guimarães
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | | | - Vanessa Salete de Paula
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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Yarmohammadi H, Razavi A, Shahrabi Farahani M, Soltanipur M, Amini M. Characteristics of HHV-7 meningitis: a systematic review. J Neurol 2023; 270:5711-5718. [PMID: 37620518 DOI: 10.1007/s00415-023-11950-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/15/2023] [Accepted: 08/17/2023] [Indexed: 08/26/2023]
Abstract
There are limited data on HHV-7 meningitis and this systematic review used electronic search to gather pieces of evidence regarding its characteristics. Nine articles were included which three were case reports and the rest of the articles were retrospective studies. Altogether, 32 cases were described in the literature that 13 were females and 26 were aged less than 16 years old. The HHV-7 meningitis has been reported in any season, especially in winter. It affected both immunocompetent and immunocompromised individuals and mostly presented with fever and headache, however rash and seizure have also been documented. The CSF analysis in general showed an elevated range of cell count with lymphocytic predominance and normal to slightly elevated protein levels. Thirteen patients did not receive treatment for HHV-7 meningitis and full recovery was gained in the majority of cases after about 10 days. This review summarizes characteristics of HHV-7 meningitis in the literature, and yet epidemiological studies are needed to shed more light which eventually could be helpful for the diagnosis and management of this disease.
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Affiliation(s)
| | - Alireza Razavi
- Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | | | - Masood Soltanipur
- Medical Students Research Committee, Shahed University, Tehran, Iran
| | - Maryam Amini
- Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Shahed University, Tehran, Iran.
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Patrucco F, Curtoni A, Sidoti F, Zanotto E, Bondi A, Albera C, Boffini M, Cavallo R, Costa C, Solidoro P. Herpes Virus Infection in Lung Transplantation: Diagnosis, Treatment and Prevention Strategies. Viruses 2023; 15:2326. [PMID: 38140567 PMCID: PMC10747259 DOI: 10.3390/v15122326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 11/12/2023] [Accepted: 11/14/2023] [Indexed: 12/24/2023] Open
Abstract
Lung transplantation is an ultimate treatment option for some end-stage lung diseases; due to the intense immunosuppression needed to reduce the risk of developing acute and chronic allograft failure, infectious complications are highly incident. Viral infections represent nearly 30% of all infectious complications, with herpes viruses playing an important role in the development of acute and chronic diseases. Among them, cytomegalovirus (CMV) is a major cause of morbidity and mortality, being associated with an increased risk of chronic lung allograft failure. Epstein-Barr virus (EBV) is associated with transformation of infected B cells with the development of post-transplantation lymphoproliferative disorders (PTLDs). Similarly, herpes simplex virus (HSV), varicella zoster virus and human herpesviruses 6 and 7 can also be responsible for acute manifestations in lung transplant patients. During these last years, new, highly sensitive and specific diagnostic tests have been developed, and preventive and prophylactic strategies have been studied aiming to reduce and prevent the incidence of these viral infections. In this narrative review, we explore epidemiology, diagnosis and treatment options for more frequent herpes virus infections in lung transplant patients.
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Affiliation(s)
- Filippo Patrucco
- Respiratory Diseases Unit, Medical Department, AOU Maggiore della Carità di Novara, Corso Mazzini 18, 28100 Novara, Italy
| | - Antonio Curtoni
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Francesca Sidoti
- Division of Virology, Department of Public Health and Pediatrics, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Elisa Zanotto
- Division of Virology, Department of Public Health and Pediatrics, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Alessandro Bondi
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Carlo Albera
- Division of Respiratory Medicine, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Medical Sciences Department, University of Turin, 10126 Turin, Italy
| | - Massimo Boffini
- Cardiac Surgery Division, Surgical Sciences Department, AOU Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, Italy
| | - Rossana Cavallo
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Cristina Costa
- Division of Virology, Department of Public Health and Pediatrics, University of Turin, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
| | - Paolo Solidoro
- Division of Respiratory Medicine, Cardiovascular and Thoracic Department, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
- Medical Sciences Department, University of Turin, 10126 Turin, Italy
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Bruno F, Abondio P, Bruno R, Ceraudo L, Paparazzo E, Citrigno L, Luiselli D, Bruni AC, Passarino G, Colao R, Maletta R, Montesanto A. Alzheimer's disease as a viral disease: Revisiting the infectious hypothesis. Ageing Res Rev 2023; 91:102068. [PMID: 37704050 DOI: 10.1016/j.arr.2023.102068] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 09/05/2023] [Accepted: 09/07/2023] [Indexed: 09/15/2023]
Abstract
Alzheimer's disease (AD) represents the most frequent type of dementia in elderly people. Two major forms of the disease exist: sporadic - the causes of which have not yet been fully understood - and familial - inherited within families from generation to generation, with a clear autosomal dominant transmission of mutations in Presenilin 1 (PSEN1), 2 (PSEN2) or Amyloid Precursors Protein (APP) genes. The main hallmark of AD consists of extracellular deposits of amyloid-beta (Aβ) peptide and intracellular deposits of the hyperphosphorylated form of the tau protein. An ever-growing body of research supports the viral infectious hypothesis of sporadic forms of AD. In particular, it has been shown that several herpes viruses (i.e., HHV-1, HHV-2, HHV-3 or varicella zoster virus, HHV-4 or Epstein Barr virus, HHV-5 or cytomegalovirus, HHV-6A and B, HHV-7), flaviviruses (i.e., Zika virus, Dengue fever virus, Japanese encephalitis virus) as well as Human Immunodeficiency Virus (HIV), hepatitis viruses (HAV, HBV, HCV, HDV, HEV), SARS-CoV2, Ljungan virus (LV), Influenza A virus and Borna disease virus, could increase the risk of AD. Here, we summarized and discussed these results. Based on these findings, significant issues for future studies are also put forward.
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Affiliation(s)
- Francesco Bruno
- Regional Neurogenetic Centre (CRN), Department of Primary Care, Azienda Sanitaria Provinciale Di Catanzaro, Viale A. Perugini, 88046 Lamezia Terme, CZ, Italy; Association for Neurogenetic Research (ARN), Lamezia Terme, CZ, Italy
| | - Paolo Abondio
- Laboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy.
| | - Rossella Bruno
- Sudent at the Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88050 Catanzaro, Italy
| | - Leognano Ceraudo
- Sudent at the Department of Medical and Surgical Sciences, University of Parma, 43121 Parma, Italy
| | - Ersilia Paparazzo
- Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende 87036, Italy
| | - Luigi Citrigno
- National Research Council (CNR) - Institute for Biomedical Research and Innovation - (IRIB), 87050 Mangone, Cosenza, Italy
| | - Donata Luiselli
- Laboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy
| | - Amalia C Bruni
- Regional Neurogenetic Centre (CRN), Department of Primary Care, Azienda Sanitaria Provinciale Di Catanzaro, Viale A. Perugini, 88046 Lamezia Terme, CZ, Italy; Association for Neurogenetic Research (ARN), Lamezia Terme, CZ, Italy
| | - Giuseppe Passarino
- Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende 87036, Italy
| | - Rosanna Colao
- Regional Neurogenetic Centre (CRN), Department of Primary Care, Azienda Sanitaria Provinciale Di Catanzaro, Viale A. Perugini, 88046 Lamezia Terme, CZ, Italy
| | - Raffaele Maletta
- Regional Neurogenetic Centre (CRN), Department of Primary Care, Azienda Sanitaria Provinciale Di Catanzaro, Viale A. Perugini, 88046 Lamezia Terme, CZ, Italy; Association for Neurogenetic Research (ARN), Lamezia Terme, CZ, Italy
| | - Alberto Montesanto
- Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende 87036, Italy.
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Caroppo F, Gratteri F, Deotto ML, Salmaso R, Belloni Fortina A. An unusual skin eruption related to HHV-7 infection in a 14-year-old girl. J Paediatr Child Health 2023; 59:919-921. [PMID: 37066884 DOI: 10.1111/jpc.16410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/06/2023] [Indexed: 04/18/2023]
Affiliation(s)
- Francesca Caroppo
- Regional Center of Pediatric Dermatology - Department of Women's and Children's Health SDB, University of Padua, Padua, Italy
| | - Francesco Gratteri
- Regional Center of Pediatric Dermatology - Department of Women's and Children's Health SDB, University of Padua, Padua, Italy
| | - Maria Ludovica Deotto
- Regional Center of Pediatric Dermatology - Department of Women's and Children's Health SDB, University of Padua, Padua, Italy
| | - Roberto Salmaso
- Surgical Pathology and Cytopathology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy
| | - Anna Belloni Fortina
- Regional Center of Pediatric Dermatology - Department of Women's and Children's Health SDB, University of Padua, Padua, Italy
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Farahani MS, Yarmohammadi H, Motevalizadeh SA, Amini M. Meningitis associated with HHV-7 in an Iranian immunocompetent adolescent girl. J Neurovirol 2023; 29:346-349. [PMID: 37212976 PMCID: PMC10202047 DOI: 10.1007/s13365-023-01127-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/21/2023] [Accepted: 03/13/2023] [Indexed: 05/23/2023]
Abstract
There is limited literature regarding meningitis associated with HHV-7. This article reports an immunocompetent adolescent girl who developed fever, headache, and meningism which CSF molecular analysis with PCR was positive only for HHV-7. Interestingly, persistent cavum septum pellucidum and cavum vergae were observed on brain magnetic resonance imaging. The patient received antibiotics, dexamethasone, and acyclovir and then she gained full recovery. HHV-7 is a rare and yet possible pathogen in patients with meningitis, and this is the first described case report from Iran.
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Affiliation(s)
| | | | | | - Maryam Amini
- Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Shahed University, Tehran, Iran
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Miyase T, Mochizuki K, Kokuzawa S, Shiraki I, Murata K, Sakaguchi H. Vitreous Humor Positive for DNA of Human Herpesvirus 7 in Eye With Ocular Toxoplasmosis. Cureus 2023; 15:e41237. [PMID: 37529513 PMCID: PMC10387729 DOI: 10.7759/cureus.41237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2023] [Indexed: 08/03/2023] Open
Abstract
The aim of this article was to report our findings in a case of infectious uveitis in which the DNAs of both Toxoplasma gondii and human herpesvirus 7 (HHV-7) were detected in the vitreous fluid. A 31-year-old Brazilian man was examined in our hospital with a one-month history of blurred vision (20/40) in the right eye. He had been diagnosed with ocular toxoplasmosis of the right eye at nine years of age and has had repeated relapses. Because of the persistent vitreous opacities and refractoriness to acetylspiramycin and betamethasone, pars plana vitrectomy was performed. Multiplex PCR of the vitreous sample demonstrated the DNAs for both T. gondii and HHV-7. Trimethoprim/sulfamethoxazole with prednisone was prescribed. Six months after the beginning of the therapy, a resolution of the retinochoroiditis was found and the vision recovered to 20/25. Two months later, we performed a pars plana vitrectomy for an epiretinal membrane. The DNAs of both T. gondii and HHV-7 were not detected in the vitreous fluid and the epiretinal membrane. After continued treatment, the best-corrected visual acuity (BCVA) in the right eye improved to 20/16 and the metamorphopsia was reduced. It is inferred from this work that HHV-7 reactivation can activate refractory infectious uveitis in patients with chronic ocular toxoplasmosis.
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Affiliation(s)
- Taishi Miyase
- Ophthalmology, Gifu University, Gifu, JPN
- Ophthalmology, Ogaki Municipal Hospital, Ogaki, JPN
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Syndrome of Transient Headache and Neurologic Deficits with Cerebrospinal Fluid Lymphocytosis (HaNDL): HHV-7 Finding in Cerebrospinal Fluid Challenges Diagnostic Criteria. Pathogens 2023; 12:pathogens12030476. [PMID: 36986398 PMCID: PMC10051435 DOI: 10.3390/pathogens12030476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/14/2023] [Accepted: 03/16/2023] [Indexed: 03/22/2023] Open
Abstract
The syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a rare, self-limiting condition with severe headaches combined with neurological symptoms. However, evidence-based recommendations on diagnostics and treatments are unavailable due to the condition’s rarity and unknown pathophysiology. A young man experiencing severe headache attacks fulfilled the HaNDL diagnostic criteria according to the third edition of the International Classification of Headache Disorders (ICHD-3). We present the dynamics of cerebrospinal fluid (CSF) biomarkers related to low human herpesvirus 7 (HHV-7) load and anti-inflammatory treatment outcomes. Low HHV-7 load may be an immunological trigger of HaNDL, such that elevated levels of CSF- chemokine (C-X-C motif) ligand 13 open a new way to interpret the role of B cells in HaNDL pathogenesis. We discuss the diagnostic challenge of HaNDL, according to the ICHD-3, in the case of pathogen presence at low load in CSF.
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Anterior Uveitis Associated with Human Herpesvirus 7 Infection Diagnosed by Multiplex Polymerase Chain Reaction Assay: A Case Report. Ocul Immunol Inflamm 2023; 31:474-476. [PMID: 35201962 DOI: 10.1080/09273948.2022.2032191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Herpetic anterior uveitis (AU) is usually caused by the herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Herein, we report a case of herpetic AU associated with human herpesvirus 7 (HHV-7) infection. STUDY DESIGN A case report. CASE PRESENTATION A 49-year-old female patient presented with complaints of blurred vision and hyperemia in the right eye. Slit-lamp examination revealed bilateral fine and a few small white keratic precipitates (KPs), Descemet membrane folds in the right eye, and severe and mild cellular infiltration in the anterior chamber of the right and left eye, respectively. HHV-7 viral DNA was detected by a polymerase chain reaction assay of an aqueous humor sample. The AU improved significantly with topical steroids. CONCLUSION We report a rare case of herpetic AU characterized by fine and small white KPs in which only HHV-7 DNA was detected in the aqueous humor.
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Hamada N, Shigeishi H, Oka I, Sasaki M, Kitasaki H, Nakamura M, Yano K, Wu CH, Kaneyasu Y, Maehara T, Sugiyama M, Ohta K. Associations between Oral Human Herpesvirus-6 and -7 and Periodontal Conditions in Older Adults. Life (Basel) 2023; 13:life13020324. [PMID: 36836681 PMCID: PMC9965650 DOI: 10.3390/life13020324] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/17/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND The associations between oral human herpesvirus-6 (HHV-6) and HHV-7, periodontal conditions, and lifestyle-related diseases, such as hypertension, diabetes, and dyslipidemia, have not been fully investigated in older adults. METHODS Seventy-four older patients who visited Hiroshima University Hospital were enrolled. Tongue swab samples were employed, and a real-time polymerase chain reaction was performed to detect HHV-6 and HHV-7 DNA. Dental plaque accumulation, probing pocket depth, and bleeding on probing (BOP) (i.e., a sign of periodontal inflammation) were examined. The periodontal inflamed surface area (PISA) value (i.e., an indicator of the severity of periodontitis) was also examined. RESULTS Of the 74 participants, one participant (1.4%) was HHV-6 DNA-positive and 36 participants (48.6%) were HHV-7 DNA-positive. A significant association between HHV-7 DNA and probing depth was found (p = 0.04). The HHV-7 DNA-positive participants had a higher positive rate of a ≥6-mm periodontal pocket with BOP (25.0%) than the HHV-7 DNA-negative participants (7.9%). Additionally, the HHV-7 DNA-positive participants had a higher PISA value than the HHV-7 DNA-negative participants. However, there was no significant association between HHV-7 and the PISA value (p = 0.82). No significant association was found between HHV-7 and lifestyle-related diseases (p > 0.05). CONCLUSIONS Oral HHV-7 infection is associated with a deep periodontal pocket.
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Michelerio A, Tchich A, Vassallo C, Brazzelli V. Atypical exanthem with acral involvement in adult patients associated with human herpesvirus 7 active replication: A case series. Front Med (Lausanne) 2023; 10:1144856. [PMID: 37122320 PMCID: PMC10140440 DOI: 10.3389/fmed.2023.1144856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/16/2023] [Indexed: 05/02/2023] Open
Abstract
An "atypical exanthem" (AE) is an eruptive skin eruption that differs in morphology and etiology from classical exanthems and is often a reason for urgent medical evaluation. The most frequent cause of AEs is a viral infection, but an accurate etiology cannot be established basing on the sole clinical features. Human herpesviruses (HHV) have been often suspected as etiologic agents or cofactors in atypical rashes. We performed a retrospective analysis of adult patients presenting an atypical exanthem associated with HHV-7 active replication in our center. The charts of patients were reviewed and the demographic, clinical and laboratory data collected. Nine patients (six males and three females) were included in the study, with a mean age of 43 years for men and of 26 years for women. All patients presented active HHV-7 replication in plasma during the rash, which turned negative after the exanthem resolved. The exanthem displayed a maculopapular pattern involving the trunk, limbs and, notably, the acral regions, in six patients. In three cases the exanthem was confined to only the acral sites. In most cases, there was no fever and the inflammatory indices remained unchanged. Antihistamines, topical and systemic corticosteroids were used as treatment, with excellent symptom control. We propose adding skin manifestation associated with HHV-7 to the concept of atypical exanthems, in particular those localized to the acral regions.
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Affiliation(s)
- Andrea Michelerio
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Adi Tchich
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Camilla Vassallo
- Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Valeria Brazzelli
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- Dermatology Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- *Correspondence: Valeria Brazzelli,
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Early Phase Increase in Serum TIMP-1 in Patients with Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion. CHILDREN (BASEL, SWITZERLAND) 2022; 10:children10010078. [PMID: 36670630 PMCID: PMC9857315 DOI: 10.3390/children10010078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 12/26/2022] [Accepted: 12/28/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most frequent subtype of acute encephalopathy syndrome among Japanese children. Exanthem subitum is the most common causative infectious disease of AESD. We herein retrospectively analyzed serum and cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase-9 (MMP-9), tissue inhibitor matrix metalloproteinase-1 (TIMP-1), and seven cytokines in patients with AESD or prolonged febrile seizure (FS) to assess the pathophysiology of AESD and detect biomarkers for diagnosing AESD in the early phase. METHODS Serum and CSF samples were obtained from 17 patients with AESD (1st seizure phase group, n = 7; 2nd seizure phase group, n = 10) and 8 with FS. The concentrations of MMP-9, TIMP-1, and seven cytokines were measured by enzyme-linked immunosorbent assays or cytometric bead arrays. RESULTS Serum concentrations of TIMP-1 were significantly higher in the 1st seizure phase group than in the 2nd seizure phase group. No significant differences were observed in serum concentrations of MMP-9 or the MMP-9/TIMP-1 ratio. CONCLUSIONS The MMP-9-independent increase in circulating TIMP-1 concentrations observed in the present study may be associated with the pathophysiology of AESD in the 1st seizure phase.
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15
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Carneiro VCDS, Pereira JG, de Paula VS. Family Herpesviridae and neuroinfections: current status and research in progress. Mem Inst Oswaldo Cruz 2022; 117:e220200. [PMID: 36417627 PMCID: PMC9677594 DOI: 10.1590/0074-02760220200] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/10/2022] [Indexed: 11/22/2022] Open
Abstract
This article addresses the relationship between human herpesviruses (HHVs) and neuroinfections. Alphaherpesviruses, betaherpesviruses and gammaherpesviruses are neurotropic viruses that establish latency and exhibit reactivation capacity. Encephalitis and meningitis are common in cases of HHV. The condition promoted by HHV infection is a purported trigger for certain neurodegenerative diseases. Ongoing studies have identified an association between HSV-1 and the occurrence of Alzheimer's disease, multiple sclerosis and infections by HHV-6 and Epstein-Barr virus. In this review, we highlight the importance of research investigating the role of herpesviruses in the pathogenesis of diseases that affect the nervous system and describe other studies in progress.
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Affiliation(s)
| | | | - Vanessa Salete de Paula
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Virologia Molecular, Rio de Janeiro, RJ, Brasil,+ Corresponding author:
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16
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Mardanly SS, Mardanly SG, Kazakov AA, Demkin VV, Zatevalov AM, Mironov AY. Development of a PCR assay for the detection of human herpes virus type 7. Klin Lab Diagn 2022; 67:658-662. [PMID: 36398775 DOI: 10.51620/0869-2084-2022-67-11-658-662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
A PCR assay has been developed to identify the DNA of the human herpes virus type 7. The search and selection of conserved regions was carried out by comparing the whole genome nucleotide sequences of HHV-7. A fragment duplicated in the HHV-7 genomes was chosen as a target for amplification. The performance of the assay was tested on a synthetic matrix and clinical samples. The developed assay has high sensitivity and specificity and showed good efficiency in detecting HHV-7 DNA in clinical samples.
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Affiliation(s)
| | | | - A A Kazakov
- Federal State Budgetary Institution "Institute of Molecular Genetics, National Research Center "Kurchatov Institute""
| | - V V Demkin
- Federal State Budgetary Institution "Institute of Molecular Genetics, National Research Center "Kurchatov Institute""
| | - A M Zatevalov
- G.N. Gabrichevsky research institute for epidemiology and microbiology of the Rospotrebnadzor
| | - A Yu Mironov
- G.N. Gabrichevsky research institute for epidemiology and microbiology of the Rospotrebnadzor
- Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies of the FMBA of Russia
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17
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Ciccarese G, Parodi A, Drago F. The significance of investigating clinical, histopathologic and virological features in pityriasis rosea and pityriasis rosea-like eruptions following COVID-19 vaccinations. Dermatol Ther 2022; 35:e15601. [PMID: 35622411 PMCID: PMC9347716 DOI: 10.1111/dth.15601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 04/26/2022] [Accepted: 04/27/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Giulia Ciccarese
- Dermatology Unit, Policlinico San Martino, Largo R. Benzi, 10, 16132, Genoa, Italy
| | - Aurora Parodi
- Dermatology Unit, Policlinico San Martino, Largo R. Benzi, 10, 16132, Genoa, Italy.,Section of Dermatology, Department of Health Sciences, University of Genoa, Via Pastore, 1, 16132, Genoa, Italy
| | - Francesco Drago
- Dermatology Unit, Policlinico San Martino, Largo R. Benzi, 10, 16132, Genoa, Italy
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18
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Oumarou Hama H, Aboudharam G, Barbieri R, Lepidi H, Drancourt M. Immunohistochemical diagnosis of human infectious diseases: a review. Diagn Pathol 2022; 17:17. [PMID: 35094696 PMCID: PMC8801197 DOI: 10.1186/s13000-022-01197-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 01/18/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Immunohistochemistry (IHC) using monoclonal and polyclonal antibodies is a useful diagnostic method for detecting pathogen antigens in fixed tissues, complementing the direct diagnosis of infectious diseases by PCR and culture on fresh tissues. It was first implemented in a seminal publication by Albert Coons in 1941. MAIN BODY Of 14,198 publications retrieved from the PubMed, Google, Google Scholar and Science Direct databases up to December 2021, 230 were selected for a review of IHC techniques, protocols and results. The methodological evolutions of IHC and its application to the diagnosis of infectious diseases, more specifically lice-borne diseases, sexually transmitted diseases and skin infections, were critically examined. A total of 59 different pathogens have been detected once in 22 different tissues and organs; and yet non-cultured, fastidious and intracellular pathogens accounted for the vast majority of pathogens detected by IHC. Auto-IHC, incorporating patient serum as the primary antibody, applied to diseased heart valves surgically collected from blood culture-negative endocarditis patients, detected unidentified Gram-positive cocci and microorganisms which were subsequently identified as Coxiella burnetii, Bartonella quintana, Bartonella henselae and Tropheryma whipplei. The application of IHC to ancient tissues dated between the ends of the Ptolemaic period to over 70 years ago, have also contributed to paleomicrobiology diagnoses. CONCLUSION IHC plays an important role in diagnostic of infectious diseases in tissue samples. Paleo-auto-IHC derived from auto-IHC, is under development for detecting non-identified pathogens from ancient specimens.
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Affiliation(s)
- Hamadou Oumarou Hama
- IHU Méditerranée Infection, Marseille, France
- Aix-Marseille-Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France
| | - Gérard Aboudharam
- Aix-Marseille-Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France
- Aix-Marseille-Univ., Ecole de Médecine Dentaire, Marseille, France
| | - Rémi Barbieri
- IHU Méditerranée Infection, Marseille, France
- Aix-Marseille-Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France
| | - Hubert Lepidi
- Aix-Marseille-Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France
- Laboratoire d'Histologie, Faculté de Médecine, Université de la Méditerranée, Marseille, France
| | - Michel Drancourt
- IHU Méditerranée Infection, Marseille, France.
- Aix-Marseille-Univ., IRD, MEPHI, IHU Méditerranée Infection, Marseille, France.
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19
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Ogawa H, Fujikura D, Namba H, Yamashita N, Honda T, Yamada M. Nectin-2 Acts as a Viral Entry Mediated Molecule That Binds to Human Herpesvirus 6B Glycoprotein B. Viruses 2022; 14:v14010160. [PMID: 35062364 PMCID: PMC8779676 DOI: 10.3390/v14010160] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 01/06/2022] [Accepted: 01/13/2022] [Indexed: 02/01/2023] Open
Abstract
Human herpesvirus 6B (HHV-6B) is a T-lymphotropic virus and the etiological agent of exanthem subitum. HHV-6B is present in a latent or persistent form after primary infection and is produced in the salivary glands or transmitted to this organ. Infected individuals continue to secrete the virus in their saliva, which is thus considered a source for virus transmission. HHV-6B primarily propagates in T cells because its entry receptor, CD134, is mainly expressed by activated T cells. The virus then spreads to the host’s organs, including the salivary glands, nervous system, and liver. However, CD134 expression is not detected in these organs. Therefore, HHV-6B may be entering cells via a currently unidentified cell surface molecule, but the mechanisms for this have not yet been investigated. In this study, we investigated a CD134-independent virus entry mechanism in the parotid-derived cell line HSY. First, we confirmed viral infection in CD134-membrane unanchored HSY cells. We then determined that nectin cell adhesion molecule 2 (nectin-2) mediated virus entry and that HHV-6B-insensitive T-cells transduced with nectin-2 were transformed into virus-permissive cells. We also found that virus entry was significantly reduced in nectin-2 knockout parotid-derived cells. Furthermore, we showed that HHV-6B glycoprotein B (gB) interacted with the nectin-2 V-set domain. The results suggest that nectin-2 acts as an HHV-6B entry-mediated protein.
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Affiliation(s)
- Hirohito Ogawa
- Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; (H.N.); (N.Y.); (T.H.)
- Correspondence: (H.O.); (M.Y.)
| | - Daisuke Fujikura
- School of Veterinary Medicine, Kitasato University, Higashi 23-35-1, Towada 034-8628, Japan;
| | - Hikaru Namba
- Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; (H.N.); (N.Y.); (T.H.)
| | - Nobuko Yamashita
- Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; (H.N.); (N.Y.); (T.H.)
| | - Tomoyuki Honda
- Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; (H.N.); (N.Y.); (T.H.)
| | - Masao Yamada
- Department of Virology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; (H.N.); (N.Y.); (T.H.)
- Correspondence: (H.O.); (M.Y.)
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20
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Verzosa AL, McGeever LA, Bhark SJ, Delgado T, Salazar N, Sanchez EL. Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms. Front Immunol 2021; 12:644664. [PMID: 34135889 PMCID: PMC8201405 DOI: 10.3389/fimmu.2021.644664] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 05/07/2021] [Indexed: 12/13/2022] Open
Abstract
Alphaherpesviruses (α-HV) are a large family of double-stranded DNA viruses which cause many human and animal diseases. There are three human α-HVs: Herpes Simplex Viruses (HSV-1 and HSV-2) and Varicella Zoster Virus (VZV). All α-HV have evolved multiple strategies to suppress or exploit host cell innate immune signaling pathways to aid in their infections. All α-HVs initially infect epithelial cells (primary site of infection), and later spread to infect innervating sensory neurons. As with all herpesviruses, α-HVs have both a lytic (productive) and latent (dormant) stage of infection. During the lytic stage, the virus rapidly replicates in epithelial cells before it is cleared by the immune system. In contrast, latent infection in host neurons is a life-long infection. Upon infection of mucosal epithelial cells, herpesviruses immediately employ a variety of cellular mechanisms to evade host detection during active replication. Next, infectious viral progeny bud from infected cells and fuse to neuronal axonal terminals. Here, the nucleocapsid is transported via sensory neuron axons to the ganglion cell body, where latency is established until viral reactivation. This review will primarily focus on how HSV-1 induces various innate immune responses, including host cell recognition of viral constituents by pattern-recognition receptors (PRRs), induction of IFN-mediated immune responses involving toll-like receptor (TLR) signaling pathways, and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING). This review focuses on these pathways along with other mechanisms including autophagy and the complement system. We will summarize and discuss recent evidence which has revealed how HSV-1 is able to manipulate and evade host antiviral innate immune responses both in neuronal (sensory neurons of the trigeminal ganglia) and non-neuronal (epithelial) cells. Understanding the innate immune response mechanisms triggered by HSV-1 infection, and the mechanisms of innate immune evasion, will impact the development of future therapeutic treatments.
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Affiliation(s)
- Amanda L Verzosa
- Biology Department, College of Science and Engineering, San Francisco State University, San Francisco, CA, United States
| | - Lea A McGeever
- Biology Department, College of Science and Engineering, San Francisco State University, San Francisco, CA, United States
| | - Shun-Je Bhark
- Biology Department, Seattle Pacific University, Seattle, WA, United States
| | - Tracie Delgado
- Biology Department, Seattle Pacific University, Seattle, WA, United States
| | - Nicole Salazar
- Biology Department, College of Science and Engineering, San Francisco State University, San Francisco, CA, United States
| | - Erica L Sanchez
- Biology Department, College of Science and Engineering, San Francisco State University, San Francisco, CA, United States
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21
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Foiadelli T, Rossi V, Paolucci S, Rovida F, Novazzi F, Orsini A, Brambilla I, Marseglia GL, Baldanti F, Savasta S. Human Herpes Virus 7-related encephalopathy in children. ACTA BIO-MEDICA : ATENEI PARMENSIS 2021; 92:e2021415. [PMID: 35441609 PMCID: PMC9179060 DOI: 10.23750/abm.v92is4.12664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/27/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND Primary HHV7 infection is almost ubiquitous, and it can present as exanthema subitem. Little is known on the clinical relevance of HHV7 neuroinvasion in immunocompetent children. METHODS We describe 12 patients (median age 9.45 years, 50% males) with acute encephalopathy and active HHV7 infection. In all patients, HHV7-DNA was detected on cerebrospinal fluid (CSF) by RT-PCR. RESULTS 7/12 patients had meningoencephalitis (two with ADEM and one with MOG antibody-associated CIS); 5/12 showed acute neuropsychiatric symptoms. EEG showed anomalies exclusively in patients with meningoencephalitis. Six patients had RMN anomalies. CSF HHV7 copies ranged between 20 and 3,500 copies/mL (median 66 copies/mL) and mean HHV7 CSF/blood ratio was 0.75. Outcome was favorable in all children, although 3/12 had minor neurobehavioral sequelae. Mean follow-up period of 5.2 months. CONCLUSIONS HHV7 can determine neuroinvasion in immunocompetent children, leading to acute encephalopathy. Blood-brain barrier damage and high CSF/blood viral copies ratio correlated with a more severe presentation. We speculate on the importance of immune-mediated mechanisms in provoking clinical features.
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Affiliation(s)
- Thomas Foiadelli
- Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Virginia Rossi
- Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Stefania Paolucci
- Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Francesca Rovida
- Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Federica Novazzi
- Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Alessandro Orsini
- Pediatric Neurology, Pediatric University Department, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Italy
| | - Ilaria Brambilla
- Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Gian Luigi Marseglia
- Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Fausto Baldanti
- Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy, Molecular Virology Unit, Department of Diagnostic Medicine, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
| | - Salvatore Savasta
- Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, Pavia, Italy
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22
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Inflammatory Cytokine-Producing Cells and Inflammation Markers in the Synovium of Osteoarthritis Patients Evidenced in Human Herpesvirus 7 Infection. Int J Mol Sci 2020; 21:ijms21176004. [PMID: 32825448 PMCID: PMC7504613 DOI: 10.3390/ijms21176004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/18/2020] [Accepted: 08/19/2020] [Indexed: 12/11/2022] Open
Abstract
A direct association between joint inflammation and the progression of osteoarthritis (OA) has been proposed, and synovitis is considered a powerful driver of the disease. Among infections implicated in the development of joint disease, human herpesvirus 7 (HHV-7) infection remains poorly characterized. Therefore, we assessed synovitis in OA patients; determined the occurrence and distribution of the HHV-7 antigen within the synovial membrane of OA-affected subjects; and correlated plasma levels of the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin-6 (IL-6), and TNF expressed locally within lesioned synovial tissues with HHV-7 observations, suggesting differences in persistent latent and active infection. Synovial HHV-7, CD4, CD68, and TNF antigens were detected immunohistochemically. The plasma levels of TNF and IL-6 were measured by an enzyme-linked immunosorbent assay. Our findings confirm the presence of persistent HHV-7 infection in 81.5% and reactivation in 20.5% of patients. In 35.2% of patients, virus-specific DNA was extracted from synovial membrane tissue samples. We evidenced the absence of histopathologically detectable synovitis and low-grade changes in the majority of OA patients enrolled in the study, in both HHV-7 PCR+ and HHV-7 PCR‒ groups. The number of synovial CD4-positive cells in the HHV-7 polymerase chain reaction (PCR)+ group was significantly higher than that in the HHV-7 PCR‒ group. CD4- and CD68-positive cells were differently distributed in both HHV-7 PCR+ and HHV-7 PCR‒ groups, as well as in latent and active HHV-7 infection. The number of TNF+ and HHV-7+ lymphocytes, as well as HHV-7+ vascular endothelial cells, was strongly correlated. Vascular endothelial cells, especially in the case of infection reactivation, appeared vulnerable. The balance between virus latency and reactivation is a long-term relationship between the host and infectious agent, and the immune system appears to be involved in displaying overreaction when a shift in the established equilibrium develops.
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Abstract
During local small measles outbreak in Japan, 3 adolescents with febrile skin rash suspected as having measles were diagnosed with primary human herpesvirus (HHV)-7 infection. Primary HHV-7 infection can cause exanthem subitum in not only young children but also adolescents. HHV-7 should be considered as a possible causative agent for adolescent febrile skin rash during the measles outbreak.
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Current understanding of human herpesvirus 6 (HHV-6) chromosomal integration. Antiviral Res 2020; 176:104720. [PMID: 32044155 DOI: 10.1016/j.antiviral.2020.104720] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 01/21/2020] [Accepted: 01/23/2020] [Indexed: 12/12/2022]
Abstract
Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are members of the genus Roseolovirus in the Betaherpesvirinae subfamily. HHV-6B infects humans in the first years of life, has a seroprevalence of more than 90% and causes Roseola Infantum, but less is known about HHV-6A. While most other herpesviruses maintain their latent genome as a circular episome, HHV-6A and HHV-6B (HHV-6A/B) have been shown to integrate their genome into the telomeres of infected cells. HHV-6A/B can also integrate into the chromosomes of germ cells, resulting in individuals carrying a copy of the virus genome in every nucleated cell of their bodies. This review highlights our current understanding of HHV-6A/B integration and reactivation as well as aspects that should be addressed in the future of this relatively young research area. It forms part of an online symposium on the prevention and therapy of DNA virus infections, dedicated to the memory of Mark Prichard.
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25
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Human inborn errors of immunity to herpes viruses. Curr Opin Immunol 2020; 62:106-122. [PMID: 32014647 DOI: 10.1016/j.coi.2020.01.004] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 12/16/2019] [Accepted: 01/07/2020] [Indexed: 12/16/2022]
Abstract
Infections with any of the nine human herpes viruses (HHV) can be asymptomatic or life-threatening. The study of patients with severe diseases caused by HHVs, in the absence of overt acquired immunodeficiency, has led to the discovery or diagnosis of various inborn errors of immunity. The related inborn errors of adaptive immunity disrupt α/β T-cell rather than B-cell immunity. Affected patients typically develop HHV infections in the context of other infectious diseases. However, this is not always the case, as illustrated by inborn errors of SAP-dependent T-cell immunity to EBV-infected B cells. The related inborn errors of innate immunity disrupt leukocytes other than T and B cells, non-hematopoietic cells, or both. Patients typically develop only a single type of infection due to HHV, although, again, this is not always the case, as illustrated by inborn errors of TLR3 immunity resulting in HSV1 encephalitis in some patients and influenza pneumonitis in others. Most severe HHV infections in otherwise healthy patients remains unexplained. The forward human genetic dissection of isolated and syndromic HHV-driven illnesses will establish the molecular and cellular basis of protective immunity to HHVs, paving the way for novel diagnosis and management strategies.
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26
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Puglia ALP, Peigo MDF, Bomfim FRC, Thomasini RL. Development of an enzyme-linked immunosorbent assay for diagnosis of human herpesvirus-7 infection. Rev Soc Bras Med Trop 2020; 53:e20190181. [PMID: 32187333 PMCID: PMC7094058 DOI: 10.1590/0037-8682-0181-2019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 11/26/2019] [Indexed: 11/22/2022] Open
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Denner J, Bigley TM, Phan TL, Zimmermann C, Zhou X, Kaufer BB. Comparative Analysis of Roseoloviruses in Humans, Pigs, Mice, and Other Species. Viruses 2019; 11:E1108. [PMID: 31801268 PMCID: PMC6949924 DOI: 10.3390/v11121108] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 11/13/2019] [Accepted: 11/27/2019] [Indexed: 12/11/2022] Open
Abstract
Viruses of the genus Roseolovirus belong to the subfamily Betaherpesvirinae, family Herpesviridae. Roseoloviruses have been studied in humans, mice and pigs, but they are likely also present in other species. This is the first comparative analysis of roseoloviruses in humans and animals. The human roseoloviruses human herpesvirus 6A (HHV-6A), 6B (HHV-6B), and 7 (HHV-7) are relatively well characterized. In contrast, little is known about the murine roseolovirus (MRV), also known as murine thymic virus (MTV) or murine thymic lymphotrophic virus (MTLV), and the porcine roseolovirus (PRV), initially incorrectly named porcine cytomegalovirus (PCMV). Human roseoloviruses have gained attention because they can cause severe diseases including encephalitis in immunocompromised transplant and AIDS patients and febrile seizures in infants. They have been linked to a number of neurological diseases in the immunocompetent including multiple sclerosis (MS) and Alzheimer's. However, to prove the causality in the latter disease associations is challenging due to the high prevalence of these viruses in the human population. PCMV/PRV has attracted attention because it may be transmitted and pose a risk in xenotransplantation, e.g., the transplantation of pig organs into humans. Most importantly, all roseoloviruses are immunosuppressive, the humoral and cellular immune responses against these viruses are not well studied and vaccines as well as effective antivirals are not available.
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Affiliation(s)
- Joachim Denner
- Robert Koch Institute, Robert Koch Fellow, 13352 Berlin, Germany
| | - Tarin M. Bigley
- Division of Rheumatology, Department. of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Tuan L. Phan
- Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70118, USA;
- HHV-6 Foundation, Santa Barbara, CA 93108, USA
| | - Cosima Zimmermann
- Institute of Virology, Freie Universität Berlin, 14163 Berlin, Germany;
| | - Xiaofeng Zhou
- Division of Pulmonary and Critical Care Medicine, Department. of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
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Mardanly SG, Arsenyeva VA, Amelina EA, Avdonina AS, Mardanly SS. [First results of application of an enzyme immunoassay in the serological diagnostics of infection caused by herpesvirus type 7.]. Klin Lab Diagn 2019; 64:530-535. [PMID: 31610104 DOI: 10.18821/0869-2084-2019-64-9-530-535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 08/22/2019] [Indexed: 11/17/2022]
Abstract
HHV-7 (Human Herpes virus type 7) is a relatively recently discovered, ubiquitous beta herpes virus. In Russia, the diagnosis of HHV-7 infection is carried out by PCR, which determines the DNA in serum or plasma, if there are clinical indications. Laboratory serological tests for HHV-7 are not performed. Currently, in the scientific literature, information on clinical studies of HHV-7 infection, its epidemiology, and its role in the etiopathogenesis of various diseases is insufficient. This article presents the results of the development of a test kit "ELISA-HHV-7-IgG", designed to detect specific IgG to HHV-7 by enzyme-linked immunosorbent assay (ELISA). Studies of the sensitivity and specificity of the developed test kit, including potential cross-reactive samples positive for other herpesvirus infections, were carried out. In the context of serological diagnostics, we studied samples of the sera of children (n = 167) and old people (n = 238) for the presence of IgG to HHV-7 with confirmation of the results in the indirect immunofluorescence reaction and the immune blotting reaction. The research results are evidence of the possibility of using the developed test kit for serological diagnosis of HHV-7 infection.
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Affiliation(s)
- S G Mardanly
- CJSC "EKOlab", 142530, Elektrogorsk, Moscow region.,State educational institution of higher education of the Moscow region, State Humanitarian University of Technology "GGTU", 142611, Orekhovo-Zuyevo, Moscow region
| | | | - E A Amelina
- CJSC "EKOlab", 142530, Elektrogorsk, Moscow region
| | - A S Avdonina
- CJSC "EKOlab", 142530, Elektrogorsk, Moscow region
| | - S S Mardanly
- CJSC "EKOlab", 142530, Elektrogorsk, Moscow region.,National Research Center оf Epidemiology and Microbiology named after honorary academician N.F. Gamalei of the Ministry of Health of the Russian Federation, 123098, Moscow
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Houldcroft CJ. Human Herpesvirus Sequencing in the Genomic Era: The Growing Ranks of the Herpetic Legion. Pathogens 2019; 8:E186. [PMID: 31614759 PMCID: PMC6963362 DOI: 10.3390/pathogens8040186] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/10/2019] [Accepted: 10/11/2019] [Indexed: 12/19/2022] Open
Abstract
The nine human herpesviruses are some of the most ubiquitous pathogens worldwide, causing life-long latent infection in a variety of different tissues. Human herpesviruses range from mild childhood infections to known tumour viruses and 'trolls of transplantation'. Epstein-Barr virus was the first human herpesvirus to have its whole genome sequenced; GenBank now includes thousands of herpesvirus genomes. This review will cover some of the recent advances in our understanding of herpesvirus diversity and disease that have come about as a result of new sequencing technologies, such as target enrichment and long-read sequencing. It will also look at the problem of resolving mixed-genotype infections, whether with short or long-read sequencing methods; and conclude with some thoughts on the future of the field as herpesvirus population genomics becomes a reality.
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Affiliation(s)
- Charlotte J Houldcroft
- Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambs CB2 0QQ UK.
- Parasites and Microbes, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambs CB10 1SA, UK.
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Kourieh A, Gheit T, Tommasino M, Dalstein V, Clifford GM, Lacau St Guily J, Clavel C, Franceschi S, Combes JD. Prevalence of human herpesviruses infections in nonmalignant tonsils: The SPLIT study. J Med Virol 2019; 91:687-697. [PMID: 30318627 DOI: 10.1002/jmv.25338] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/09/2018] [Indexed: 01/25/2023]
Abstract
OBJECTIVE To assess the prevalence of all known human herpesviruses (HHV) in tonsils of an age-stratified large sample of immunocompetent children and adults. METHODS Patients undergoing tonsillectomy for benign indications were recruited in 19 French hospitals. After resection, the entire outer surfaces of right and left half tonsils were extensively brushed. A highly sensitive species-specific multiplex assay was used to detect herpes simplex virus 1 (HSV1), HSV2, Epstein-Barr virus (EBV; types 1 and 2), and human cytomegalovirus (CMV) DNA in 688, as well as varicella zoster virus (VZV), HHV6A, HHV6B, HHV7, and Kaposi's sarcoma-associated herpesvirus (KSHV) DNA in a subset of 440 tonsil brushings. RESULTS Overall 85% of tonsil brushing samples were infected with at least one HHV species. HHV7 and EBV were the most prevalent (≈70%), followed by HHV6B (≈50%), HSV1, CMV, VZV (≈2%), and KSHV and HSV2 (<1%), while HHV6A was not detected. EBV prevalence was significantly higher in adults than in children, whereas it was opposite for HHV6B and VZV. No difference in HHV prevalence was observed by sex. In multivariate analysis, EBV detection was associated with age greater than or equal to 15 years (prevalence ratio [PR] = 1.8; 95% confidence interval [CI]: 1.5-2.3) and marginally with tobacco smoking (PR = 1.2; 95% CI: 1.1-1.3). CONCLUSION Differing patterns of HHV infection in tonsils in a large age-stratified population were described. This study is by far the largest available and shows that EBV, HHV6B, and HHV7 are commonly detected in the tonsils in both men and women, in contrast to other HHVs.
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Affiliation(s)
- Aboud Kourieh
- International Agency for Research on Cancer, Lyon, France
| | - Tarik Gheit
- International Agency for Research on Cancer, Lyon, France
| | | | - Véronique Dalstein
- CHU Reims, Hôpital Maison Blanche, Laboratoire Biopathologie, Reims, France
- INSERM, UMR-S 1250, Université de Reims Champagne-Ardenne, Reims, France
| | | | - Jean Lacau St Guily
- Department of Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine, Sorbonne University and Tenon Hospital, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Christine Clavel
- CHU Reims, Hôpital Maison Blanche, Laboratoire Biopathologie, Reims, France
- INSERM, UMR-S 1250, Université de Reims Champagne-Ardenne, Reims, France
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Khairallah M, Mahendradas P, Curi A, Khochtali S, Cunningham ET. Emerging Viral Infections Causing Anterior Uveitis. Ocul Immunol Inflamm 2019; 27:219-228. [PMID: 30794475 DOI: 10.1080/09273948.2018.1562080] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE To review the systemic and ocular manifestations of specific emergent viral infectious diseases relevant to the ophthalmologist with particular emphasis on anterior uveitis Methods: Review of literature. RESULTS Arboviral diseases are among the most important emergent and resurgent human infections, occurring mostly in tropical and subtropical zones, but appearing in virtually all regions of the world as a result of climate change, travel, and globalization. Arboviral infections are transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. Systemic disease may range from asymptomatic to life-threatening. A wide variety of ocular manifestations, including uveitis, has been reported in association with these emerging viral diseases. Numerous viruses other than arboviruses also have been recently recognized as a potential cause of uveitis. CONCLUSIONS Proper clinical diagnosis of any emerging infectious disease is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by detection of virus-specific DNA or antivirus antibodies in serum.
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Affiliation(s)
- Moncef Khairallah
- a Department of Ophthalmology, Fattouma Bourguiba University Hospital, Faculty of Medicine , University of Monastir , Monastir , Tunisia
| | | | - Andre Curi
- c Research Laboratory of Infectious Diseases in Ophthalmology, National Institute of Infectious Diseases , Oswaldo Cruz Foundation , Rio de Janeiro , Brazil
| | - Sana Khochtali
- a Department of Ophthalmology, Fattouma Bourguiba University Hospital, Faculty of Medicine , University of Monastir , Monastir , Tunisia
| | - Emmett T Cunningham
- d Department of Ophthalmology , California Pacific Medical Center , San Francisco , CA , USA.,e Department of Ophthalmology , Stanford University School of Medicine , Stanford , CA , USA.,f UCSF School of Medicine , The Francis I. Proctor Foundation , San Francisco , CA , USA
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Ozdemir R, Kucuk M, Dibeklioglu SE. Report of a Myocarditis Outbreak among Pediatric Patients: Human Herpesvirus 7 as a Causative Agent? J Trop Pediatr 2018; 64:468-471. [PMID: 29206935 DOI: 10.1093/tropej/fmx093] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND The etiology of myocarditis in children has not yet been completely elucidated. OBJECTIVE Medical records of eight pediatric patients diagnosed with acute myocarditis within a 41-day period in a small-town hospital were retrospectively analyzed. METHODS We examined antibody titers of adenovirus, Epstein-Barr virus, herpes simplex virus, respiratory syncytial virus, varicella-zoster virus and cytomegalovirus in peripheral blood. We used polymerase chain reaction (PCR) amplification to detect genetic sequences from Human herpesvirus (HHV) 7, HHV 6, enterovirus, measles or parvovirus in peripheral blood. RESULTS The causative agent was HHV 7 in four patients. HHV 7 sequences were detected through PCR in one patient with rapid deterioration. Of four patients with HHV 7, two presented with dilated cardiomyopathy. CONCLUSION To our knowledge, this is the first report to suggest HHV 7 as a causative agent for acute myocarditis. We believe HHV 7 should be considered as a possible etiologic pathogen for patients with suspected myocarditis.
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Affiliation(s)
- Rahmi Ozdemir
- Department of Pediatric Cardiology, Dumlupinar University Kutahya Evliya Celebi Training and Research Hospital, Kutahya 43040, Turkey
| | - Mehmet Kucuk
- Department of Pediatric Cardiology, Samsun Maternal and Child Hospital, Samsun 55070, Turkey
| | - Saime Ergen Dibeklioglu
- Department of Pediatrics, Dumlupinar University Kutahya Evliya Celebi Training and Research Hospital, Kutahya 43040, Turkey
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Rasa S, Nora-Krukle Z, Henning N, Eliassen E, Shikova E, Harrer T, Scheibenbogen C, Murovska M, Prusty BK. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med 2018; 16:268. [PMID: 30285773 PMCID: PMC6167797 DOI: 10.1186/s12967-018-1644-y] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 09/24/2018] [Indexed: 12/15/2022] Open
Abstract
Background and main text Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.
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Affiliation(s)
- Santa Rasa
- Institute of Microbiology and Virology, Rīga Stradiņš University, Riga, Latvia
| | - Zaiga Nora-Krukle
- Institute of Microbiology and Virology, Rīga Stradiņš University, Riga, Latvia
| | - Nina Henning
- Biocenter, Chair of Microbiology, University of Würzburg, Würzburg, Germany
| | - Eva Eliassen
- Biocenter, Chair of Microbiology, University of Würzburg, Würzburg, Germany
| | - Evelina Shikova
- Department of Virology, National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria
| | - Thomas Harrer
- Department of Internal Medicine 3, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Carmen Scheibenbogen
- Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Campus Virchow, Berlin, Germany
| | - Modra Murovska
- Institute of Microbiology and Virology, Rīga Stradiņš University, Riga, Latvia
| | - Bhupesh K Prusty
- Biocenter, Chair of Microbiology, University of Würzburg, Würzburg, Germany. .,Institute for Virology and Immunobiology, Würzburg, Germany.
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Rodriguez-Zuniga M, Torres N, Garcia-Perdomo H. Effectiveness of acyclovir in the treatment of pityriasis rosea. A systematic review and meta-analysis. An Bras Dermatol 2018; 93:686-695. [PMID: 30156618 PMCID: PMC6106661 DOI: 10.1590/abd1806-4841.20187252] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 09/20/2017] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND There is a lack of evidence to support acyclovir administration in pityriasis rosea. OBJECTIVE To determine the efficacy of acyclovir in patients with typical pityriasis rosea. METHODS A systematic review and meta-analysis of experimental studies was performed in MEDLINE, SCOPUS, EMBASE and others, from January 1990 to October 2016 on acyclovir for pityriasis rosea. Random effect model was used to find the pooled Risk Ratio. Outcomes, evaluated between weeks 1 to 8, were regression of lesions, cessation of lesions, decrease of symptoms and duration of disease. Comparisons were acyclovir vs. placebo; acyclovir vs. symptomatic treatment; acyclovir vs. antibiotic; acyclovir vs. observation and combined therapy (acyclovir plus symptomatic treatment) vs. symptomatic treatment alone. RESULTS Seven papers were analyzed with 324 participants, of which 159 received acyclovir and 165 were controls. Acyclovir was superior to placebo for complete regression of lesions at week 1 (Risk Ratio 5.72, CI95% 2.36-13.88). However, combined therapy was not superior to symptomatic treatment at week 4 (Risk Ratio 1.46, CI95% 0.93-2.29). Individual studies showed the superiority of acyclovir for the control of symptoms and pruritus. STUDY LIMITATIONS We faced differences designs of trials and inconsistency between reports. CONCLUSION Symptomatic treatment is a reasonable option for pityriasis rosea, and the addition of acyclovir is justified for the control of symptoms and pruritus.
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Affiliation(s)
- Milton Rodriguez-Zuniga
- Dermatology Department, Hospital Nacional Daniel Alcides Carrion,
Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Natalie Torres
- Dermatology Department, Hospital Nacional Dos de Mayo, Universidad
Nacional Mayor de San Marcos, Lima, Peru
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Abstract
Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropism in vivo and, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.
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Prusty BK, Gulve N, Rasa S, Murovska M, Hernandez PC, Ablashi DV. Possible chromosomal and germline integration of human herpesvirus 7. J Gen Virol 2017; 98:266-274. [PMID: 28284243 DOI: 10.1099/jgv.0.000692] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Human herpesvirus 7 (HHV-7) is a betaherpesvirus, and is phylogenetically related to both HHV-6A and HHV-6B. The presence of telomeric repeat sequences at both ends of its genome should make it equally likely to integrate into the human telomere as HHV-6. However, numerous studies have failed to detect germline integration of HHV-7, suggesting an important difference between the HHV-6A/-6B and HHV-7 genomes. In search of possible germline integrated HHV-7, we developed a sensitive and quantitative real-time PCR assay and discovered that primers designed against some parts of the HHV-7 genome can frequently miss HHV-7 positive clinical samples even though they work efficiently in cell-culture-derived HHV-7 positive materials. Using a primer pair against the U90 ORF of HHV-7, we identified a possible case of germline integration of HHV-7 with one copy of viral genome per cell in both peripheral blood cells and hair follicles. Chromosomal integration of HHV-7 in these individuals was confirmed by fluorescence in situ hybridization analysis. Germline integration of HHV-7 was further confirmed by detection of ~2.6 copies of HHV-7 in the hair follicles of one of the parents. Our results shed light on the complex nature of the HHV-7 genome in human-derived materials in comparison to cell-culture-derived materials and show the need for stringent criteria in the selection of primers for epidemiological HHV-7 studies.
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Affiliation(s)
- Bhupesh K Prusty
- Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany
| | - Nitish Gulve
- Department of Microbiology, Biocenter, University of Würzburg, 97074 Würzburg, Germany
| | - Santa Rasa
- August Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, 1069 Riga, Latvia
| | - Modra Murovska
- August Kirchenstein Institute of Microbiology and Virology, Riga Stradins University, 1069 Riga, Latvia
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Riva N, Franconi I, Meschiari M, Franceschini E, Puzzolante C, Cuomo G, Bianchi A, Cavalleri F, Genovese M, Mussini C. Acute human herpes virus 7 (HHV-7) encephalitis in an immunocompetent adult patient: a case report and review of literature. Infection 2017; 45:385-388. [PMID: 28386807 DOI: 10.1007/s15010-017-1014-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 03/30/2017] [Indexed: 12/01/2022]
Abstract
We report a case of an acute HHV-7 encephalitis involving the nucleus of the VI cranial nerve in an immunocompetent host. The patient was an adult male admitted to our Clinic with headache, diplopia, fever, nausea, vertigo, asthenia and general malaise. PCR for viral and bacterial genomes was run on both serum and cerebral spinal fluid (CSF) after performing lumbar puncture, resulting positive only for HHV-7 DNA on CSF. MRI showed hyperintensity in FLAIR signal in the dorsal pons, in the area of the VI cranial nerve nucleus. Empirical therapy with Acyclovir and Dexamethasone was started at the time of admission and was continued after the microbiology results. After three days of therapy diplopia, fever and other previous clinical manifestations improved and the patient recovered normal sight. Our case report contributes to a better understanding of the presentation, diagnosis and treatment of HHV-7 encephalitis in immunocompetent patients due to reactivation in adult age.
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Affiliation(s)
- Nicoletta Riva
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy.
| | - Iacopo Franconi
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
| | - Marianna Meschiari
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
| | - Erica Franceschini
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
| | - Cinzia Puzzolante
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
| | - Gianluca Cuomo
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
| | - Alessandro Bianchi
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
| | - Francesca Cavalleri
- Neuroradiology Unit, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino Estense di Modena, Azienda Unità Sanitaria Locale di Modena, Modena, Italy
| | - Maurilio Genovese
- Neuroradiology Unit, Department of Neuroscience, Nuovo Ospedale Civile S. Agostino Estense di Modena, Azienda Unità Sanitaria Locale di Modena, Modena, Italy
| | - Cristina Mussini
- Department of Infectious Diseases, University of Modena and Reggio Emilia, via largo del Pozzo 71, 41123, Modena, Italy
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Ongrádi J, Ablashi DV, Yoshikawa T, Stercz B, Ogata M. Roseolovirus-associated encephalitis in immunocompetent and immunocompromised individuals. J Neurovirol 2017; 23:1-19. [PMID: 27538995 PMCID: PMC5329081 DOI: 10.1007/s13365-016-0473-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 06/15/2016] [Accepted: 07/17/2016] [Indexed: 01/26/2023]
Abstract
The roseoloviruses, human herpesvirus (HHV)-6A, HHV-6B, and HHV-7, can cause severe encephalitis or encephalopathy. In immunocompetent children, primary HHV-6B infection is occasionally accompanied by diverse clinical forms of encephalitis. Roseolovirus coinfections with heterologous viruses and delayed primary HHV-7 infection in immunocompetent adults result in very severe neurological and generalized symptoms. Recovery from neurological sequelae is slow and sometimes incomplete. In immunocompromised patients with underlying hematological malignancies and transplantation, frequent single or simultaneous reactivation of roseoloviruses elicit severe, lethal organ dysfunctions, including damages in the limbic system, brain stem, and hippocampus. Most cases have been due to HHV-6B with HHV-6A accounting for 2-3%. The most severe manifestation of HHV-6B reactivation is post-transplantation limbic encephalitis. Seizures, cognitive problems, and abnormal EEG are common. Major risk factors for HHV-6B-associated encephalitis include unrelated cord blood cell transplantation and repeated hematopoietic stem cell transplantation. Rare genetic disorders, male gender, certain HLA constellation, and immune tolerance to replicating HHV-6 in persons carrying chromosomally integrated HHV-6 might also predispose an individual to roseolovirus-associated brain damage. At this time, little is known about the risk factors for HHV-7-associated encephalitis. Intrathecal glial cell destruction due to virus replication, overexpression of proinflammatory cytokines, and viral mimicry of chemokines all contribute to brain dysfunction. High virus load in the cerebrospinal fluid, hippocampal astrogliosis, and viral protein expression in HHV-6B-associated cases and multiple microscopic neuronal degeneration in HHV-7-associated cases are typical laboratory findings. Early empirical therapy with ganciclovir or foscarnet might save the life of a patient with roseolovirus-associated encephalitis.
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Affiliation(s)
- Joseph Ongrádi
- Institute of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
| | - Dharam V Ablashi
- HHV-6 Foundation, 1482 East Valley Road, Santa Barbara, CA, 93101, USA
| | - Tetsushi Yoshikawa
- Department of Pediatrics, Fujita Health University School of Medicine, 1-98, Kotsukake-cho, Dengakugakolo, Toyoake, Aichi, 470-1192, Japan
| | - Balázs Stercz
- Institute of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary
| | - Masao Ogata
- Department of Medical Oncology and Hematology, Oita University Hospital, Hasama-machi, Yufu City, 879-5593, Japan
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Mochizuki M, Sugita S, Kamoi K, Takase H. A new era of uveitis: impact of polymerase chain reaction in intraocular inflammatory diseases. Jpn J Ophthalmol 2016; 61:1-20. [PMID: 27787641 DOI: 10.1007/s10384-016-0474-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 07/28/2016] [Indexed: 12/17/2022]
Abstract
Uveitis is a sight-threatening intraocular inflammatory disorder which may occur from both infectious and non-infectious or autoimmune causes. The frequency of infectious uveitis and autoimmune uveitis varies depending on countries and regions. According to a nationwide survey conducted by the Japanese Ocular Inflammation Society, infectious and non-infectious uveitis accounted for 16.4 and 50.1% of new patients, respectively while the remaining 33.5% of new uveitis cases were not classified or were idiopathic uveitis. Infectious uveitis is particularly important because it causes tissue damage to the eye and may result in blindness unless treated. However, it can be treated if the pathogenic microorganisms are identified promptly and accurately. Remarkable advancements in molecular and immunological technologies have been made in the last decade, and the diagnosis of infectious uveitis has been greatly improved by the application of molecular and immunological investigations, particularly polymerase chain reaction (PCR). PCR performed on a small amount of ocular samples provides a prompt, sensitive, and specific molecular diagnosis of pathogenic microorganisms in the eye. This technology has opened a new era in the diagnosis and treatment of uveitis, enabling physicians to establish new clinical entities of uveitis caused by infectious microorganisms, identify pathogens in the eyes of many patients with uveitis, and determine prompt diagnosis and appropriate therapy. Here we review the PCR process, new PCR tests specialized for ocular diseases, microorganisms detected by the PCR tests, diseases in the eye caused by these microorganisms, and the clinical characteristics, diagnosis, and therapy of uveitis.
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Affiliation(s)
- Manabu Mochizuki
- Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. .,Miyata Eye Hospital, Miyakonojo, Miyazaki, Japan.
| | - Sunao Sugita
- Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan
| | - Koju Kamoi
- Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Hiroshi Takase
- Department of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
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Agut H, Bonnafous P, Gautheret-Dejean A. Update on infections with human herpesviruses 6A, 6B, and 7. Med Mal Infect 2016; 47:83-91. [PMID: 27773488 DOI: 10.1016/j.medmal.2016.09.004] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 09/19/2016] [Indexed: 11/19/2022]
Abstract
Human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7) are genetically related to cytomegalovirus. They belong to the Roseolovirus genus and to the Betaherpesvirinae subfamily. They infect T cells, monocytes-macrophages, epithelial cells, and central nervous system cells. These viruses are ubiquitous and are responsible for lifelong chronic infections, most often asymptomatic, in the vast majority of the general adult population. HHV-6B is responsible for exanthema subitum, which is a benign disease of infants. HHV-6A and HHV-6B also cause opportunistic infections in immunocompromised patients: encephalitis, hepatitis, bone marrow suppression, colitis, and pneumonitis. Their etiological role in chronic diseases such as multiple sclerosis, cardiomyopathy, and thyroiditis is still controversial. The pathogenicity of HHV-7 is less clear and seems to be much more restricted. Chromosomal integration of HHV-6A and HHV-6B is transmissible from parents to offspring and observed in about 1% of the general population. This integration raises the question of potential associated diseases and can be a confounding factor for the diagnosis of active infections by both viruses. The diagnosis of HHV-6A, HHV-6B, and HHV-7 infections is rather based on gene amplification (PCR), which allows for the detection and quantification of the viral genome, than on serology, which is mainly indicated in case of primary infection. Ganciclovir, foscarnet, and cidofovir inhibit the replication of HHV-6A, HHV-6B, and HHV-7. Severe infections may thus be treated but these therapeutic indications are still poorly defined.
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Affiliation(s)
- H Agut
- Service de virologie, CERVI, hôpitaux universitaires La Pitié Salpêtrière-Charles-Foix, Assistance publique-Hôpitaux de Paris, 83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Inserm, CIMI-Paris UMR 1135, Équipe 1 PVI, Sorbonne universités, UPMC université Paris 6, 75013 Paris, France.
| | - P Bonnafous
- Inserm, CIMI-Paris UMR 1135, Équipe 1 PVI, Sorbonne universités, UPMC université Paris 6, 75013 Paris, France.
| | - A Gautheret-Dejean
- Service de virologie, CERVI, hôpitaux universitaires La Pitié Salpêtrière-Charles-Foix, Assistance publique-Hôpitaux de Paris, 83, boulevard de l'Hôpital, 75651 Paris cedex 13, France; Inserm, CIMI-Paris UMR 1135, Équipe 1 PVI, Sorbonne universités, UPMC université Paris 6, 75013 Paris, France; Faculté de pharmacie, université Paris-Descartes, 75006 Paris, France.
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Miyazaki Y, Namba H, Torigoe S, Watanabe M, Yamashita N, Ogawa H, Morishima T, Yamada M. Monitoring of human herpesviruses-6 and -7 DNA in saliva samples during the acute and convalescent phases of exanthem subitum. J Med Virol 2016; 89:696-702. [PMID: 27648817 DOI: 10.1002/jmv.24690] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/17/2016] [Indexed: 02/06/2023]
Abstract
The amounts of the DNAs of human herpesviruses-6 (HHV-6) and -7 (HHV-7) in saliva samples were monitored during the acute and convalescent phases of exanthem subitum (ES) to elucidate the kinetics of virus shedding after ES. A total of 247 saliva samples were collected from 17 children (5 males and 12 females: 8-31 months old at onset). The monitoring period ranged from 152 to 721 days after onset, and in 15 children it was longer than 1 year. Among the 17 cases, 16 were attributed to HHV-6B, while a single case was attributed to HHV-7. Detection rates and average amounts of HHV-6 DNA in saliva samples after ES attributed to HHV-6B were low in the acute phase, increased to the maximum in the convalescent phase at 3-7 months, and then decreased. In addition, to investigate the source of infection, saliva samples from the older siblings (age 3-9 years) and parents of ES patients and children with a history of ES were also examined. The detection rate of HHV-6 DNA in saliva samples from 3- to 9-year-old children was significantly higher than the rate in adult saliva samples. Taken together, these findings suggest that the saliva of children in the convalescent phase of ES might be a more likely source of HHV-6 infection than that of adults. J. Med. Virol. 89:696-702, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Yuki Miyazaki
- Departments of Virology and Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Hikaru Namba
- Departments of Virology and Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | | | | | - Nobuko Yamashita
- Departments of Virology and Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.,Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Hirohito Ogawa
- Departments of Virology and Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Tsuneo Morishima
- Department of Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan.,Okayama Rosai Hospital, Okayama, Japan
| | - Masao Yamada
- Departments of Virology and Pediatrics, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan
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Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques. J Virol 2016; 90:6657-6674. [PMID: 27170755 PMCID: PMC4944276 DOI: 10.1128/jvi.00651-16] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 05/03/2016] [Indexed: 11/20/2022] Open
Abstract
Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. IMPORTANCE Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease.
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Takahashi K, Suzuki M, Iwata Y, Shigeta S, Yamanishi K, De Clercq E. Selective Activity of Various Nucleoside and Nucleotide Analogues against Human Herpesvirus 6 and 7. ACTA ACUST UNITED AC 2016. [DOI: 10.1177/095632029700800102] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We have developed a new sensitive enzyme immunoassay (EIA) and MTT (tetrazolium salt) assay for screening compounds against two variants of human herpesvirus 6 (HHV-6A, HHV-6B) and human herpesvirus 7 (HHV-7) and evaluated the anti-HHV-6 and HHV-7 activity of a series of anti-herpesvirus compounds and acyclic nucleoside phosphonate analogues. The results indicate that the pattern of activity of these compounds against these betaherpesviruses is similar to that for human cytomegalovirus (HCMV). The highest potency and selectivity against the two variants of HHV-6 and HHV-7 was demonstrated by S2242 (N7-isomer of 6-deoxy-ganciclovir). Also, ganciclovir (GCV), foscarnet, (phosphonoformic acid; PFA) and the acyclic nucleoside phosphonate analogues such as cidofovir (HPMPC) exhibited selective inhibitory activity against these viruses. Thymidine kinase (TK)-dependent drugs (acyclovir, ACV; brivudin, BVDU; and sorivudine, BVaraU) showed little, if any, activity. These results suggest a structural homology of the DNA polymerase and a lack of TK gene among these three betaherpesviruses (HHV-6, HHV-7 and HCMV). The finding that HHV-7 was highly sensitive to GCV also suggests that HHV-7 may have an HCMV-UL97-homologue gene for the phosphorylation of GCV. The present EIA method is more rapid and sensitive than the previously reported procedures and could be useful for the large-scale screening of compounds against HHV-6 and HHV-7.
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Affiliation(s)
- K Takahashi
- Department of Microbiology, Fukushima Medical College, 1 Hikarigaoka, Fukushima, 960-1 2, Japan
| | - M Suzuki
- Department of Microbiology, Fukushima Medical College, 1 Hikarigaoka, Fukushima, 960-1 2, Japan
| | - Y Iwata
- Department of Microbiology, Fukushima Medical College, 1 Hikarigaoka, Fukushima, 960-1 2, Japan
| | - S Shigeta
- Department of Microbiology, Fukushima Medical College, 1 Hikarigaoka, Fukushima, 960-1 2, Japan
| | - K Yamanishi
- Department of Microbiology, Osaka University School of Medicine, Osaka, Japan
| | - E De Clercq
- Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
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Abstract
Eight members of the human herpesvirus (HHV) family have been discovered to date. All the viruses have a characteristic virion structure and share a number of other features. From the perspective of potential treatments, these include the encoding of a protease enzyme which is essential for virus assembly, a DNA polymerase and at least one kinase enzyme which can phosphorylate nucleosides. The herpesviruses also demonstrate a number of mechanisms for avoiding the host immune system, including interference with different stages of the presentation of viral peptides on the cell surface by class I human leukcocyte antigen (HLA) proteins. Three members of the herpesvirus family (HHV-6, HHV-7 and HHV-8) have been discovered within the last 10 years. Both HHV-6 and HHV-7 cause exonthem subitum, although HHV-7 seems to be less pathogenic than HHV-6. HHV-6 also appears to be associated with a number of other disorders. HHV-8 was discovered by the newly developed technique of representational difference analysis, and was identified in Kaposi's sarcoma (KS) tissue. Although the studies to date do not prove that HHV-8 causes KS, they show that the virus is closely associated with the disease. Since discovery of these HHV has been facilitated by the development of new techniques, further technological advances could help to uncover new members of the family.
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Affiliation(s)
- P Griffiths
- Department of Virology, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK
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Munawwar A, Singh S. Human Herpesviruses as Copathogens of HIV Infection, Their Role in HIV Transmission, and Disease Progression. J Lab Physicians 2016; 8:5-18. [PMID: 27013807 PMCID: PMC4785766 DOI: 10.4103/0974-2727.176228] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Of eight human herpesviruses (HHVs), often, only herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. However, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the Acquired immunodeficiency syndrome (HIV/AIDS) has only very recently been recognized. Therefore, screening and treating subclinical HHV infections may offer slowing of HIV infection, disease progression, and its transmission. Beside HSV-1 and HSV-2, HHV-3 a causative agent of herpes zoster remained one of the first manifestations of HIV disease before the era of highly active antiretroviral therapy (HAART). HHV-5 also known as human Cytomegalovirus infection remains a significant risk factor for HIV-associated mortality and morbidity even in HAART era. It is proposed that Cytomegalovirus viremia could be a better predictor of HIV disease progression than CD4+ T-lymphocyte count. The role of HHV-4 or Epstein-Burr virus and HHV-6, HHV-7, and HHV-8 is still being investigated in HIV disease progression. This review provides insight into the current understanding about these 8 HHVs, their co-pathogenesis, and role in HIV/AIDS disease progression. The review also covers recent literature in favor and against administering anti-HHV treatment along with HAART for slower AIDS progression and interrupted sexual transmission.
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Affiliation(s)
- Arshi Munawwar
- Department of Laboratory Medicine, Division of Clinical Microbiology and Molecular Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Sarman Singh
- Department of Laboratory Medicine, Division of Clinical Microbiology and Molecular Medicine, All India Institute of Medical Sciences, New Delhi, India
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Agut H, Bonnafous P, Gautheret-Dejean A. Laboratory and clinical aspects of human herpesvirus 6 infections. Clin Microbiol Rev 2015; 28:313-35. [PMID: 25762531 PMCID: PMC4402955 DOI: 10.1128/cmr.00122-14] [Citation(s) in RCA: 193] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.
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Affiliation(s)
- Henri Agut
- Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France INSERM, CIMI-Paris U1135, PVI Team, Paris, France AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France
| | - Pascale Bonnafous
- Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France INSERM, CIMI-Paris U1135, PVI Team, Paris, France
| | - Agnès Gautheret-Dejean
- Sorbonne Universités, UPMC, CIMI-Paris UMRS CR7, PVI Team, Paris, France INSERM, CIMI-Paris U1135, PVI Team, Paris, France AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Service de Virologie, Paris, France Université René Descartes, Faculté de Pharmacie, Laboratoire de Microbiologie UPRES EA 4065, Paris, France
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47
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Virological and molecular biological evidence supporting herpes simplex virus type 1 corneal latency. Jpn J Ophthalmol 2015; 59:131-4. [DOI: 10.1007/s10384-014-0369-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 11/27/2014] [Indexed: 11/30/2022]
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Staheli JP, Dyen MR, Lewis P, Barcy S. Discovery and biological characterization of two novel pig-tailed macaque homologs of HHV-6 and HHV-7. Virology 2014; 471-473:126-40. [PMID: 25461538 PMCID: PMC4312206 DOI: 10.1016/j.virol.2014.10.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Revised: 08/13/2014] [Accepted: 10/02/2014] [Indexed: 11/28/2022]
Abstract
Human herpesvirus-6 (HHV-6) and -7 (HHV-7) are Roseoloviruses within the Betaherpesvirus family, which have a high prevalence and suspected involvement in a number of diseases. Using CODEHOP-based PCR, we identified homologs of both viruses in saliva of pig-tailed macaques, provisionally named MneHV-6 and MneHV-7. This finding supports the existence of two distinct Roseolovirus lineages before the divergence of humans and macaques. Using specific qPCR assays, high levels of MneHV-6 and MneHV-7 DNA were detected in macaque saliva, although the frequency was greater for MneHV-7. A blood screen of 283 macaques revealed 10% MneHV-6 DNA positivity and 25% MneHV-7 positivity, with higher prevalences of MneHV-6 in older females and of MneHV-7 in younger males. Levels of MneHV-6 were increased in animals coinfected with MneHV-7, and both viruses were frequently detected in salivary gland and stomach tissues. Our discovery provides a unique animal model to answer unresolved questions regarding Roseolovirus pathology.
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Affiliation(s)
- Jeannette P Staheli
- Center for Global Infectious Disease Research, Seattle Children׳s Research Institute, Seattle, Research Center, Seattle, WA, USA.
| | - Michael R Dyen
- Center for Global Infectious Disease Research, Seattle Children׳s Research Institute, Seattle, Research Center, Seattle, WA, USA.
| | - Patrick Lewis
- Center for Global Infectious Disease Research, Seattle Children׳s Research Institute, Seattle, Research Center, Seattle, WA, USA.
| | - Serge Barcy
- Center for Global Infectious Disease Research, Seattle Children׳s Research Institute, Seattle, Research Center, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
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Abstract
Roseola infantum, also known as exanthem subitum or sixth disease, is a generally benign febrile exanthem of infancy. It has a characteristic clinical course of high fever followed by the appearance of an exanthem upon defervescence. Febrile seizures are a frequent complication. Roseola is caused by infection with human herpesviruses 6 or 7 (HHV-6/7), which are acquired at a young age. Diagnosis is made by serology or by virus detection in body fluids and tissues. Treatment of roseola is supportive; recovery is usually complete with no significant sequelae. However, HHV-6/7 can reactivate in immunocompetent as well as immunocompromised individuals with severe systemic consequence.
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