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Medina JB, França Vieira E Silva F, Caixeta RAV, de Oliveira Rech B, Perez-Jardón A, Padín-Iruegas ME, Pérez-Sayáns M, Braz-Silva PH, Ortega KL. Torque teno virus as a marker of immune status in immunocompromised patients: A systematic review. Eur J Clin Invest 2025:e70068. [PMID: 40371633 DOI: 10.1111/eci.70068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Accepted: 04/28/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND Torque teno virus (TTV) is not known to cause disease in humans; however, chronic inflammatory conditions and immunosuppression states can favour TTV replication. This study aimed to verify the effectiveness of TTV as an immune biomarker. METHODS The protocol of this review was registered in PROSPERO (CRD42022331049) and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Thirty-three articles were selected and different groups of patients were assessed. In the solid organ and hematopoietic stem cell transplant groups, most studies reported that TTV viral load (VL) was highly detectable after transplantation and compared to controls, but the association with immune parameters showed conflicting results. In melanoma patients, no statistical difference in TTV VL was identified between susceptible and treatment-resistant patients. In lung cancer patients, viral load increases significantly with disease progression but decreases after chemotherapy. HIV-positive patients showed a higher VL than controls, but an inverse correlation with CD4+ was observed in half of the studies. Although 57.14% of all studies presented a low risk of bias, significant differences were observed between studies, particularly in the choice of the analyzed outcome, the parameter used to evaluate the patient's immune status, the presence of a control group, and the sample collection time points. CONCLUSIONS Although TTV seems to have the potential to be a promising biomarker of immunosuppression, further high-quality prospective clinical studies are still needed.
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Affiliation(s)
- Janaina B Medina
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - Fábio França Vieira E Silva
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
| | | | | | - Alba Perez-Jardón
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
| | - María Elena Padín-Iruegas
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
- Human Anatomy Area, University of Vigo, Vigo, Spain
| | - Mario Pérez-Sayáns
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
- ORALRES Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
| | - Paulo Henrique Braz-Silva
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
- Laboratory of Virology, Institute of Tropical Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Karem L Ortega
- Oral Medicine, Oral Surgery and Implantology Unit (MedOralRes), Faculty of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain
- Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
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Taheri M, Motamedifar M, Sarvari J, Yaghoobi R, Nikouyan N, Pirbonyeh N, Bagheri Lankarani K. Higher Frequency of Transfusion-Transmitted Virus (TTV) in HIV Patients in Comparison with Healthy Blood Donors. INTERNATIONAL JOURNAL OF HIGH RISK BEHAVIORS AND ADDICTION 2017; In Press. [DOI: 10.5812/ijhrba.59363] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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AbuOdeh R, Al-Mawlawi N, Al-Qahtani AA, Bohol MFF, Al-Ahdal MN, Hasan HA, AbuOdeh L, Nasrallah GK. Detection and genotyping of torque teno virus (TTV) in healthy blood donors and patients infected with HBV or HCV in Qatar. J Med Virol 2015; 87:1184-1191. [PMID: 25676255 DOI: 10.1002/jmv.24146] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/10/2014] [Indexed: 12/21/2022]
Abstract
Torque Teno virus (TTV) has been associated with non A-G hepatitis. The goal of this study was to estimate the infection rates and genotypic characteristics of TTV in the State of Qatar. A total of 644 blood samples representing different nationalities: (i) Qatari (118) and (ii) non-Qatari (526) nationals (mostly from Arab and South Eeast Asia countries) were tested for the presence of TTV DNA by nested PCR. The majority (573) of the blood samples belonged to healthy blood donors, whereas 54 and 53 of the blood samples belonged to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. The results obtained showed that the TTV infection rates in the healthy blood donors, and those infected with HBV or HCV patients were 81.4, 90.75 and 84.9%, respectively. Significant association between TTV viremia and age, or nationality was observed. Sequence analysis of PCR fragments amplified from the 5'-untranslated region (5'-UTR) of all (531) TTV positive samples showed that 65.5% (348/531) of the PCR fragment sequences were classified into main genogroup 3, followed by main genogroups 5 (24%), 2 (5.8%), and 1 (4.7%). Genogroup 4 was not detected among the our studied subjects. Phylogenetic and pairwise analyses using sequences from TTV viremic samples also showed an overall close similarity to the main genogroup 3. In conclusion, there was no significant difference in the rates of TTV detection among Qataris and non-Qataris and several genotypes, mainly genotype 3, were isolated.
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Affiliation(s)
- Raed AbuOdeh
- Department of Basic Sciences, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia
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Pirouzi A, Bahmani M, Feizabadi MM, Afkari R. Molecular characterization of Torque teno virus and SEN virus co-infection with HIV in patients from Southern Iran. Rev Soc Bras Med Trop 2014; 47:275-9. [PMID: 25075476 DOI: 10.1590/0037-8682-0073-2014] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2014] [Accepted: 06/23/2014] [Indexed: 01/03/2023] Open
Abstract
INTRODUCTION Torque teno virus (TTV) and SEN virus are circular single-stranded DNA viruses that cause blood-borne infections. The SEN virus (SEN-V) was originally detected in the serum of an injection drug user infected with human immunodeficiency virus (HIV). Recently TTV was discovered as a potential causative agent of non-A-E hepatitis. The aim of this study was to investigate the prevalence of the SEN-V-D/H and TTV in HIV patients and healthy blood donors in Iran. METHODS One hundred and fifty HIV patients with a mean age of 50.46 ± 18.46 years and 150 healthy blood donors with a mean age of 48.16 ± 13.73 years were included in this study. TTV and SEN-V were detected by the PCR and were quantitatively assayed by competitive PCR (nested and semi-nested PCR). Restriction fragment length polymorphisms (RFLPs) were used to determine the heterogeneity of TTV. RESULTS TTV and SEN-V were detected 96 (64%) and 84 (56%) of 150 HIV patients respectively. These rates were 34% (n=51) and 37.33% (n=56) in healthy blood donors (significant, p<0.05). PCR detected SEN-V/TTV DNA from 32 of the healthy blood donors (21.33%), while 65 (43.33%) of HIV patients were positive for SEN-V/TTV DNA. Of 150 HIV patients, 32.66% and 23.33% were positive for SEN-V-H and SEN-V-D, respectively and 18.66% (n=28) were co-infected with SEN-V-D/H. CONCLUSIONS The prevalence of SEN-VD/H and TTV is higher in HIV patients than in healthy blood donors in Southern Iran. Our results suggest that TTV and SEN-V might play a role in the development of liver disease in patients with immunodeficiency diseases.
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Affiliation(s)
- Aliyar Pirouzi
- Cellular and Molecular Gerash Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mirzakhalil Bahmani
- Cellular and Molecular Gerash Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Mehdi Feizabadi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Rouhi Afkari
- Cellular and Molecular Gerash Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Irshad M, Mandal K, Singh S, Agarwal SK. Torque teno virus infection in hemodialysis patients in North India. Int Urol Nephrol 2010; 42:1077-1083. [PMID: 19777363 DOI: 10.1007/s11255-009-9648-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2009] [Accepted: 09/09/2009] [Indexed: 12/31/2022]
Abstract
This study describes the prevalence and association of Torque teno virus (TTV) infection with blood-transmitted viral hepatitis including hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with chronic renal failure (CRF) on maintenance hemodialysis (HD). TTV infection was diagnosed by detection of TTV-DNA in serum, using the polymerase chain reaction (PCR) technique. TTV-DNA was estimated in a total number of one hundred patients with CRF and in 100 voluntary blood donors as controls. The markers of HBV and HCV were also tested in sera samples of these patients. TTV-DNA was detected in 39 of 100 patients (39%) with CRF and in 27 of 100 (27%) healthy controls. The analysis of the results demonstrated HBsAg, IgM anti-HBc, anti-HCV, and HCV core antigen in 5.0, 3.0, 6.0, and 4.0% of patients, respectively. This study could not show any association of TTV with HBV and HCV infections for the transmission pattern or any impact on severity of diseases caused by these viruses in CRF patients. TTV also could not show any association with demographic characteristics of patients, duration of dialysis, number of blood transfusions and renal/liver function of the patients. As such, this study concludes that TTV appears as a benign pathogen, showing no sign of renal/liver damage or any change in the severity of diseases caused by blood-borne hepatitis viruses.
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Affiliation(s)
- Mohammad Irshad
- Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.
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Vasilyev EV, Trofimov DY, Tonevitsky AG, Ilinsky VV, Korostin DO, Rebrikov DV. Torque Teno Virus (TTV) distribution in healthy Russian population. Virol J 2009; 6:134. [PMID: 19735552 PMCID: PMC2745379 DOI: 10.1186/1743-422x-6-134] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2009] [Accepted: 09/07/2009] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Torque teno virus (TTV) is a circular, single-stranded DNA virus that chronically infects healthy individuals of all ages worldwide. There is a lot of data on the prevalence and genetic heterogeneity of TTV in healthy populations and in patients with various diseases now available. However, little is known about TTV load among healthy human population. In this study we analyzed TTV load in the group of 512 Russian elite athletes, who are supposed to be, by some standards, the healthiest part of the human population. RESULTS The prevalence rate of TTV among the Russian Olympic Reserve members was 94% (for test sensitivity about 1000 genome equivalents per 1 ml of blood). Quantities varied from 103 (which corresponded to detection limit) to 1010 copies per 1 ml of blood, with median at 2.7 x 106 copies. CONCLUSION About 94% of healthy individuals in Russian population have more than 1000 TTV genome copies per 1 ml of blood. This result exceeds the previously published data, and can be explained by either more sensitive PCR test system or by higher TTV distribution in Russian population or both. TTV viral load neither depends on gender, nor age.
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Affiliation(s)
- Evgeny V Vasilyev
- DNA-Technology JSC, Kashirskoe shosse, 23-5-16, Moscow, 115478, Russia.
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Saláková M, Nemecek V, Tachezy R. TTV and HPV co-infection in cervical smears of patients with cervical lesions. BMC Infect Dis 2009; 9:118. [PMID: 19638204 PMCID: PMC2736169 DOI: 10.1186/1471-2334-9-118] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2009] [Accepted: 07/28/2009] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The female lower genital tract is a gateway for pathogens entering the host through the mucous membrane. One of the prevalent human viruses is Torque teno virus (TTV). The major reported routes of TTV transmission are fecal-oral and parenteral. Furthermore, other modes of transmission, e.g. sexual contact, are suggested. To investigate the sexual route of TTV transmission, cervical smears of healthy women and those with cervical lesions were screened for the presence of TTV DNA. METHODS TTV DNA was studied in cervical smears of 95 patients with cervical lesions and 55 healthy women. Paired serum samples were available from 55 and 42 women, respectively. All healthy women had normal cytology while 44 patients had histologically confirmed low-grade lesion (LGL) and 51 high-grade lesion (HGL). TTV DNA was detected with primers specific for the non-coding region. In 40 paired cervical smears and serum samples, the phylogenetic group of TTV isolates was determined. The presence of HPV DNA in cervical smears was detected by means of PCR with MY09/11 primers. RESULTS The prevalence of TTV DNA in cervical smears of healthy women was 52.7% and was comparable with that in paired serum samples (50%). Symptomatic women had significantly higher prevalence of TTV DNA in cervical smears (74.7%) than healthy controls. The TTV DNA prevalence in patient serum samples was 51%. The phylogenetic groups of TTV serum isolates were concordant with those of TTV from cervical smears of the same subjects. In cervical smears, a wider variety of TTV isolates was found. The viral loads in cervical smears were 10 to 1000 times as high as in sera. The HPV-positive study subjects had significantly higher TTV DNA prevalence than HPV negatives. The prevalence of TTV was not associated with disease severity. CONCLUSION High prevalence of TTV in cervical smears suggests that sexual transmission is another mode of expansion of TTV infection among the population. The higher viral load in cervical smears than in the respective serum samples might indicate active TTV replication in the female genital tract. Nevertheless, cooperation between TTV and HPV needs to be further investigated.
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Affiliation(s)
- Martina Saláková
- Department of Experimental Virology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
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Irshad M, Joshi YK, Sharma Y, Dhar I. Transfusion transmitted virus: A review on its molecular characteristics and role in medicine. World J Gastroenterol 2006; 12:5122-5134. [PMID: 16937521 PMCID: PMC4088008 DOI: 10.3748/wjg.v12.i32.5122] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2006] [Revised: 05/15/2006] [Accepted: 05/22/2006] [Indexed: 02/06/2023] Open
Abstract
The present review gives an updated overview of transfusion transmitted virus (TTV), a novel agent, in relation to its molecular characteristics, epidemiological features, modes of transmission, tissue tropism, pathogenesis, role in various diseases and its eradication from the body. TTV, a DNA virus, is a single stranded, non-enveloped, 3.8 kb long DNA virus with a small and covalently closed circular genome comprising 3852 bases. It was tentatively designated Circinoviridae virus. TTV genome sequence is heterogeneous and reveals the existence of six different genotypes and several subtypes. TTV has been reported to transmit not only via parenteral routes, but also via alternate routes. This virus has been detected in different non-human primates as well. At present, TTV is detected by polymerase chain reaction (PCR) with no other available diagnostic assays. It shows its presence globally and was detected in high percent populations of healthy persons as well as in various disease groups. Initially it was supposed to have strong association with liver disease; however, there is little evidence to show its liver tropism and contribution in causing liver diseases. It shows high prevalence in hemodialysis patients, pointing towards its significance in renal diseases. In addition, TTV is associated with several infectious and non-infectious diseases. Though, its exact pathogenesis is not yet clear, TTV virus possibly resides and multiplies in bone marrow cells and peripheral blood mononuclear cells (PBMCs). Recently, attempts have been made to eradicate this virus with interferon treatment. More information is still needed to extricate various mysteries related to TTV.
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Affiliation(s)
- M Irshad
- Clinical Biochemistry Division, Department of Laboratory Medicine, PO Box -4938, A I I M S, New Delhi-110029, India.
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Desai MM, Pal RB, Banker DD. Molecular epidemiology and clinical implications of TT virus (TTV) infection in Indian subjects. J Clin Gastroenterol 2005; 39:422-9. [PMID: 15815211 DOI: 10.1097/01.mcg.0000159219.93160.bc] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
GOALS This study was aimed at obtaining data on the epidemiology and clinical course of TT virus (TTV) infections among Indian subjects. BACKGROUND The TTV is a nonenveloped DNA virus, first identified in the peripheral blood of individuals with posttransfusion hepatitis of unknown etiology. There has been much conjecture regarding the disease association of this virus. STUDY A total of 494 serum specimens from various groups of high-risk and control subjects were screened for TTV DNA by a semi-nested PCR, using the ORF1-derived N22 primers. The sera were also screened for the HBsAg surface antigen by an ELISA, HCV RNA by a 5' NCR-based RT-PCR and GBV-C/HGV RNA by a 5' UTR-based RT-PCR. The clinical and hepatic profiles of the various subjects were also studied. Seventy-one randomly picked TTV isolates were directly sequenced and their phylogeny was studied. RESULTS TTV showed an overall positivity rate of 45.34% with a significant higher prevalence of 52.9% among the high-risk subjects as against a prevalence of 28% among healthy control subjects (P < 0.001). Abnormal liver function profiles were frequent among TTV viremic individuals and among the acute hepatitis cases studied a higher mortality rate correlated with a superimposed TTV infection. The 71 TTV isolates sequenced were found to belong to genotype 1a being closely homologous to TTV prototype TA278. CONCLUSION The TT virus shows a significant prevalence in the Indian population, particularly among subjects at risk for acquiring parenterally transmitted infections. Our study corroborates a putative role of the virus in the etiology of liver disease, particularly in coinfection with other agents.
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Affiliation(s)
- Mayura M Desai
- Department of Microbiology, Sir Hurkisondas Nurrotumdas Medical Research Society, Sir H. N. Hospital and Research Centre, Mumbai, India
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Saláková M, Němeček V, König J, Tachezy R. Age-specific prevalence, transmission and phylogeny of TT virus in the Czech Republic. BMC Infect Dis 2004; 4:56. [PMID: 15575965 PMCID: PMC539280 DOI: 10.1186/1471-2334-4-56] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2004] [Accepted: 12/03/2004] [Indexed: 11/18/2022] Open
Abstract
Background TT virus is prevalent worldwide, but its prevalence and genotype distribution in Central and East-Europe has not been determined. The high prevalence of TTV in multiply-transfused patients points to the importance of a parenteral mode of transmission, but since more than half of the general population is infected other possible routes of transmission must be considered. Methods In our study, we investigated the epidemiology, transmission and phylogeny of TTV in the Czech Republic. The following groups were selected: a control group of 196 blood donors, 20 patients with hemophilia, 49 intravenous drug users, 100 sex workers, 50 penitentiary prisoners, 208 healthy children aged 1 to 14 years, 54 cord blood samples, 52 patients with non-A-E hepatitis, 74 patients with hepatitis C, and 51 blood donors with increased ALT levels. Primers specific for the non-coding region were used. The genotype distribution was studied in 70 TTV-positive samples. Results The prevalence rate of TTV among the Czech population was 52.6%. We have shown that TTV is not transmitted prenatally. Children were infected after birth with two peaks: one at the age of two years and the other after the beginning of primary school. Adults have shown a further increase in the TTV prevalence with age. The highest TTV prevalence was found in the group of patients who had received multiple blood transfusions. The TTV prevalence rate in subjects at an increased risk of sexual transmission was not significantly higher than in the general population. Genotypes G2 and G1 were most prevalent among the Czech population, followed by G8 and G3. The subjects positive for markers of HBV and/or HCV infection tested significantly more often TTV DNA positive, which is suggestive of a common route of transmission of these three infections. Conclusions This study on TTV prevalence, mode of transmission and age-specific prevalence is the most extensive study performed in Central and Eastern Europe. It showed insights into the epidemiology of TTV infection, but failed to associate TTV infection with clinical manifestations.
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Affiliation(s)
- Martina Saláková
- Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic
| | - Vratislav Němeček
- National Reference Laboratory for Hepatitis, National Institute of Health, Prague, Czech Republic
| | - Jaroslav König
- National Reference Laboratory for Hepatitis, National Institute of Health, Prague, Czech Republic
| | - Ruth Tachezy
- Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic
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Al-Moslih MI, Abuodeh RO, Hu YW. Detection and genotyping of TT virus in healthy and subjects with HBV or HCV in different populations in the United Arab Emirates. J Med Virol 2004; 72:502-8. [PMID: 14748076 DOI: 10.1002/jmv.20017] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
TT virus (TTV) and TTV-like viruses (TTVLs) have been reported to be associated with non-A-E hepatitis. To determine the rate of infection and genotypic characteristics of TTV in the United Arab Emirates (UAE), a total of 449 serum samples representing different populations in the UAE and comprising healthy as well as patients positive for HBsAg and HCV were screened. National subjects (n = 200) and non-nationals residing in the UAE (n = 249) were tested by PCR. The results obtained showed that the rate of TTV infection in healthy nationals, and those with HBsAg or antibody to HCV were 34.9, 97.9, and 95.7, respectively, compared to 89.1% (115/129), 89.2% (66/74), and 84.8% (39/46), respectively, in non-nationals. Sequence analysis of the untranslated region (UTR) using 71 clones generated from the PCR products of eight serum samples from healthy individuals (four nationals and four non-nationals) showed that 83.1% of the TTV clones were classified into groups 1-4, whereas 16.9% into possibly new genotype(s). The analysis also revealed that healthy national subjects carried multiple viruses. Phylogenetic analysis of representative sequences revealed clustering of clones into at least five major groups. Also, when compared to reference genotypes (from GenBank), two of our clones belonged to two previously identified genotypes. Non-significant gender differences were seen in all ethnic groups studied (P > 0.05). In conclusion, the rate of TTV infection in the UAE nationals is significantly lower (P < 0.05) than that of the non-nationals and several genotypes were isolated with common multi-infections.
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Affiliation(s)
- Moslih I Al-Moslih
- College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
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Gallian P, Biagini P, Attoui H, Cantaloube JF, Dussol B, Berland Y, de Micco P, de Lamballerie X. High genetic diversity revealed by the study of TLMV infection in French hemodialysis patients. J Med Virol 2002; 67:630-5. [PMID: 12116016 DOI: 10.1002/jmv.10150] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
TT virus-like minivirus (TLMV) was recently discovered as a human circovirus. Little is known about its natural history and molecular epidemiology. A study of TLMV infection is described in a population of French hemodialysis patients. TLMV DNA was tested by seminested PCR system located in the noncoding region in 81 patients divided into seven groups according to the origin of their renal disease. Quantitation of TLMV DNA in serum was carried out. Sequences from 28 patients were compared with 40 sequences retrieved from databases and 53 TLMV sequences cloned from the serum of a single patient. The prevalence of TLMV DNA in hemodialysis patients was 95.1%. In this study, 24 samples (29.6%) presented viral loads of > 125 equivalents of plasmid (Ep)/ml, and only 6 (7.8%) had viral loads of > 125 x 10(2) Ep/ml. A significant correlation (P < 0.029) was found between viral loads of > 125 x 10(2) Ep/ml and the neoplastic origin of end-stage renal disease. Analysis of 53 sequences cloned from a single individual demonstrated high sequence variability, as shown by the genetic distance of 40.2%. This genetic distance is comparable to that between the most divergent sequences of TLMV reported to date (43.5%). These data suggest that TLMV viral load is possibly related to the level of immunocompetence of hemodialysis patients; the genetic diversity of TLMV is extremely high; and co-infection by different strains is possible.
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Affiliation(s)
- Pierre Gallian
- Unité des Virus Emergents, Université de la Méditerranée, Marseille, France
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Lai YC, Hu RT, Yang SS, Wu CH. Coinfection of TT virus and response to interferon therapy in patients with chronic hepatitis B or C. World J Gastroenterol 2002; 8:567-70. [PMID: 12046094 PMCID: PMC4656445 DOI: 10.3748/wjg.v8.i3.567] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2002] [Revised: 04/23/2002] [Accepted: 05/25/2001] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the serum positive percentage of TT virus (TTV) in patients with chronic hepatitis B or C and the response of the coinfected TTV to interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS We retrospectively studied the serum samples of 70 patients with chronic hepatitis who had received IFN-alpha therapy from January 1997 to June 2000, which included 40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up for at least 6 months after the end of IFN therapy. The serum TTV DNA was detected using the polymerase chain reaction (PCR) before and every month during the course of IFN treatment. RESULTS TTV infection was detected in 15% (6/40) of the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group. Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6 of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was found all during the first month of IFN therapy in the 9 patients. There was no correlation between the seroconversion of TTV and the biochemical changes of the patients. CONCLUSION TTV is not infrequently coinfected in patients with chronic hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN-sensitive. However, the loss of serum TTV DNA does not affect the clinical course of the patients with chronic hepatitis B or C.
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Affiliation(s)
- Yung-Chih Lai
- Liver Unit, Department of Internal Medicine, Cathay General Hospital, 280 Jen-Ai Rd., Sec. 4,Taipei, Taiwan 106.
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Yazici M, Cömert MR, Mas R, Guney C, Cinar E, Kocar IH. Transfusion-transmitted virus prevalence in subjects at high risk of sexually transmitted infection in Turkey. Clin Microbiol Infect 2002; 8:363-7. [PMID: 12084105 DOI: 10.1046/j.1469-0691.2002.00423.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To assess the possible sexual transmission of virus and to identify the prevalence of TTV viremia in Turkey and its association with other hepatotropic viruses. METHODS Serum samples were collected from 81 subjects (74 prostitutes and seven homosexual men) at high risk of sexually transmitted infection and from 81 healthy controls (74 females and seven males). Sera of patients and controls were tested for TTV, hepatitis A virus, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Also, serum alanine and aspartate aminotransferases were measured. RESULTS The prevalence rates of TTV viremia in the risk group and control group were 86.4% and 82.7%, respectively. There was a statistical difference in mean age between TTV-infected and uninfected subjects (38.6 +/- 9.9 versus 32.2 +/- 6.1 years, respectively, P < 0.001). Prevalence rates of TTV infection in subjects with positive anti-HAV and positive anti-HBc were high when compared with subjects who were negative for these. CONCLUSION We suggest that TTV infection has a diverse route of transmission, and its prevalence increases with age; also, the prevalence rate of TTV is high in certain risk groups. The prevalence rates of TTV in the group at risk for sexual transmission (86.4%) and in the control group (82.7%) were among the highest ever reported in the world. Also, we suggest that TTV generally does not cause clinical disease, in spite of this high prevalence.
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Affiliation(s)
- M Yazici
- Department of Internal Medicine, Gülhane School of Medicine, Ankara, Turkey
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15
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Krekulova L, Rehak V, Killoran P, Madrigal N, Riley LW. Genotypic distribution of TT virus (TTV) in a Czech population: evidence for sexual transmission of the virus. J Clin Virol 2001; 23:31-41. [PMID: 11595582 DOI: 10.1016/s1386-6532(01)00185-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND TTV is a new DNA virus distinguished by its high degree of strain heterogeneity. The geographic clustering of viral genotypes suggests frequent community transmission. While no specific human disease has yet been linked to it, a transmission mechanism that facilitates strain diversity may eventually select for a strain that will become pathogenic. OBJECTIVE This study was performed to examine the prevalence, genotypic distribution, and mode of transmission of TTV in detail. STUDY DESIGN Three groups of study subjects were recruited between October 1998 and January 2000 in Prague, Czech Republic. Group 1 included 152 injection drug users with liver disease; group 2 included 102 persons with liver disease who denied ever using injection drugs; group 3 included 111 prospective blood donors. TTV DNA was detected from blood by a semi-nested PCR assay, and a selected set of PCR products was genotyped by direct sequencing. Factors associated with TTV prevalence in groups 1 and 2 subjects were compared. RESULTS TTV was detected in 15.8, 13.7, and 13.5% of Groups 1, 2, and 3 subjects, respectively (P>0.05). The most common genotype was 2 (54%), followed by 1 (13%). The prevalence of TTV viremia was nearly three times higher in persons with a present or past history of hepatitis B compared to those without (P<0.05). TTV prevalence increased proportionately with the number of lifetime sex partners in both groups (P<0.05); it was highest (32%) among non-users of injection drugs who had five or more lifetime sex partners. CONCLUSION TTV prevalence in the Czech population is similar among blood donors, persons with liver disease, as well as in a high-risk population of injection drug users. TTV appears to be sexually transmitted.
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Affiliation(s)
- L Krekulova
- Division of Infectious Diseases, School of Public Health, University of California, Berkeley, 140 Warren Hall, Berkeley, CA 94720, USA
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16
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Masia G, Ingianni A, Demelia L, Faa G, Manconi PE, Pilleri G, Ciancio A, Rizzetto M, Coppola RC. TT virus infection in Italy: prevalence and genotypes in healthy subjects, viral liver diseases and asymptomatic infections by parenterally transmitted viruses. J Viral Hepat 2001; 8:384-90. [PMID: 11555197 DOI: 10.1046/j.1365-2893.2001.00287.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
This study was aimed to evaluate TT virus prevalence in subjects with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in patients affected by hepatitis of unknown origin (non-A-non-E hepatitis) and in healthy subjects who had not been exposed to HBV, HCV and HIV. A total of 317 subjects were tested; 40 were HBsAg asymptomatic carriers, 57 subjects were anti-HCV positive (45 without chronic hepatitis and 12 with HCV-related chronic hepatitis), and 27 had chronic non-A-non-E hepatitis. Fifty-seven subjects were intravenous drug users (IVDUs) (52 with HCV or/and HIV infections), seven patients underwent a liver transplant for fulminant hepatitis and 137 were healthy subjects from the general population. Overall, TTV-DNA was detected in 62 subjects (19.6%): in 17.9% of the HBsAg carriers, in 14% of the anti-HCV-positive patients (in 8.3% and in 15.5% of patients with and without chronic hepatitis, respectively), in 22.2% of non-A-non-E hepatitis patients, in 22.8% of IVDUs, in 57.1% of fulminant hepatitis patients. TTV-DNA was also found in 20.4% healthy subjects. The prevalence in the different subgroups was not statistically different. The genotypes were identified in 40 of the 62 (64.5%) TTV-DNA positive samples: genotype 1a in 17.5%, 1b in 27.5%, genotype 2 in 27.5%, genotype 3 in 15.0%, genotype 4 in 5.0% and genotype 5 in 7.5%; the genotype distribution in the subsets of patients was not significantly different. In conclusion, this study showed that TTV infection is common in Italy; it is widespread throughout the entire population and five genotypes are present in Sardinia. Our results further dismiss the role of TTV as cofactor in influencing the clinical course of infections with other hepatitis viruses as well as the role of HIV in enhancing TTV transmission and replication.
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Affiliation(s)
- G Masia
- Department of Public Health, University of Cagliari, Cagliari, Italy
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17
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Biagini P, Gallian P, Attoui H, Cantaloube JF, Touinssi M, de Micco P, de Lamballerie X. Comparison of systems performance for TT virus detection using PCR primer sets located in non-coding and coding regions of the viral genome. J Clin Virol 2001; 22:91-9. [PMID: 11418356 DOI: 10.1016/s1386-6532(01)00179-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
BACKGROUND the heterogeneity of the TT virus (TTV) DNA prevalence values reported from comparable human cohorts suggests that diagnostic PCR protocols still require to be optimized. OBJECTIVES to design TTV PCR primer sets with low genotype restriction and to compare their performances with commonly used amplification systems. STUDY DESIGN we compared full length TTV genomic sequences and identified conserved nucleotide patterns in the 5' and 3' non-coding regions of the viral genome. This permitted to design two new primer sets usable for the PCR amplification of the most divergent human isolates of TTV described to date. The performances of these amplification systems were compared with those of three other PCR systems earlier used for prevalence studies. RESULTS the primer systems P5Bx and P3Bx exhibited higher PCR scores than the other systems tested; 14 to 34% improvement values were obtained, and divergent positive results of earlier described PCR systems were confirmed systematically by our new detection assays. CONCLUSIONS an optimized detection of TT virus DNA is a pre-requisite for the accurate epidemiological survey of viral infection and for the realization of phylogenetic studies. Such PCR systems with low genotype restriction will be helpful in the future for a better knowledge of natural history of TT virus infection.
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Affiliation(s)
- P Biagini
- Unité des Virus Emergents, Laboratoire de Virologie Moléculaire, Etablissement Français du Sang Alpes-Méditerranée, 149, Bd Baille, 13005, Marseille, France
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18
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Rezza G, Zaccarelli M, Giuliani M, Calcaterra S, Garbuglia AR, Catalani C, Benvenuti M, Di Carlo A, Ippolito G, Antinori A. Sexual Transmission of Transfusion-Transmitted Virus. Sex Transm Dis 2001; 28:298-9. [PMID: 11354270 DOI: 10.1097/00007435-200105000-00012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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19
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Touinssi M, Gallian P, Biagini P, Attoui H, Vialettes B, Berland Y, Tamalet C, Dhiver C, Ravaux I, De Micco P, De Lamballerie X. TT virus infection: prevalence of elevated viraemia and arguments for the immune control of viral load. J Clin Virol 2001; 21:135-41. [PMID: 11378494 DOI: 10.1016/s1386-6532(01)00157-3] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The most recent polymerase chain reaction (PCR) detection protocols for the TT virus (TTV) permit one to identify the presence of viral DNA in the serum of a majority of healthy individuals, in the absence of any particular risk factor. This is in contrast with previous epidemiological studies that reported a higher prevalence of TTV infection in populations such as haemodialysis patients (HD), haemophiliacs, intravenous drug users or diabetics. OBJECTIVES To show that these discrepant results were due to the different sensitivity (number of viral copies detected) of the detection protocols used in initial and more recent epidemiological studies. STUDY DESIGN AND RESULTS We designed a standardised primary PCR assay that detects only viraemia >5x10(3) to 5x10(4) copies/ml for genotypes 1, 2 and 3, and compared the results of this test with those of a nested PCR assay which is 100-fold more sensitive. Viraemia >5x10(3) to 5x10(4) copies/ml were statistically more frequent in HD patients (54.3%), diabetics (54.7%), and HIV-infected patients with CD4 cells <200/mm(3) (69%) than in blood donors (37%) or HIV-infected patients with CD4 cells >500/mm(3) (33%). CONCLUSIONS These data suggest a possible relationship between the prevalence of elevated viral loads and the level of immunocompetence of the populations studied, and therefore that of an immune control of TTV viraemia. This corroborates previous findings showing that the stimulation of the immune system by an interferon treatment was able to clear TTV viraemia.
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Affiliation(s)
- M Touinssi
- Unité des Virus Emergents, Laboratoire de Virologie Moléculaire, Tropicale et Transfusionnelle, Faculté de Médecine de Marseille, Boulevard Jean Moulin, 13385 Marseille cedex 05, France
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20
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Bendinelli M, Pistello M, Maggi F, Fornai C, Freer G, Vatteroni ML. Molecular properties, biology, and clinical implications of TT virus, a recently identified widespread infectious agent of humans. Clin Microbiol Rev 2001; 14:98-113. [PMID: 11148004 PMCID: PMC88963 DOI: 10.1128/cmr.14.1.98-113.2001] [Citation(s) in RCA: 164] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
TT virus (TTV) was first described in 1997 by representational difference analysis of sera from non-A to non-G posttransfusion hepatitis patients and hence intensively investigated as a possible addition to the list of hepatitis-inducing viruses. The TTV genome is a covalently closed single-stranded DNA of approximately 3.8 kb with a number of characteristics typical of animal circoviruses, especially the chicken anemia virus. TTV is genetically highly heterogeneous, which has led investigators to group isolates into numerous genotypes and subtypes and has limited the sensitivity of many PCR assays used for virus detection. The most remarkable feature of TTV is the extraordinarily high prevalence of chronic viremia in apparently healthy people, up to nearly 100% in some countries. The original hypothesis that it might be an important cause of cryptogenic hepatitis has not been borne out, although the possibility that it may produce liver damage under specific circumstances has not been excluded. The virus has not yet been etiologically linked to any other human disease. Thus, TTV should be considered an orphan virus.
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Affiliation(s)
- M Bendinelli
- Virology Section, Department of Biomedicine and Retrovirus Center, University of Pisa, Pisa, Italy.
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21
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Shibata M, Morizane T, Baba T, Inoue K, Sekiyama K, Yoshiba M, Mitamura K. TT virus infection in patients with fulminant hepatic failure. Am J Gastroenterol 2000; 95:3602-6. [PMID: 11151899 DOI: 10.1111/j.1572-0241.2000.03301.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE A new DNA virus, which has been designated the TT virus, was discovered in 1997. It is not clear whether TT virus is a cause of any of the types of hepatitis. We conducted a case-control study to test the hypothesis that the presence of TT virus is a necessary condition for the development of fulminant hepatic failure in people who have non-A, -B, or -C hepatitis. METHODS We studied 55 patients with fulminant hepatic failure [28 men, 27 women, mean (+/- SD) age, 47 +/- 15 yr], 32 patients with acute hepatitis (18 men, 14 women, mean age, 38 +/- 15 yr), and 200 healthy subjects (106 men, 94 women, mean age, 42 +/- 14 yr). TT virus DNA was detected in sera by a nested polymerase chain reaction using a primer set for genotype 1. RESULTS TT virus was more frequently detected in patients with fulminant hepatic failure [in 33 of 55 (60%); 95% confidence interval (CI), 47-73%] than in those with acute hepatitis [in 8 of 32 (25%); 95% CI, 10-40%; p = 0.0016] or in healthy subjects [in 50 of 200 (25%); 95% CI, 19-31%; p < 0.0001]. TT virus was detected at a significantly higher rate in non-A, -B, or -C fulminant hepatic failure [in 18 of 22 (82%); 95% CI, 66-98%] than in fulminant hepatic failure of A, B, or C type [45%, 28-62%, 15/33; p = 0.007] or in non-A, -B, or -C acute hepatitis [24%, 3-44%, 4/17; p = 0.0003]. The logistic regression analysis selected TT virus (p = 0.0009), age (p = 0.0116), and etiology (p = 0.0309) as independent variables associated with fulminant hepatic failure (coefficient of determination, 0.2335). CONCLUSIONS TT virus comparatively plays a role in the pathogenesis of non-A, -B, or -C fulminant hepatic failure.
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Affiliation(s)
- M Shibata
- Second Department of Internal Medicine, Showa University, School of Medicine, Tokyo, Japan
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22
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Lin CL, Kyono W, Tongson J, Chua PK, Easa D, Yanagihara R, Nerurkar VR. Fecal excretion of a novel human circovirus, TT virus, in healthy children. CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY 2000; 7:960-3. [PMID: 11063506 PMCID: PMC95993 DOI: 10.1128/cdli.7.6.960-963.2000] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The role of TT virus (TTV) as a human pathogen is unclear, as is the mode of TTV transmission. To determine the prevalence of TTV infection and the possible fecal-oral route of transmission, we analyzed fecal specimens from 67 healthy, nontransfused children for TTV DNA sequences by heminested PCR, using the NG and T primer sets. The overall prevalence of TTV fecal excretion was 22.4% (15 of 67), with the T primer set (19.4%) being more sensitive than the NG primer set (10.4%). TTV prevalence based on gender or ethnicity showed no significant differences. None of seven children in the 0- to 6-month age group had detectable TTV in feces. Of three sets of siblings, two unrelated sets of twins, ages 33 and 37 months, were negative for fecal TTV DNA, while the third set of siblings, ages 99 and 35 months, was positive. The absence of TTV in the feces of children younger than 6 months and the high prevalence (40%) in children 7 to 12 months of age is consistent with age-specific acquisition of TTV infection by the nonparenteral route. TTV genotypes 1, 3, 4, and 5 were represented in our study population. TTV-positive siblings had TTV genotypes 1 and 4, suggesting unrelated environmental sources of TTV infection. This observation suggests a possible time frame for TTV acquisition in children which coincides with increased interaction with their environment and increased susceptibility to infectious agents.
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Affiliation(s)
- C L Lin
- Retrovirology Research Laboratory, Pacific Biomedical Research Center, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
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23
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Campo N, Brizzolara R, Sinelli N, Torre F, Russo R, Deferrari G, Picciotto A. TT virus infection in haemodialysis patients. Nephrol Dial Transplant 2000; 15:1823-6. [PMID: 11071972 DOI: 10.1093/ndt/15.11.1823] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The recent discovery of a new parenterally transmitted DNA virus called TT virus (TTV) led us to investigate its prevalence in haemodialysis patients, a high-risk group for blood-borne infection, and to evaluate its role in liver disease. Moreover, we compared the TTV prevalence with the prevalence of other hepatitis virus coinfections. METHODS Serum samples of 78 patients on maintenance haemodialysis were tested for TTV-DNA, hepatitis G virus (HGV)-RNA, anti-E2, anti-hepatitis C virus (HCV) and HCV-RNA. TTV-DNA was detected by semi-nested PCR using the primers from open reading frame 1 (ORF). HGV-RNA was detected by PCR using specific primers for the NS3 and the 5'-UTR genome regions while anti-E2 were checked by an enzyme immunological test. Anti-HCV was tested by the second generation Chiron RIBA HCV test system. HCV-RNA was evaluated by nested PCR with primers directed to the highly conserved 5' non-coding region of the HCV genome. RESULTS TTV prevalence in our patients was 19% (15/78) while the prevalence of HCV and HGV infection proved to be 20 and 15.4%, respectively. Among TTV positive patients HGV co-infection was present in five cases (33%), HCV in six cases (39.9%), while HBV co-infection was not present in any of the patients. Only three patients proved positive for all three viruses. ALT levels were normal in most cases (13/15; 86%). In particular, patients with TTV infection alone showed normal ALT levels and HCV coinfection was found in the two patients with moderate ALT increases. CONCLUSIONS TTV prevalence in haemodialysed patients is significant though the real clinical impact is still unclear. However, we must keep in mind that the epidemiological relevance of TTV infection is probably underestimated due to the impossibility in detecting the corresponding antibody.
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Affiliation(s)
- N Campo
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa, Italy
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24
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Yokosuka O, Ikeuchi T, Kanda T, Kawai S, Imazeki F, Saisho H, Mazzalli M, Filho GA, Nishimura NF, Soares EC. The prevalence of TT virus infection in renal transplant recipients in Brazil. Transplantation 2000; 70:1194-7. [PMID: 11063340 DOI: 10.1097/00007890-200010270-00012] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Recently, TT virus (TTV) was discovered as a potential causative agent for non-A-E hepatitis. Little is known about the prevalence of TTV infection in renal transplant recipients. METHODS One hundred and seventeen Brazilian renal transplant recipients and 100 normal subjects were examined to determine the prevalence of TTV infection. The TTV DNA in serum and its genotype were examined using polymerase chain reaction and restriction enzyme length polymorphism, respectively. RESULTS TTV DNA was detected in 63/117 (53.8%) renal transplant recipients in contrast to its detection in 10/100 (10%) normal subjects (P<0.001). There was no statistical difference in the distribution of TTV genotypes between these groups. There was no significant difference in clinical backgrounds between TTV positive and negative patients. CONCLUSIONS These results indicate a risk for TTV infection in renal transplant recipients in Brazil. They also indicate that TTV itself might not have a strong correlation with the pathogenicity of liver diseases.
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Affiliation(s)
- O Yokosuka
- First Department of Medicine, Chiba University School of Medicine, Japan
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25
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Bruno R, Sacchi P, Debiaggi M, Patruno SF, Zara F, Ciappina V, Brunetti E, Filice C, Zocchetti C, Maffezzini E, Pistorio A, Filice G. Prevalence and histologic features of transfusion transmitted virus and hepatitis C virus coinfection in a group of HIV patients. Dig Liver Dis 2000; 32:617-20. [PMID: 11142562 DOI: 10.1016/s1590-8658(00)80846-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND A recently identified DNA transfusion-transmitted virus has been associated with post-transfusion non-A to G hepatitis. AIM To determine the prevalence of transfusion-transmitted virus in patients with human immunodeficiency virus infection. Its clinical role in the pathogenesis of liver disease was also evaluated in patients with transfusion-transmitted-virus hepatitis C virus coinfection compared with those with hepatitis C Virus infection alone. PATIENTS AND METHODS We evaluated 312 HIV-hepatitis C virus coinfected patients (225 males, 87 females). All underwent screening for transfusion-transmitted virus DNA using a nested polymerase chain reaction technique. In some transfusion transmitted virus-DNA positive patients, we performed a phylogenetic analysis. In 56 patients (20 transfusion-transmitted-virus-hepatitis C virus and 36 hepatitis C virus alone), liver biopsy was collected. RESULTS The prevalence of transfusion-transmitted virus was 113/312 (36%). The genotype distribution was similar to that reported in other studies. No difference in liver histology was found between the two groups. CONCLUSION Transfusion-transmitted virus infection is common in human immunodeficiency virus patients. We found no histologic differences between liver biopsy specimens from patients coinfected with transfusion-transmitted virus plus hepatitis C virus compared with those infected with hepatitis C virus alone. Transfusion-transmitted virus is not clearly associated with a distinct liver injury.
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Affiliation(s)
- R Bruno
- Division of Infectious and Tropical Diseases, University of Pavia, IRCCS S. Matteo, Pavia, Italy.
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26
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Martínez NM, García F, García F, Alvarez M, Bernal MC, Piédrola G, Hernández J, Maroto MC. TT virus DNA in serum, peripheral blood mononuclear cells and semen of patients infected by HIV. AIDS 2000; 14:1464-6. [PMID: 10930170 DOI: 10.1097/00002030-200007070-00028] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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de Martino M, Moriondo M, Azzari C, Resti M, Galli L, Vierucci A. TT virus infection in human immunodeficiency virus type 1 infected mothers and their infants. J Med Virol 2000; 61:347-51. [PMID: 10861644 DOI: 10.1002/1096-9071(200007)61:3<347::aid-jmv11>3.0.co;2-s] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Serum TT virus (TTV) DNA was determined in 83 human immunodeficiency virus type 1 (HIV 1) infected mothers [46 intravenous drug user and 37 non-intravenous drug user women] and their infants. Twenty-nine (34.9%) mothers were TTV infected. Infection was more frequent among intravenous drug user than non-intravenous drug user mothers [21/46 (45.6%) vs. 8/37 (21.6%); relative risk (RR): 2.1; 95% confidence limits (95% CL): 1.1-4.2; P = 0.023] and among intravenous drug users who carried on injecting than in those who had given it up [10/14 (71.4%) vs. 11/32 (34.3%); RR: 2.1 (95%CL: 1.2-3.7); P = 0. 021]. Infection was not related to age, CD4-positive T-lymphocyte counts, HIV 1 load, hepatitis B (HBV), G/GB-C (GBV-C/HGV), C (HCV) virus exposure. Eight (27.5%) infants born to TTV infected (but none of those born to TTV uninfected) mothers were TTV infected at a median age of 1.5 (range: 0.6-2.8) months. Infants born by vaginal/emergency caesarean delivery were more frequently infected than those born by elective caesarean delivery [7/16 (43.7%) vs. 1/13 (7.6%); RR: 2.1; 95%CL: 1.2-3.5; P = 0.033]. Infection in infants was not related to maternal CD4-positive T-lymphocyte counts, HIV 1 load, and HIV 1, HBV, GBV-C/HGV, or HCV transmission. No infant became TTV infected thereafter. No TTV infected child [follow-up: 31 (median; range: 6-60) months] showed signs of liver disease; five infants cleared TTV DNA after 22 (median; range: 6-60) months. TTV infection in HIV 1 infected women is prevalently related to intravenous drug user. The findings suggest that infants may acquire TTV at birth. Infection may persist without evident liver disease.
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Affiliation(s)
- M de Martino
- Department of Paediatrics, University of Florence, Florence, Italy.
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28
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Springfeld C, Bugert JJ, Schnitzler P, Tobiasch E, Kehm R, Darai G. TT virus as a human pathogen: significance and problems. Virus Genes 2000; 20:35-45. [PMID: 10766305 DOI: 10.1023/a:1008156022845] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
In 1997 TTV was detected using representational difference analysis (RDA) in serum of a patient with posttransfusion hepatitis unrelated to known hepatitis viruses. The genome of TTV is a circular single-stranded DNA molecule of 3852 nt with negative polarity. TTV possibly can be grouped either into the existing family Circoviridae or into a recently established virus family "Circinoviridae". Analysis of the complete DNA nucleotide sequence of TTV identified three partially overlapping open reading frames (ORFs). Neither DNA nucleotide nor corresponding amino acid sequences of TTV do show significant homologies to known sequences. TTV DNA nucleotide sequences amplified by PCR from sera of different patients show considerable sequence variations. Although the natural route of transmission of TTV is still unknown, there is clear evidence for a transmission of TTV through blood and blood products. TTV DNA can be detected in the feces of infected individuals suggesting that it may be possible to attract TTV infection from environmental sources. Since the discovery of TTV, numerous studies have investigated the prevalence of TTV infections in different human population groups all over the world. All these studies are based on PCR detection systems, but the technical aspects of the PCR systems vary significantly between the different investigators. The results of the epidemiological studies do not show a clear picture. The discovery of TTV as a viral agent and particularly the identification of a high percentage of infected carriers in the healthy human population raises the following questions: Firstly, what is the origin and molecular relatedness of TT virus. Secondly, what is the significance of TTV as a human pathogen. And thirdly, what are the exact molecular mechanisms of viral replication. To answer these questions it will be necessary to determine the primary structure and the coding capacity of several TTV patient isolates.
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Affiliation(s)
- C Springfeld
- Institut für Medizinische Virologie der Ruprecht-Karls-Universität Heidelberg, Federal Republic of Germany
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29
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Biagini P, Attoui H, Gallian P, Touinssi M, Cantaloube JF, de Micco P, de Lamballerie X. Complete sequences of two highly divergent european isolates of TT virus. Biochem Biophys Res Commun 2000; 271:837-41. [PMID: 10814548 DOI: 10.1006/bbrc.2000.2721] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
TT virus is a virus distantly related to the Circoviridae family. We report here the complete genome characterization of two European human isolates (T3PB and TUPB) using a new and simple protocol for sequencing GC-rich genomic regions. Sequence analysis confirmed the existence of two major ORFs, of a CAV-like VP2 motif in ORF2 and of potential stem-loop structures in non-coding regions. Phylogenetic analyses based on complete genomic sequences of human isolates suggested that three different lineages exist at least. The first lineage includes genotypes 1, 2, and 3, and two other lineages include viruses related to the Japanese SANBAN and to the North American TUS01 isolates respectively. Sequence comparison made it possible to assign strain T3PB to genotype 3, and strain TUPB to the TUS01 group. Consequently, this study reports the first full-length sequence of a genotype 3 isolate and demonstrates that viruses belonging to the TUS01 lineage are present in the Old Word.
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Affiliation(s)
- P Biagini
- Laboratoire de Virologie Moléculaire, Etablissement François du Sang "Alpes-Méditerranée,", Unité des Virus Emergents, 149, Bd Baille, Marseille, 13005, France
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Biagini P, Gallian P, Touinssi M, Cantaloube JF, Zapitelli JP, de Lamballerie X, de Micco P. High prevalence of TT virus infection in French blood donors revealed by the use of three PCR systems. Transfusion 2000; 40:590-5. [PMID: 10827265 DOI: 10.1046/j.1537-2995.2000.40050590.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The purpose of this study was to determine the prevalence of TT virus (TTV) infection in voluntary blood donors in Southeastern France. STUDY DESIGN AND METHODS The sera of 289 blood donors were tested for the presence of TTV DNA by two PCR systems detecting genes located in the 5' UTR (primer set A [Set A]) and the open reading frame (ORF2) (primer set B [Set B]) of the viral genome. A randomized sample of 40 blood donors was also tested by a nested-PCR system in the ORF1 by use of primer set C (Set C). Donors were questioned for possible risk factors for virus transmission. RESULTS In the entire population studied, 30.8 percent of blood donors tested positive with both Sets A and B, and 70.6 percent with at least one set. In the sample tested with three sets of primers, 27.5 percent of blood donors were positive in testing with all PCR systems and 80 percent with at least one system. The specificity of TTV DNA amplification was confirmed by sequencing 10 PCR products obtained with each set of primers. Statistical analysis revealed that the prevalence of TTV reactivity increased with age. CONCLUSION The high prevalence of TTV reactivity and the absence of a pathologic condition or risk factors obviously associated with the infection in blood donors suggest that there is no need for systematic detection of TTV infection before blood donation. Further studies are required to determine if TTV isolates can be responsible for a pathologic condition in humans after blood transfusion.
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Affiliation(s)
- P Biagini
- Department of Molecular Virology, Marseille, France
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Huang YH, Wu JC, Lin CC, Sheng WY, Lee PC, Wang YJ, Chang FY, Lee SD. Prevalence and risk factor analysis of TTV infection in prostitutes. J Med Virol 2000; 60:393-5. [PMID: 10686021 DOI: 10.1002/(sici)1096-9071(200004)60:4<393::aid-jmv5>3.0.co;2-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
TTV, a DNA virus, has been isolated from patients with non-A to non-E post-transfusion hepatitis. In the past it was assumed that TTV was transmitted parenterally. It is unclear whether sexual contact leads to transmission of this virus. In this study, two sets of TTV-specific polymerase chain reaction primers were used to detect serum TTV DNA in 140 prostitutes and 136 controls. The prevalence of TTV DNA in prostitutes was significantly higher than in the control group (46/140 [32.9%] vs. 29/136 [21.3%]; P = 0.043). There was no significant difference in the prevalence of positive antibody to hepatitis A virus (anti-HAV) in either group (87.8% for prostitutes, 85.3% for controls). No particular risk factor was significantly associated with positive TTV DNA in prostitutes. In summary, TTV is highly prevalent in prostitutes. Transmission of TTV via sexual contact is not as efficient as transmission of hepatitis C and D viruses and GB virus-C hepatitis G virus. The high prevalence of TTV in controls indicates that there are diverse routes of transmission of this virus.
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Affiliation(s)
- Y H Huang
- Institute of Clinical Medicine, National Yang-Ming University, School of Medicine, Taipei, Taiwan, Republic of China
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Abstract
Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA-positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA-positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)
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Natural history of the TT virus infection through follow-up of TTV DNA–positive multiple-transfused patients. Blood 2000. [DOI: 10.1182/blood.v95.1.347] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA–positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA–positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)
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Deng X, Terunuma H, Handema R, Sakamoto M, Kitamura T, Ito M, Akahane Y. Higher prevalence and viral load of TT virus in saliva than in the corresponding serum: Another possible transmission route and replication site of TT virus. J Med Virol 2000. [DOI: 10.1002/1096-9071(200012)62:4<531::aid-jmv20>3.0.co;2-c] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Prevalence and Route of Transmission of Infection With a Novel DNA Virus (TTV), Hepatitis C Virus, and Hepatitis G Virus in Patients Infected With HIV. J Acquir Immune Defic Syndr 2000. [DOI: 10.1097/00042560-200001010-00012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Puig-Basagoiti F, Cabana M, Guilera M, Giménez-Barcons M, Sirera G, Tural C, Clotet B, Sánchez-Tapias JM, Rodés J, Saiz JC, Martínez MA. Prevalence and route of transmission of infection with a novel DNA virus (TTV), hepatitis C virus, and hepatitis G virus in patients infected with HIV. J Acquir Immune Defic Syndr 2000; 23:89-94. [PMID: 10708061 DOI: 10.1097/00126334-200001010-00012] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To evaluate the prevalence, route of transmission and clinical significance that current co-infection with TT virus (TTV), hepatitis C virus (HCV), and hepatitis G virus (HGV) have in HIV-1-infected patients. DESIGN Presence of TTV, HCV, and HGV was analyzed in plasma samples from 160 HIV-1-infected patients with parenteral (38 intravenous drug users [IVDUs] and 41 patients with hemophilia) or sexual (39 homosexuals and 42 heterosexuals) risk of exposure, and in 168 volunteer blood donors. Alanine aminotransferase (ALT) levels and CD4+ counts were also analyzed. METHODS HCV and HGV RNA were detected by specific reverse transcriptase (RT) nested polymerase chain reaction (PCR) and TTV DNA by specific heminested PCR. RESULTS TTV DNA was detected in 39% of the patients and in 14% of the volunteer blood donors. HCV and HGV infections were detected in 42% and in 14% of the patients, and in 0% and 3% of the blood donors, respectively. Prevalences of TTV and HCV infection were higher among patients with parenteral (62% and 68%) than in those with sexual (17% and 16%) risk of exposure. A higher prevalence of TTV infection (but not of HCV or HGV infection) was observed among patients with hemophilia (76%) than IVDUs (47%), and among homosexuals (26%) than among heterosexuals (10%). Abnormal ALT levels were related with the presence of HCV infection, independently of the detection of TTV DNA. TTV infection did not seem to alter the levels of CD4+ T cells. CONCLUSIONS Prevalence of current TTV infection is high among HIV-infected patients with parenteral risk of exposure, but TTV is also transmitted through sexual routes; detection of TTV does not seem to influence the clinical or immune status of HIV-infected patients.
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Affiliation(s)
- F Puig-Basagoiti
- Department of Medicine, Institut d'Investigacions Biomèdiques August Pí i Sunyer, Facultad de Medicina, Universidad de Barcelona, Spain
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Mason AL. TT virus: will work for food? Am J Gastroenterol 1999; 94:3398-401. [PMID: 10606288 DOI: 10.1111/j.1572-0241.1999.01658.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Nerurkar VR, Woodward CL, Nguyen HT, DeWolfe Miller F, Tashima LT, Zalles-Ganley A, Chua PK, Peterson JE, Chi PK, Hoang LT, Detels R, Yanagihara R. Lack of association between acquisition of TT virus and risk behavior for HIV and HCV infection in Vietnam. Int J Infect Dis 1999; 3:181-5. [PMID: 10575145 DOI: 10.1016/s1201-9712(99)90021-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND The search for the cause of chronic hepatitis among individuals with non-A to G hepatitis has led to the discovery of a post-transfusion hepatitis-related DNA virus, designated TT virus (TTV), which, based on viral sequences, belongs to a new virus family. The principal modes of infection with TTV are poorly understood, and its role in human immunodeficiency virus type 1 (HIV-1) infection is unclear. OBJECTIVE To determine if injection drug use (IDU) and high-risk heterosexual activity (HRHA), principal modes of acquiring HIV-1 infection, place individuals at greater risk of acquiring TTV. METHODS The authors analyzed DNA, extracted from sera or filter paper-blotted whole blood, obtained during August 1997 and June 1998 from 324 Vietnamese (148 male; 176 female), for TTV sequences by hot-start, heminested polymerase chain reaction. RESULTS Prevalence of TTV viremia was similar among individuals engaging in IDU or HRHA (23.4% vs. 20.2%; P > 0.5), with no age- or gender-specific differences. No association was found between TTV viremia and co-infection with HIV-1 or hepatitis C virus (HCV). Phylogenetic analysis of 30 TTV sequences revealed two distinct genotypes and four subtypes that did not segregate according to gender, HIV-1 and HCV risk behaviors, or geographic residence. CONCLUSIONS Among HIV-1- or HCV-infected Vietnamese, who presumably acquired their infection by either the parenteral or nonparenteral route, the data indicate no clear association between acquisition of TTV infection and risk behavior for HIV-1 or HCV infection, suggesting that the usual route of TTV transmission in Vietnam is other than parenteral or sexual.
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Affiliation(s)
- V R Nerurkar
- Retrovirology Research Laboratory, Pacific Biomedical Research Center, University of Hawaii at Manoa, Honolulu, Hawaii 96816, USA.
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Verschoor EJ, Langenhuijzen S, Heeney JL. TT viruses (TTV) of non-human primates and their relationship to the human TTV genotypes. J Gen Virol 1999; 80 ( Pt 9):2491-2499. [PMID: 10501506 DOI: 10.1099/0022-1317-80-9-2491] [Citation(s) in RCA: 49] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Sera from eight different non-human primate species, in total 216 samples, were analysed for the presence of TT virus (TTV) sequences. A very high incidence of TTV infection was found in sera from both common chimpanzees and pygmy chimpanzees, 48.8% and 66.7%, respectively. Sequence analysis of PCR fragments from two pygmy chimpanzees and seven common chimpanzees resulted in a total of 14 different TTV sequences. Phylogenetic analysis, including human TTV of all known genotypes, revealed that: (i) TTV from pygmy chimpanzees are closely related to viruses from human genotypes 2 and 3; (ii) TTV sequences obtained from common chimpanzees cluster together with human TTV genotypes 5 and 6, the latter only at the protein level; (iii) TTV from the common chimpanzee subspecies Pan troglodytes verus and Pan troglodytes schweinfurthii cluster together, suggesting an ancient host-pathogen relationship before subspeciation 1.6 million years ago; and (iv) TTV of common and pygmy chimpanzees may have been acquired by these animals in different zoonotic events not longer than 2.5 million years ago.
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Affiliation(s)
- Ernst J Verschoor
- Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands1
| | - Susan Langenhuijzen
- Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands1
| | - Jonathan L Heeney
- Department of Virology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands1
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Tagger A, Donato F, Ribero ML, Binelli G, Gelatti U, Portera G, Albertini A, Fasola M, Chiesa R, Nardi G. A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma. The Brescia HCC Study. Hepatology 1999; 30:294-9. [PMID: 10385670 DOI: 10.1002/hep.510300115] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
We performed a case-control study to evaluate the association of a new human DNA virus named TT virus (TTV) with hepatocellular carcinoma (HCC). We recruited 174 subjects hospitalized for HCC (84% males; mean age: 64 years) and 118 patients hospitalized for non-liver diseases in Brescia, northern Italy, as controls (94% males; mean age: 66 years). TTV DNA was found in serum by polymerase chain reaction (PCR) in 26 cases (15%) and 11 controls (9.3%) (P >. 1). TTV group 2 infection was identified in 16 cases (61.5%) and 4 controls (36.4%) (P >.1) using a type-specific PCR method. Sequence analysis of 222 nt of TTV DNA demonstrated that the remaining 10 cases and 7 controls were all infected by group 1. The odds ratio (OR) for TTV-DNA positivity, adjusted for demographic variables, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and heavy alcohol intake was 1.8 (95% CI: 0.7-4.8; P >.1). The OR did not change when the analysis was restricted to 14 HCC cases and 56 controls who were negative for each known risk factor for HCC (OR = 1.7; 95% CI: 0.8-4.0). TTV-DNA positivity was not associated with transfusion history. The prevalence of TTV DNA was higher among HCC cases positive for HBsAg (10 of 38 [26.3%]) than among those positive for HCV RNA (8 of 62 [12.9%]) or negative for hepatitis B virus (HBV), HCV, and hepatitis G virus (HGV) infections (5 of 62 [8. 1%]) (P =.02). This study does not support the hypothesis of an association between TTV infection and HCC.
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Affiliation(s)
- A Tagger
- Istituto di Virologia, Biochimiche e Cellulari dell'Università di Sassari, Italy
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