• HIV
• HIV life cycle
• T-helper cells
• cytokines
• viral transmission

• R01 DA041746 NIDA NIH HHS
• R21 MH126998 NIMH NIH HHS
• 1R21MH126998-01A1 to M.T. NIDA NIH HHS
• 1R01DA041746-01 to M.T. NIDA NIH HHS

• p53 modulation
• pathogenesis
• positive-strand RNA virus
• viral infection

• DBT-IISc partnership program
• Department of Biotechnology(DBT)
• Institute of Eminence (IoE), Post-doctoral fellowship program IISc
• J.C. Bose fellowship
• Ministry of Human Resource and Development (MHRD)

• HIV/AIDS
• Jian Aikang Concentrated Pill
• mechanism
• multi-pathway
• network pharmacology

• Acquired Immunodeficiency Syndrome/drug therapy
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Humans
• Immunity
• Interleukin-10
• Interleukin-6
• Molecular Docking Simulation
• Network Pharmacology/methods
• RNA, Messenger

• the National Natural Science Foundation of China

• HIV
• HIV-1 vaccine
• IgG
• antibodies
• catalytic antibodies
• neutralizing antibodies
• vaccine
• viral envelope

• 20-34-70115 Russian Foundation for Basic Research
• 21-75-10105 Russian Science Foundation

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result of sustained HIV replication in the CNS even in the face of combination antiretroviral therapy, there is a high incidence of HIV-associated neurocognitive disorders (HAND). This article, therefore, provides a comprehensive review of HIV transcriptional regulation, latency, and therapy in the CNS.

• HIV
• central nervous system
• latency
• therapy
• transcriptional regulation

• R01 DA041746 NIDA NIH HHS
• 1R01DA041746-01 to M.T NIDA NIH HHS

• ARV associated hepatotoxicity
• Cytokine
• Genetic polymorphism
• HIV patients
• IL-2 gene
• NNRTI regimen.

Human immunodeficiency virus-1 (HIV-1) has the ability to infect latently at the level of individual CD4+ cells. Latent HIV-1 proviruses are transcriptionally silent and immunologically inert, but are still capable of reactivating productive lytic infection following cellular activation. These latent viruses are the main obstacle in the eradication of HIV-1, because current HIV-1 treatment regimens are ineffective against them. Normal immunological response against an antigen activates CD4+ naïve T cells. The activated CD4+ naïve T cells undergo cell cycle, resulting in further transformation and profound proliferation to form effector CD4+ T-cells. Notably, in HIV-1 infected individuals, some of the effector CD4+ T cells get infected with HIV-1. Upon fulfillment of their effector functions, almost all activated CD4+ T cells are committed to apoptosis or programmed cell death, but a miniscule fraction revert to quiescence and become resting memory CD4+ T cells to mediate a rapid immunological response against the same antigen in the future. However, due to the quiescent nature of the resting memory T cells, the integrated HIV-1 becomes transcriptionally silent and acquires a latent phenotype. Following re-exposure to the same antigen, memory cells and integrated HIV-1 are stimulated. The reactivated latent HIV provirus subsequently proceeds through its life cycle and eventually leads to the production of new viral progeny. Recently, many strategies against HIV-1 latency have been developed and some of them have even matured to the clinical level, but none can yet effectively eliminate the latent HIV reservoir, which remains a barrier to HIV-1 cure. Therefore, alternative strategies to eradicate latent HIV need to be considered. This review provides vital knowledge on HIV latency and on strategies to supplement highly active anti-retroviral therapy (HAART) with cytokine-mediated therapeutics for dislodging the latent HIV reservoirs in order to open up new avenues for curing HIV.

• HIV-1
• eradication
• latency
• resting memory CD4+ T-cells
• transforming growth factor-beta (TGF-β)

• aids
• hiv infection
• pulmonary sarcoidosis

• Aged
• Female
• HIV Infections/complications
• Humans
• Sarcoidosis, Pulmonary/complications

CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells in an in vitro model of quiescent CD4 T cells. Here we show that stimulation of CD4+ T cells with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression of CD32 and the activation of the markers HLA-DR and CD69. HIV-1 infection increases CD32 expression. 79.2% of the CD32+/CD4+ T cells from HIV+ individuals under antiretroviral treatment were HLA-DR+. Resting CD4+ T cells infected in vitro generally results in higher integration of provirus. We observe no difference in provirus integration or replication-competent inducible latent HIV-1 in CD32+ or CD32− CD4+ T cells from HIV+ individuals. Our results demonstrate that CD32 expression is a marker of CD4+ T cell activation in HIV+ individuals and raises questions regarding the immune resting status of CD32+ cells harboring HIV-1 proviruses.

CD32 has been previously shown to be expressed preferentially by CD4 T cells latently harbouring HIV-1. Here the authors show that CD32 expression in CD4 T cells is associated with T cell activation, is up-regulated by HIV-1 infection and importantly does not appear to represent an enriched cellular niche for latent HIV-1.

The discovery of the tumor suppressor p53, through its interactions with proteins of tumor-promoting viruses, paved the way to the understanding of p53 roles in tumor virology. Over the years, accumulating data suggest that WTp53 is involved in the viral life cycle of non-tumor-promoting viruses as well. These include the influenza virus, smallpox and vaccinia viruses, the Zika virus, West Nile virus, Japanese encephalitis virus, Human Immunodeficiency Virus Type 1, Human herpes simplex virus-1, and more. Viruses have learned to manipulate WTp53 through different strategies to improve their replication and spreading in a stage-specific, bidirectional way. While some viruses require active WTp53 for efficient viral replication, others require reduction/inhibition of WTp53 activity. A better understanding of WTp53 functionality in viral life may offer new future clinical approaches, based on WTp53 manipulation, for viral infections.

• HIV-1
• HSV-1
• SV40
• cancer
• influenza
• p53
• papilloma
• vaccinia
• virus
• zika

• Alternative Splicing/genetics
• Apoptosis
• Bystander Effect/immunology
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/virology
• Cell Line, Tumor
• Cell Membrane/immunology
• Cellular Microenvironment/immunology
• HEK293 Cells
• HIV Infections/immunology
• HIV Infections/pathology
• HIV Infections/virology
• HeLa Cells
• Humans
• Jurkat Cells
• Protein Isoforms/biosynthesis
• Protein Isoforms/genetics
• Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism
• TNF-Related Apoptosis-Inducing Ligand/biosynthesis
• TNF-Related Apoptosis-Inducing Ligand/genetics

• R01 AI110173 NIAID NIH HHS
• R01 AI120698 NIAID NIH HHS
• R56 AI120698 NIAID NIH HHS

Follicular CD4+ T helper (TFH) cells interact with B cells in follicular germinal centers and play a prominent role in promoting effective humoral immune responses to pathogens, providing help for B cell development and antibody affinity maturation. Recent studies indicate TFH cells are expanded in HIV/SIV chronic infection, or depleted in terminal stages of disease, yet relatively maintained in elite controllers when compared with uninfected controls. A better understanding of the mechanisms behind these immunologic abnormalities may lead to more effective vaccination and therapeutic strategies. Here, we review recent findings of TFH cells in HIV/SIV infection and discuss the correlation of changes and function of TFH cells with host immunity. Dysregulation or depletion of CD4+ TFH cells likely plays a major role in the inability of HIV-infected patients to mount effective immune responses.

• HIV
• SIV
• TFH cells
• follicular CD4 T helper cells
• immunity

• cat
• chimeric antibody
• monoclonal antibody
• tumor necrosis factor-alpha

• Animals
• Antibodies, Monoclonal/immunology
• Antibodies, Monoclonal/isolation & purification
• Blotting, Western
• Cats/immunology
• Chimera/immunology
• Cloning, Molecular
• Enzyme-Linked Immunosorbent Assay
• Mice
• Neutralization Tests
• Tumor Necrosis Factor-alpha/immunology

• Adolescent
• Anti-Retroviral Agents/therapeutic use
• CD4 Lymphocyte Count
• Child
• Child, Preschool
• DNA, Circular
• Disease Progression
• Female
• GRB2 Adaptor Protein/immunology
• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/immunology
• HIV Infections/drug therapy
• HIV Infections/immunology
• HIV-1/immunology
• Humans
• Infant
• Interleukin-8/biosynthesis
• Interleukin-8/immunology
• Leukocytes, Mononuclear
• Male
• RNA, Messenger
• Real-Time Polymerase Chain Reaction
• Receptors, Interleukin-8A/biosynthesis
• Receptors, Interleukin-8A/immunology
• Viral Load

To determine how immune markers are affected by acute hypoxic exercise at the same relative intensity.

Twelve endurance-trained males (age: 28 ± 4 years, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}$$\end{document}V˙O_2max: 63.7 ± 5.3 mL/kg/min) cycled for 75 min at 70 % of altitude-specific \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\dot{V}$$\end{document}V˙O_2max, once in normoxia (N) and once in hypobaric hypoxia equivalent to 2000 m above sea-level (H). Blood and saliva samples were collected pre-, post- and 2 h post-exercise.

Participants cycled at 10.5 % lower power output in H vs. N, with no significant differences in heart rate (P = 0.10) or rating of perceived exertion (P = 0.21). Post-exercise plasma cortisol was higher in H vs. N [683 (95 % CI 576–810) nmol/l vs. 549 (469–643) nmol/l, P = 0.017]. The exercise-induced decrease in CD4:CD8 ratio was greater in H vs. N (−0.5 ± 0.2 vs. −0.3 ± 0.2, P = 0.019). There were no significant between-trial differences for adrenocorticotropic hormone, plasma cytokines, antigen-stimulated cytokine production, salivary immunoglobulin-A or lactoferrin. However, there was a main trial effect for concentration [F(11) = 5.99, P < 0.032] and secretion [F(11) = 5.01, P < 0.047] of salivary lysozyme, with this being higher in N at every time-point.

Whether the observed differences between H and N are of sufficient magnitude to clinically impair host defence is questionable, particularly as they are transient in nature and since other immune markers are unaffected. As such, acute hypoxic exercise likely does not pose a meaningful additional threat to immune function compared to exercise at sea level, provided that absolute workload is reduced in hypoxia so that relative exercise intensity is the same.

• Altitude
• Cortisol
• Cytokine
• Endurance
• Lymphocytes
• S-IgA

• Adult
• Altitude Sickness/immunology
• Cytokines/blood
• Cytokines/immunology
• Exercise
• Humans
• Immunity, Mucosal/immunology
• Immunologic Factors/blood
• Immunologic Factors/immunology
• Male
• Physical Endurance/immunology
• Stress, Physiological/immunology

• CD4+
• EC
• HIV
• HLA

Secondary lymphoid organs (SLOs) are sites that facilitate cell-cell interactions required for generating adaptive immune responses. Nonhematopoietic mesenchymal stromal cells have been shown to play a critical role in SLO function, organization, and tissue homeostasis. The stromal microenvironment undergoes profound remodeling to support immune responses. However, chronic inflammatory conditions can promote uncontrolled stromal cell activation and aberrant tissue remodeling including fibrosis, thus leading to tissue damage. Despite recent advancements, the origin and role of mesenchymal stromal cells involved in SLO development and remodeling remain unclear.

Feline infectious peritonitis virus (FIPV) replication in macrophages/monocytes induced tumor necrosis factor (TNF)-alpha production, and that the TNF-alpha produced was involved in aggravating the pathology of FIP. We previously reported the preparation of a feline TNF-alpha (fTNF-alpha)-neutralizing mouse monoclonal antibody (anti-fTNF-alpha mAb). This anti-fTNF-alpha mAb 2–4 was confirmed to inhibit the following fTNF-alpha-induced conditions in vitro. In the present study, we investigated whether mAb 2–4 improved the FIP symptoms and survival rate of experimentally FIPV-inoculated SPF cats. Progression to FIP was prevented in 2 out of 3 cats treated with mAb 2–4, whereas all 3 cats developed FIP in the placebo control group. Plasma alpha1-glycoprotein and vascular endothelial growth factor levels were improved by the administration of mAb 2–4, and the peripheral lymphocyte count also recovered. These results strongly suggested that the anti-fTNF-alpha antibody is effective for the treatment of FIP.

•

Feline infectious peritonitis (FIP) is a coronavirus-induced fatal disease in cats.

• Feline coronavirus
• Feline infectious peritonitis
• Tumor necrosis factor-alpha

• Animals
• Food Chain
• Linear Models
• Models, Biological
• Nonlinear Dynamics
• Population Dynamics
• Predatory Behavior
• Systems Analysis
• Systems Biology
• Systems Theory

• AIDS
• Lewis antigens
• Siglecs
• galectins
• immune evasion

• Animals
• Female
• Fetus/immunology
• HIV/chemistry
• HIV/immunology
• Helicobacter pylori/chemistry
• Helicobacter pylori/immunology
• Host-Pathogen Interactions
• Humans
• Immune Evasion
• Immune Tolerance
• Male
• Neoplasms/chemistry
• Neoplasms/immunology
• Neoplasms/pathology
• Polysaccharides/chemistry
• Polysaccharides/immunology
• Pregnancy
• Reproduction/immunology
• Schistosoma/chemistry
• Schistosoma/immunology
• Spermatozoa/chemistry
• Spermatozoa/immunology

The roles of Type I interferon (IFN) in human immunodeficiency virus Type 1 (HIV-1) neuropathogenesis are poorly understood; both protective and deleterious effects of IFN signaling have been described. We used genetically modified mice deficient in the Type I IFN receptor (IFNRKO) to analyze the progress of HIV-1 brain infection and neuropathogenesis in the absence of IFN signaling. IFNRKO and wild-type (WT) mice on the 129xSv/Ev or C57BL/6 strain backgrounds were infected systemically with EcoHIV, a chimeric HIV-1 that productively infects mice. IFNRKO mice showed higher HIV-1 expression in spleen and peritoneal macrophages and greater virus infiltration into the brain compared to WT mice. Neuropathogenesis was studied by histopathological, immunohistochemical, immunofluorescence, and polymerase chain reaction analyses of brain tissues after the virus was inoculated into the brain by stereotaxic intracerebral injection. Both IFNRKO and WT mice showed readily detectable HIV-1 and brain lesions, including microglial activation, astrocytosis, and increased expression of genes coding for inflammatory cytokines and chemokines typical of human HIV-1 brain disease. Parameters of HIV-1 neuropathogenesis, including HIV-1 expression in microglia/macrophages, were significantly greater in IFNRKO than in WT mice. Our results show unequivocally that Type I IFN signaling and responses limit HIV-1 infection and pathogenesis in the brains of mice.

• Feline coronavirus
• Feline infectious peritonitis
• Tumor necrosis factor-alpha

• CD4 Lymphocyte Count
• Cytokines/blood
• HIV Infections/blood
• HIV Infections/immunology
• HIV Infections/virology
• HIV-1/immunology
• Humans
• Male
• Semen/immunology
• Semen/metabolism
• Semen/virology
• Viral Load

• ZIA HD001416 Intramural NIH HHS
• ZIA HD001416-19 Intramural NIH HHS

• AIDS
• HIV
• IL-6
• alcohol
• race/ethnicity

HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.

In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.

CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 10⁵ ng/ml [0.2-42.4 × 10⁵] vs. 1.1 × 10⁵ [0.5-12.2 × 10⁵]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.

Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.

• Acquired Immunodeficiency Syndrome/blood
• Acquired Immunodeficiency Syndrome/complications
• Acquired Immunodeficiency Syndrome/drug therapy
• Anti-Retroviral Agents/therapeutic use
• Communicable Diseases/complications
• Communicable Diseases/drug therapy
• HIV Infections/blood
• HIV Infections/complications
• HIV Infections/drug therapy
• HIV-1/isolation & purification
• Herpes Simplex/complications
• Herpes Simplex/drug therapy
• Humans
• Malaria/complications
• Malaria/drug therapy
• Parasitic Diseases/complications
• Parasitic Diseases/drug therapy
• RNA, Viral/blood
• Syphilis/complications
• Syphilis/drug therapy
• Tuberculosis/complications
• Tuberculosis/drug therapy
• Viral Load/drug effects

• P30 AI054999 NIAID NIH HHS
• R03TW05929 FIC NIH HHS
• 5P30AI054999 NIAID NIH HHS
• R03 TW005929-02 FIC NIH HHS
• R03 TW005929 FIC NIH HHS
• T32GM00836 NIGMS NIH HHS

• Carrier Proteins/metabolism
• Cells, Cultured
• Cytokines/biosynthesis
• Cytokines/metabolism
• HIV-1/physiology
• Host-Pathogen Interactions
• Humans
• Leukocytes, Mononuclear/immunology
• Leukocytes, Mononuclear/virology
• Virus Replication

• Complementarity Determining Regions
• HIV Envelope Protein gp120/chemistry
• HIV Envelope Protein gp120/immunology
• HIV-1/immunology
• Humans
• T-Lymphocytes/immunology