Role of HIV-1 Tat in AIDS pathogenesis: its effects on cytokine dysregulation and contributions to the pathogenesis of opportunistic infection

Li, J.; Yim, Howard Chi Ho; Lau, Alan F.

doi:10.1097/qad.0b013e32833ac6a0

Cited by 43 publications

(43 citation statements)

References 153 publications

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“…Introduction of highly active anti-retroviral therapy (ART) in infected patients significantly slowed progression of disease to AIDS and the development of the most common and recurrent opportunistic infections— Pneumocystis carinii pneumonia (PCP), candidiasis, disseminated Mycobacterium avium complex (MAC) disease, toxoplasmosis, activation of cytomegalo-viral infection and other infections (Heaton et al 2010; Li et al 2010). …”

Section: Il-23 and Cd4+ Cell Subsets As A Target For Hiv-1mentioning

confidence: 99%

IL-23 in Infections, Inflammation, Autoimmunity and Cancer: Possible Role in HIV-1 and AIDS

Yannam

Gutti

Poluektova

2011

J Neuroimmune Pharmacol

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The growing family of interleukin (IL)-12-like cytokines produced by activated macrophages and dendritic cells became the important players in the control of infections, development of inflammation, autoimmunity and cancer. However, the role of one of them—heterodimer IL-23, which consists of IL12p40 and the unique p19 subunit in HIV-1 infection pathogenesis and progression to AIDS, represent special interest. We overviewed findings of IL-23 involvement in control of peripheral bacterial pathogens and opportunistic infection, central nervous system (CNS) viral infections and autoimmune disorders, and tumorogenesis, which potentially could be applicable to HIV-1 and AIDS.

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Section: Il-23 and Cd4+ Cell Subsets As A Target For Hiv-1mentioning

confidence: 99%

IL-23 in Infections, Inflammation, Autoimmunity and Cancer: Possible Role in HIV-1 and AIDS

Yannam

Gutti

Poluektova

2011

J Neuroimmune Pharmacol

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“…Upon release Tat binds heparan sulphate proteoglycans of the extracellular-matrix and is detected in tissues of infected individuals [40], [44]. Extracellular Tat exerts activities on both viral infection and immune activation that are key in acquisition of infection, as well as for virus reactivation and for HIV disease maintenance in HAART treated individuals [23], [31], [32], [38], [40], [42]–[51].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART

et al. 2010

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Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4+ and CD8+ cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4+ T cells and B cells with reduction of CD8+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4+ and CD8+ T cells were accompanied by increases of CD4+ and CD8+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the OBS population. These findings support the use of Tat immunization to intensify HAART efficacy and to restore immune homeostasis.Trial registrationClinicalTrials.gov NCT00751595

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“…Viruses have evolved to modulate the NF-kB pathway to enhance viral replication, improve host cell survival, and evade the immune response [39]. With HIV, viral and cellular membrane fusion activates NF-κB, a process that requires CD4 + T cells.…”

Section: Introductionmentioning

confidence: 99%

Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

et al. 2011

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BackgroundBovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays.ResultsThe cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action.HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-β-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV-1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours.ConclusionsbDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours.bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals.

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Role of HIV-1 Tat in AIDS pathogenesis: its effects on cytokine dysregulation and contributions to the pathogenesis of opportunistic infection

Cited by 43 publications

References 153 publications

IL-23 in Infections, Inflammation, Autoimmunity and Cancer: Possible Role in HIV-1 and AIDS

IL-23 in Infections, Inflammation, Autoimmunity and Cancer: Possible Role in HIV-1 and AIDS

Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART

Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection

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