scholarly journals Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Chi N. Chan ◽  
Benjamin Trinité ◽  
David N. Levy
Keyword(s):  
T Cells ◽  
Reverse Transcription ◽  
Cd4 T Cells ◽  
Dominant Role ◽  
Respiratory Syndrome Virus ◽  
Virus Protein ◽  
Activated T Cells ◽  
Herpes Simplex Viruses ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT HIV-1 infection of resting CD4 T cells plays a crucial and numerically dominant role during virus transmission at mucosal sites and during subsequent acute replication and T cell depletion. Resveratrol and pterostilbene are plant stilbenoids associated with several health-promoting benefits. Resveratrol has been shown to inhibit the replication of several viruses, including herpes simplex viruses 1 and 2, papillomaviruses, severe acute respiratory syndrome virus, and influenza virus. Alone, resveratrol does not inhibit HIV-1 infection of activated T cells, but it does synergize with nucleoside reverse transcriptase inhibitors in these cells to inhibit reverse transcription. Here, we demonstrate that resveratrol and pterostilbene completely block HIV-1 infection at a low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, an HIV-1 and simian immunodeficiency virus protein that increases deoxynucleoside triphosphate (dNTP) levels. These findings are consistent with the reported ability of resveratrol to inhibit ribonucleotide reductase and to lower dNTP levels in cells. This study supports the potential use of resveratrol, pterostilbene, or related compounds as adjuvants in anti-HIV preexposure prophylaxis (PrEP) formulations.

An Effective Vaccination Approach Augments Anti-HIV Systemic and Vaginal Immunity in Mice with Decreased HIV-1 Susceptible α4β7high CD4+ T Cells

2013 ◽  
Vol 11 (1) ◽  
pp. 56-66
Author(s):  
Wei Zhu ◽  
Guoping Shi ◽  
Haijun Tang ◽  
Dorothy E. Lewis ◽  
Xiao-Tong Song
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Vaginal Immunity

scholarly journals The critical role of human transcriptional repressor CTCF mRNA up-regulation in the induction of anti-HIV-1 responses in CD4+ T cells

2008 ◽  
Vol 117 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Yuchang Li ◽  
Guanhua Li ◽  
Anna Ivanova ◽  
Sagiv Aaron ◽  
Malgorzata Simm
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Transcriptional Repressor ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Alpha Interferon Potently Enhances the Anti-Human Immunodeficiency Virus Type 1 Activity of APOBEC3G in Resting Primary CD4 T Cells

2006 ◽  
Vol 80 (15) ◽  
pp. 7645-7657 ◽  
Author(s):  
Keyang Chen ◽  
Jialing Huang ◽  
Chune Zhang ◽  
Sophia Huang ◽  
Giuseppe Nunnari ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Innate Immunity ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT The interferon (IFN) system, including various IFNs and IFN-inducible gene products, is well known for its potent innate immunity against wide-range viruses. Recently, a family of cytidine deaminases, functioning as another innate immunity against retroviral infection, has been identified. However, its regulation remains largely unknown. In this report, we demonstrate that through a regular IFN-α/β signal transduction pathway, IFN-α can significantly enhance the expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in human primary resting but not activated CD4 T cells and the amounts of APOBEC3G associated with a low molecular mass. Interestingly, short-time treatments of newly infected resting CD4 T cells with IFN-α will significantly inactivate human immunodeficiency virus type 1 (HIV-1) at its early stage. This inhibition can be counteracted by APOBEC3G-specific short interfering RNA, indicating that IFN-α-induced APOBEC3G plays a key role in mediating this anti-HIV-1 process. Our data suggest that APOBEC3G is also a member of the IFN system, at least in resting CD4 T cells. Given that the IFN-α/APOBEC3G pathway has potent anti-HIV-1 capability in resting CD4 T cells, augmentation of this innate immunity barrier could prevent residual HIV-1 replication in its native reservoir in the post-highly active antiretroviral therapy era.

scholarly journals A Cell-Intrinsic Inhibitor of HIV-1 Reverse Transcription in CD4+ T Cells from Elite Controllers

2014 ◽  
Vol 15 (6) ◽  
pp. 717-728 ◽  
Author(s):  
Jin Leng ◽  
Hsin-Pin Ho ◽  
Maria J. Buzon ◽  
Florencia Pereyra ◽  
Bruce D. Walker ◽  
...  
Keyword(s):  
T Cells ◽  
Reverse Transcription ◽  
Cd4 T Cells ◽  
Elite Controllers ◽  
A Cell ◽  
Hiv 1

scholarly journals SAMHD1 restricts HIV-1 reverse transcription in quiescent CD4+T-cells

Retrovirology ◽  
2012 ◽  
Vol 9 (1) ◽  
Author(s):  
Benjamin Descours ◽  
Alexandra Cribier ◽  
Christine Chable-Bessia ◽  
Diana Ayinde ◽  
Gillian Rice ◽  
...  
Keyword(s):  
T Cells ◽  
Reverse Transcription ◽  
Cd4 T Cells ◽  
Hiv 1

scholarly journals HIV-1 Vpr- and Reverse Transcription-Induced Apoptosis in Resting Peripheral Blood CD4 T Cells and Protection by Common Gamma-Chain Cytokines

2015 ◽  
Vol 90 (2) ◽  
pp. 904-916 ◽  
Author(s):  
Benjamin Trinité ◽  
Chi N. Chan ◽  
Caroline S. Lee ◽  
David N. Levy
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Reverse Transcription ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Productive Infection ◽  
Hiv 1

ABSTRACTHIV-1 infection leads to the progressive depletion of the CD4 T cell compartment by various known and unknown mechanisms.In vivo, HIV-1 infects both activated and resting CD4 T cells, butin vitro, in the absence of any stimuli, resting CD4 T cells from peripheral blood are resistant to infection. This resistance is generally attributed to an intracellular environment that does not efficiently support processes such as reverse transcription (RT), resulting in abortive infection. Here, we show thatin vitroHIV-1 infection of resting CD4 T cells induces substantial cell death, leading to abortive infection.In vivo, however, various microenvironmental stimuli in lymphoid and mucosal tissues provide support for HIV-1 replication. For example, common gamma-chain cytokines (CGCC), such as interleukin-7 (IL-7), render resting CD4 T cells permissible to HIV-1 infection without inducing T cell activation. Here, we find that CGCC primarily allow productive infection by preventing HIV-1 triggering of apoptosis, as evidenced by early release of cytochromecand caspase 3/7 activation. Cell death is triggered both by products of reverse transcription and by virion-borne Vpr protein, and CGCC block both mechanisms. When HIV-1 RT efficiency was enhanced by SIVmac239 Vpx protein, cell death was still observed, indicating that the speed of reverse transcription and the efficiency of its completion contributed little to HIV-1-induced cell death in this system. These results show that a major restriction on HIV-1 infection in resting CD4 T cells resides in the capacity of these cells to survive the early steps of HIV-1 infection.IMPORTANCEA major consequence of HIV-1 infection is the destruction of CD4 T cells. Here, we show that delivery of virion-associated Vpr protein and the process of reverse transcription are each sufficient to trigger apoptosis of resting CD4 T cells isolated from peripheral blood. While these 2 mechanisms have been previously described in various cell types, we show for the first time their concerted effect in inducing resting CD4 T cell depletion. Importantly, we found that cytokines such as IL-7 and IL-4, which are particularly active in sites of HIV-1 replication, protect resting CD4 T cells from these cytopathic effects and, primarily through this protection, rather than through enhancement of specific replicative steps, they promote productive infection. This study provides important new insights for the understanding of the early steps of HIV-1 infection and T cell depletion.

scholarly journals Methamphetamine Inhibits HIV-1 Replication in CD4+ T Cells by Modulating Anti–HIV-1 miRNA Expression

2014 ◽  
Vol 184 (1) ◽  
pp. 92-100 ◽  
Author(s):  
Chinmay K. Mantri ◽  
Jyoti V. Mantri ◽  
Jui Pandhare ◽  
Chandravanu Dash
Keyword(s):  
T Cells ◽  
Mirna Expression ◽  
Cd4 T Cells ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Histone deacetylase 1 interacts with HIV-1 Integrase and modulates viral replication

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Fadila Larguet ◽  
Clément Caté ◽  
Benoit Barbeau ◽  
Eric Rassart ◽  
Elsy Edouard
Keyword(s):  
Mass Spectrometry ◽  
T Cells ◽  
Host Cell ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Reverse Transcription ◽  
Cd4 T Cells ◽  
Histone Deacetylase 1 ◽  
Binding Partners ◽  
Hiv 1

Abstract Background HIV-1 hijacks the cellular machinery for its own replication through protein-protein interactions between viral and host cell factors. One strategy against HIV-1 infection is thus to target these key protein complexes. As the integration of reverse transcribed viral cDNA into a host cell chromosome is an essential step in the HIV-1 life cycle, catalyzed by the viral integrase and other important host factors, we aimed at identifying new integrase binding partners through a novel approach. Methods A LTR-derived biotinylated DNA fragment complexed with the integrase on magnetic beads was incubated with extracts from integrase-expressing 293 T cells. Liquid chromatography-mass spectrometry/mass spectrometry and co-immunoprecipitation/pull-down experiments were used for the identification of binding partners. Transfections of histone deacetylase 1 (HDAC1) expression vectors and/or specific siRNA were conducted in HeLa-CD4 and 293 T cells followed by infection with fully infectious NL4–3 and luciferase-expressing pseudotyped viruses or by proviral DNA transfection. Fully infectious and pseudotyped viruses produced from HDAC1-silenced 293 T cells were tested for their infectivity toward HeLa-CD4 cells, T cell lines and primary CD4+ T cells. Late RT species and integrated viral DNA were quantified by qPCR and infectivity was measured by luciferase activity and p24 ELISA assay. Results were analyzed by the Student’s t-test. Results Using our integrase-LTR bait approach, we successfully identified new potential integrase-binding partners, including HDAC1. We further confirmed that HDAC1 interacted with the HIV-1 integrase in co-immunoprecipitation and pull-down experiments. HDAC1 knockdown in infected HeLa cells was shown to interfere with an early preintegration step of the HIV-1 replication cycle, which possibly involves reverse transcription. We also observed that, while HDAC1 overexpression inhibited HIV-1 expression after integration, HDAC1 knockdown had no effect on this step. In virus producer cells, HDAC1 knockdown had a limited impact on virus infectivity in either cell lines or primary CD4+ T cells. Conclusions Our results show that HDAC1 interacts with the HIV-1 integrase and affects virus replication before and after integration. Overall, HDAC1 appears to facilitate HIV-1 replication with a major effect on a preintegration step, which likely occurs at the reverse transcription step.

Sign in / Sign up

Export Citation Format

Share Document