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The major histocompatibility complex class II alleles Mamu-DRB11003 and -DRB10306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

ABSTRACT: The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.

SUBMITTER: Giraldo-Vela JP

PROVIDER: S-EPMC2224575 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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The major histocompatibility complex class II alleles Mamu-DRB11003 and -DRB10306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

Giraldo-Vela Juan P JP Rudersdorf Richard R Chung Chungwon C Qi Ying Y Wallace Lyle T LT Bimber Benjamin B Borchardt Gretta J GJ Fisk Debra L DL Glidden Chrystal E CE Loffredo John T JT Piaskowski Shari M SM Furlott Jessica R JR Morales-Martinez Juan P JP Wilson Nancy A NA Rehrauer William M WM Lifson Jeffrey D JD Carrington Mary M Watkins David I DI

Journal of virology 20071107 2

The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques contr ...[more]

PMID: 17989178

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Project description:Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to <10 SIV RNA copies/mL with ART, without viral blips. At ART cessation, initial rebound viremia to ~106 copies/mL was followed by a decline to < 10 copies/mL, suggesting effective immune control. Three post-treatment controller RMs received three doses of RMD every 35-50 days, followed by in vivo experimental depletion of CD8+ cells using monoclonal antibody M-T807R1. RMD was well-tolerated and resulted in a rapid and massive surge in T cell activation, as well as significant virus rebounds (~104 copies/ml) peaking at 5-12 days post-treatment. CD8+ cell depletion resulted in a more robust viral rebound (107 copies/ml) that was controlled upon CD8+ T cell recovery. Our results show that RMD can reactivate SIV in vivo in the setting of post-ART viral control. Comparison of the patterns of virus rebound after RMD administration and CD8+ cell depletion suggested that RMD impact on T cells is only transient and does not irreversibly alter the ability of SIV-specific T cells to control the reactivated virus.

Dataset Information

The major histocompatibility complex class II alleles Mamu-DRB11003 and -DRB10306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

Publications

The major histocompatibility complex class II alleles Mamu-DRB11003 and -DRB10306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

Publications

The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The major histocompatibility complex class II alleles Mamu-DRB11003 and -DRB10306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

The major histocompatibility complex class II alleles Mamu-DRB11003 and -DRB10306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.