Effects of alcohol consumption on antigen-specific cellular and humoral immune responses to SIV in rhesus macaques.

ABSTRACT: BACKGROUND:Simian immunodeficiency virus (SIV) infection in macaques chronically receiving ethanol results in significantly higher plasma viral loads and more rapid progression to end-stage disease. We thus hypothesized that the increased plasma viral load in ethanol-treated, SIV-infected macaques would negatively correlate with antigen-specific immune responses. METHODS:Rhesus macaques were administered ethanol or sucrose (n = 12 per group) by indwelling gastric catheters for 3 months and then intravenously infected with SIVMAC251. Peripheral blood T- and B-cell immunophenotyping and quantification were performed. Plasma was examined for viremia, levels of SIVEnv-specific binding, and neutralizing antibodies. Virus-specific interferon ? and tumor necrosis factor ? cytokine responses to SIV-Nef, Gag, or Env peptide pools were measured in peripheral blood CD8 T cells. RESULTS:Macaques receiving ethanol had both higher plasma viremia and virus-specific cellular immune responses compared with the sucrose-treated group. The emergence of virus-specific cytokine responses temporally correlated with the decline in mean plasma viral load after 14 days postinfection in all SIV-infected animals. However, neither the breadth and specificity nor the magnitude of virus-specific CD8 T-cell responses correlated with early postpeak reductions in plasma viral loads. In fact, increased cytokine responses against Gag, gp120, and gp41 positively correlated with plasma viremia. Levels of SIV envelope-specific immunoglobulin G and neutralizing antibodies were similar over the disease course in both groups of macaques. CONCLUSIONS:Persistently higher antigen-specific cytokine responses in animals receiving ethanol are likely an effect of the higher viral loads and antigen persistence, rather than a cause of the increased viremia.

SUBMITTER: Pahar B 

PROVIDER: S-EPMC3812314 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature