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Effects of Alcohol Consumption on Antigen-Specific Cellular and Humoral Immune Responses to SIV in Rhesus Macaques

Pahar, Bapi DVM, PhD*; Amedee, Angela M. PhD; Thomas, Jessica MD, PhD; Dufour, Jason P. DVM*; Zhang, Ping MD, PhD‡,§; Nelson, Steve MD; Veazey, Ronald S. DVM, PhD*; Bagby, Gregory J. PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 December 2013 - Volume 64 - Issue 4 - p 332–341
doi: 10.1097/QAI.0b013e31829f6dca
Basic and Translational Science

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 γ and tumor necrosis factor α 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.

*Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA;

Departments of Physiology;

Medicine, Louisiana State University Health Sciences Center, New Orleans, LA; and

§Department of Surgery, Michigan State University College of Human Medicine, East Lansing, MI.

Correspondence to: Bapi Pahar, DVM, PhD, Division of Comparative Pathology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433 (e-mail: bpahar@tulane.edu).

B.P. and A.M.A. contributed equally.

The authors have no conflicts of interest to disclose.

Supported by National Institutes of Health grants AA009803, AA007577, and AA007555, the National Center for Research Resources, and the Office of Research Infrastructure Programs of the National Institutes of Health through grant no. OD011104-51.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received January 15, 2013

Accepted June 03, 2013

© 2013 by Lippincott Williams & Wilkins