Chronic Alcohol Consumption Results in Higher Simian Immunodeficiency Virus Replication in Mucosally Inoculated Rhesus Macaques

Abstract

The influence of alcohol consumption on HIV pathogenesis is not well understood. In this study we used the SIV/macaque model of HIV infection to study the influence of chronic binge alcohol consumption on simian immunodeficiency virus (SIV) infection. Rhesus macaques were fed alcohol or isocaloric amounts of sucrose via indwelling intragastric catheters and then inoculated with SIVmac251 by the rectal route. Real-time RTPCR for SIV gag mRNA showed significantly higher plasma viral copies in alcohol-consuming macaques at 4 and 6 weeks pi, compared with sucrose controls. The viral copies were 1 to 2 logs higher in these animals. The percentage of CD8+ lymphocytes in the duodenum of alcohol-consuming macaques was significantly lower than in sucrose-consuming macaques both before infection as well as at different time points postinfection. Also, the percentage of CD4+CD3+ lymphocytes in the intestines was significantly higher in alcohol-consuming macaques before infection. These findings suggest that a higher percentage of SIV target cells (CD4) in the gut coupled with lower percentages of CD8 cells, which could be important in controlling virus replication, may be responsible for the higher SIV loads observed in alcohol-consuming macaques.

Moderate alcohol consumption enhances vaccine-induced responses in rhesus macaques

“…Overall, chronic ethanol selfadministration did not modulate the frequency or subset distribution of circulating lymphocytes. This observation is consistent with some reports of chronic ethanol exposure in rodents, NHPs and humans [8,34,35]. Nonetheless, other studies have reported significant perturbations of both the number and frequency of peripheral T and B cells with either acute or chronic alcohol exposure (reviewed by [34,36]).…”

“…As previously described in humans and animal models [1,2,4,6,8,[37][38][39][40], our results indicate heavy chronic ethanol consumption impairs several key aspects of vaccine-elicited immune responses including T and B cell proliferation, T cell cytokine production and antibody secretion. Importantly our data suggest that recall responses to vaccines received prior to alcohol consumption might also be compromised.…”

“…Ethanol also inhibits allogeneic T cell responses (reviewed in [7]). Finally, in rhesus macaques, multiple studies have demonstrated ethanol consumption significantly inhibits the control of Simian Immunodeficiency virus replication [8][9][10]. However, no study to date has compared the effects associated with chronically drinking intoxicating versus moderate amounts of ethanol as defined by a BEC cut off of 80 mg/dl [11].…”

CD4 T Cell Depletion at the Cervix during HIV Infection Is Associated with Accumulation of Terminally Differentiated T Cells

“…This finding may reflect that, in the absence of HIV infection, TD T cells may be slowly lost through activation-induced death in the presence of genital inflammation, while CD45RA Ϫ CCR7 ϩ CM T cells are recruited to replenish the diminishing CD4 T cell pool. Although CD45RA Ϫ CCR7 ϩ CM T cells are not common at mucosal sites and their identification was surprising, CM cells that were identified in the mucosal effector sites in macaques have been proposed to be "reserve" antigen-experienced cells that are in a "quasiresting" state awaiting another exposure to the antigen of original stim- (38). Despite evidence that inflammatory cytokines may alter the differentiation status of T cells in an antigenindependent manner (12,42), the association between inflammatory cytokines in genital secretions and differentiation of individual T cell subsets isolated from the cervix was not evident in HIV-infected women in this study.…”

Behavioral, Metabolic, and Immune Consequences of Chronic Alcohol or Cannabinoids on HIV/AIDs: Studies in the Non-Human Primate SIV Model

“…The higher viral load and accelerated disease progression occured despite CBA-administered animals having greater virus-specific cellular immune responses and similar humoral responses compared to a sucrose-treated group (Pahar et al 2013). A possible mechanism for the enhanced viral replication may be alcohol-mediated alterations in the gut mucosal immune system, as there were higher percentages of central memory and naïve CD4+ T cells in duodenal tissues of CBA macaques prior to SIV inoculation (Poonia et al 2006a). After infection, CBA animals had higher levels of SIV in the gut mucosa sampled at viral set point (approximately 10 weeks post-inoculation) (Poonia et al 2006b).…”