Alcohol abuse is a highly prevalent comorbid condition in the HIV-infected population, which increases the risk of HIV transmission and adversely affects disease progression. Using Simian Immunodeficiency Virus (SIV) infected rhesus macaques exposed to chronic binge alcohol (CBA), our studies have shown that CBA alters multiple aspects of SIV infection and disease by increasing CD4+ target cell proportions in the GALT prior to SIV, increasing susceptibility to rectal mucosal SIV challenge, increasing set point viremia, and decreasing median time to death. Our current studies sought to provide insights into virus:host interactions that affect early replication dynamics and influence disease progression in CBA animals.
We characterized the founder virus populations (FV) and replication kinetics in 14 CBA and 12 control rhesus macaques inoculated rectally with SIVmac251. FV were assessed using classic single genome amplification of SIV-gp160 and a novel next generation sequencing assay targeting V1-V2.
The numbers FV genotypes transmitted to individual animals did not differ between CBA and controls, with 1-3 genotypes observed (mean of 1.67, 1.86 respectively). However, genotypic analyses of FV populations showed that CBA animals expressed a more diverse founder virus population as compared to controls (p<0.001). At viral set point (10 weeks p.i.), CBA-treated animals showed significantly higher levels of viral RNA in both plasma and lymph node reservoirs (p<0.05), while similar lymph node proviral DNA burdens were observed CBA and control animals. Further analysis at set point of intra-animal evolutionary changes in viral genotypes showed that control animals exhibited a minor increase in diversity, while CBA animals showed a significant reduction in diversity (p<0.001).
These observations suggest that CBA mitigates early host selective pressures resulting in the establishment of a more genetically diverse founder viral population. At set point, increased viral RNA levels in tissue reservoirs and higher plasma viremia in CBA animals, concomitant with a decrease in diversity of expressed viral genotypes.