Lessons on Non-Progression of HIV Disease from Monkeys

SIV challenge in monkeys immunized with SIV DNA delivered by employing rhesus CMV and Adenoviral vectors correlated with high frequencies of virus-specific effector memory CD4+ T cell responses within the potential sites of SIV replication (Hansen et al., 2011). In our lab, studies testing peptide-based vaccine (Nehete et al., 1998, 2001, 2005, 2008) and adenovirus vectored vaccines (Mercier et al., 2007; Weaver et al., 2009) against systemic or mucosal challenge with different strains of simian human immunodeficiency viruses (SHIV ku2, SHIV89p, and SHIV 162p3), revealed strong correlation for virus control, to undetectable levels in significant population of animals, preferentially with antigen specific cellular immune responses (CD4+ and CD8+ T cells). We also assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model and observed that functional impairment of CD4+ T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA + I stimulation (He et al., 2011). Two other immune cell types recognized for potential contributions to influence virus control in SIV infected rhesus macaques and HIV-infected humans include CD4+ T cells subsets that either produce IL-17, Th17 cells, or exert immunosuppressive function, CD25+FoxP3+ regulatory T cells or T-reg (Cecchinato and Franchini, 2010). Depletion of Th17 cells in humans as well as macaques, relatively soon after virus exposure, has been associated with the dissemination of microbial products from the infected gut, thereby adding to the systemic immune activation and disease progression. On the other hand, T-regs Lessons on non-progression of HIV disease from monkeys