Manipulation of SIV pathogenesis
Non-human primates are the best animal model to study the pathogenesis of HIV. The two common models for SIV pathogenesis are pathogenic and non-pathogenic SIV infections. The most widely used model of pathogenic infections is Rhesus macaques (Rh) infected with SIV strains derived from sooty mangabeys. Disease progression to AIDS occurs within a period of months to years, depending upon the SIV strain used. The best known example of non-pathogenic infections is African NHPs naturally infected with SIV. These animals rarely progress to AIDS despite maintaining levels of viremia that are at the same levels or higher than SIV viral loads in pathogenic infections. Little is known about the components of the immune system that are important for controlling SIV replication and disease progression in NHPs and HIV-infected humans. By understanding which immune correlates are important for controlling virus replication and progression to AIDS, it will be possible to design new HIV treatments. We intend to modulate SIV pathogenesis by separately depleting CD20, CD8, and regulatory-T cells in pathogenic and natural SIV infections of Rh and AGMs. Depletion of these cell types revealed that CD8 cells have a greater impact on SIV replication than depletion of CD20 cells. Moreover, we found that the experimental induction of immune activation, resulted in increases in viral replication, indicating that both immune activation and CD8+ cells are important controllers of disease progression to AIDS. These findings will be useful in the design of new therapies and treatments for HIV patients