Viral-immune Interaction in Hiv Infection: Cohort Studies in Macaques Infected with Cxcr4 and Ccr5 Tropic Immunodeficiency Viruses

HIV epidemic has caused a health crisis globally. We have analyzed and modeled data from animal models of HIV, HSV and influenza virus, aiming to understand the role of neutralizing antibodies (nAbs), CD4+ T cells, CTLs and APCs in HIV infection. Our analysis demonstrates that passive antibodies confer protection against macaque SHIV89.6P by either neutralizing the initial viral inoculums or reducing the acute viral growth. Therefore, vaccines that elicit high nAb levels during early infection may induce sterilizing immunity or delay disease progression. We further show a positive correlation between peak viral level and the acute CD4+ T cell depletion in SHIV89.6P infection, which implies that reduction of peak viral level significantly preserves CD4+ T cells. Further study on influenza and HSV-1 infections suggests that antigen loading rate of APC determines the magnitude of antigen presentation and the APC decay is mainly due to the degradation of pMHC, not CTL killing. The slow kinetics of HIV viral growth may be one factor that limits the level of antigen presentation and subsequent CTL response. This book should be helpful for virologists, epidemiologists and HIV researchers.