Simian immunodeficiency virus (SIV) infection of macaques is an excellent model for studying AIDS. Sequence similarities to HIV and the ability to induce AIDS in macaques make SIVs and their infection of these monkeys particularly important models for understanding the immune response to the AIDS virus. They will utilize the SIV/macaque model to determine whether the generation of AIDS virus-specific CTLs can be protective against or can alter the course of AIDS virus infection in vivo. Furthermore, they will determine whether the MHC of the rhesus macaque can play a role in resistance to SIV infection. CTLs are critical for containment of viral disease progression in HIV-infected individuals. CTLs are important during the later courses of individuals infected with HIV and the rapid decline in CTL activity often presages the terminal disease stage. CTLs may also provide protection against infection. It has recently been shown that vaccination with a vaccinia construct expressing the SIV nef gene was sufficient to protect a cynomolgus monkey from SIV infection. High levels of CTL activity were correlated with ability to delay viremia in an additional two animals in this study. These observations provide the rationale to determine whether pre-existing CTLs can either prevent infection or modulate the course of disease post-infection. Although strong evidence exists for the important role of CTLs in HIV infection, it has been difficult to carry out definitive in vivo experiments. At the Wisconsin Regional Primate Research Center, they have recently defined 10 MHC-identical sibling pairs of rhesus monkeys for these kinds of experiments and have also initiated a breeding program to generate MHC-identical rhesus monkeys. They will, therefore, test the hypothesis that CTLs can protect individuals from AIDS-virus infection, and that CTLs can modulate the course of virus infection. They will use MHC-identical sibling pairs to test this hypothesis. Since the products of MHC genes bind pathogen-derived peptides and present them to T cells it has been suggested that these highly polymorphic molecules might influence he fashion in which an individual makes a response to the AIDS virus. Recent studies have indicated that certain HLA molecules may play an important role in long-term non-progressors. The investigators will also test the hypothesis that certain MHC haplotypes or MHC molecules can influence the course of SIV in vivo using sequence-based typing of rhesus macaque MHC class I and II alleles.
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