We have identified sets of analogous MHC molecules in humans and rhesus macaques. We now propose to expand these analyses to include a cohort of Chinese rhesus macaques infected with Simian Immunodeficiency Virus (SIV). These animals represent a unique model of AIDS infection in that a subset of the infected animals displays characteristics of long-term non-progressors (LTNP), similar to HIV-infected humans. We propose to assess whether these animals express alleles which influence disease progression, similar to HIV- infected humans. It has yet to be determined the mechanism by which these alleles alter disease course. If we can characterize a non-human macaque model which mimics the HLA effect in human HIV infection, we may be able to gain some insight into these phenomena. We will also determine the T-cell activation profiles of these SIV-infected macaques, which in humans has also been shown to have an affect on the ability to progress or hinder the development of AIDS. Accordingly, we propose the following specific aims:
Specific Aim 1. To determine whether functionally analogous MHC molecules exist in the context of SIV infection of Chinese rhesus macaques We will test cryopreserved or fresh peripheral blood mononuclear cells for human responses against MHC molecules which have been shown to have an impact on the progression to AIDS. The animals which have responses against these epitopes will have their MHC alleles sequences and characterized further for their potential to serve as analogous MHC molecules.
Specific Aim 2. To identify the T-cell activation profile of these macaques using intracellular antibodies. The phosphorylation status is generally a signature of the activation level or status of the protein. Understanding how those cascades are affected by SIV infection, comparing the effect of human HIV-1-infected- versus macaque-SIV-infected cells, and more importantly for the aim of this grant, comparing cells from LTNPs, short-term progressors and normal cells, can reveal important steps in progression or/and susceptibility to disease. These studies will provide the first insight into why some animals progress to AIDS more rapidly than others, similar to HIV-infected humans. Information obtained from this model will allow for the development of interventions which may affect the progression to AIDS in humans. Project Narrative We propose to study a group of non-human primates, rhesus macaques, which have been infected with Simian Immunodeficiency Virus (SIV). These animals represent a unique model of AIDS infection in that a subset of the infected animals displays characteristics of long- term non-progressors (LTNP), similar to HIV-infected humans. We propose to assess whether these animals express immune markers which influence disease progression. ? ? ? ?
