The etiologic agent for acquired immunodeficiency syndrome (AIDS) is a retrovirus termed human immunodeficiency virus (HIV). While much is known of the biochemical and molecular properties of virus expression, the pathogenic mechanisms involved in the clinical progression of disease in HIV infected people is only poorly understood. A non-human primate model is thus critical to the understanding of the in vivo events culminating in AIDS. Simian T-lymphotropic virus type III (STLV-3) is a retrovirus originally isolated from macaques with signs of AIDS like disorders. This virus is closely related to HIV in genomic structure, in vitro growth characteristics, and in its capacity to cause AIDS in its host. It is also clear that African Green monkeys represent the natural reservoir for STLV-3 and show no signs of pathology related to infection. By comparing the clinical course of infection in experimentally infected AGMs and macaques, the underlying host factors responsible for protection in one species and death in the other can be studied. Specifically, comparison of virus expression and tissue localization in these hosts and the temporal relationship to disease state may provide clues to the pathogenesis of STLV-3 infection. Genetic factors related to immune response genes may play a crucial role in resistance to disease in AGMs. The ability of the host to protect itself from the devastating effects of T cell depletion are theorized to be a result of effective immune regulators which maintain the virus in a latent state. Thus continued reactivation of virus expression seen in HIV infected people may be circumvented in AGMs due to an effective humoral and/or cell-mediated response. Antibody responses to antigenic determinants of gp120 of HIV function in neutralization and the prevention of receptor binding to the T4 receptor on lymphocytes and monocytes. Therefore, antibodies from naturally infected AGMs will be analyzed for recognition of synthetic peptides to predicted antigenic determinants of gp120 and gp32 of STLV-3 and compared with inoculated AGMs and macaques. In addition, antibodies reactive to these peptides will be examined for virus neutralization so that protective epitopes can be defined. The results of this project should help in understanding the complex interactions of host responses to retroviral pathogenesis.
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| Allan, J S; Kanda, P; Kennedy, R C et al. (1990) Isolation and characterization of simian immunodeficiency viruses from two subspecies of African green monkeys. AIDS Res Hum Retroviruses 6:275-85 |
