Of all in vivo sources of virus, plasma virus can be obtained in quantities high enough that it can be directly studied and much important information has previously been gained by its study. However, little is known regarding the in vivo mechanism(s) of its clearance and destruction. Defining what immune mechanisms are effective in vivo and their mode of action are important for understanding various aspects of HIV biology and designing vaccines and therapies. Recently, the investigators obtained evidence that strongly suggests that complement and antibody together are playing an important role in clearance and destruction of plasma virus. The overall goal of this proposal is to define this mechanism by providing critical information in several important areas. They will determine the class of molecules and the specificity of the molecules that react with virus in vivo and lead to complement activation. They will determine the effect of this possible clearance mechanism on infectious and noninfectious plasma virus from different phases of disease, including acute infection and later stages. Differences between plasma virus and primary isolates will be assessed and the underlying causes of the differences determined. The role of this mechanism in the SIV/macaque model of HIV disease will also be determined by in vitro and in vivo studies. Much of the information gained from this proposal will be of special interest, since it will be obtained by evaluating an in vivo source of virus that is unselected by culture. The methods, which include complement-mediated lysis of, and immunoprecipitation of plasma virus, will serve as unique and sensitive assay systems. These studies will thus provide a unique view of the interaction of HIV with the immune system. These studies, by enabling a better understanding of the interaction of HIV-1 with the immune system, will lead to a better understanding of how the immune system can be manipulated to enhance anti-viral immunity.
