HIV infection leads to a variable clinical latent phase until the appearance of disease; some patients progress to AIDS in less than 2 years, while others are asymptomatic after more than 10 years of infection. It is likely that variation of HIV itself is largely responsible for these differences in clinical course, and we propose to characterize HIV isolates from long-term asymptomatics in a cohort of Argentinean hemophiliacs who were infected by HIV-contaminated clotting factors in 1983-84. We propose to characterize the biologic properties of HIV-1 isolated from these individuals, amplify and sequence HIV-1 genes that may contribute to biologic variation, and assess the pathogenicity of HIV-1 isolates from asymptomatics in the human PBL-SCID model. This collaborative project involves the laboratory of Dr. Donald Mosier at The Scripps Research Institute in La Jolla and Dr. Gaston Picchio, director of the Laboratory of Virology, Institute for Hematologic Investigation, National Academy of Medicine, in Buenos Aires, Argentina. Isolation of virus and biologic characterization will take place in Buenos Aires, and molecular characterization of virus and hu-PBL-SClD experiments will be done in La Jolla. Preliminary experiments in Buenos Aires have characterized the biologic properties of isolates from long- term asymptomatics, and the nef gene from 5 of these isolates has been cloned and sequenced in La Jolla. We plan to extend these studies to more virus isolates, with the additional sequencing of env, tat, and LTR regions, and to characterize virus isolates for their ability to replicate and cause CD4 T cell depletion after infection of hu-PBL-SClD mice.
