DEVELOPMENT OF A MONKEY MODEL FOR TESTING OF ANTIVIRAL AGENTS AGAINST HIV-1

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The human immunodeficiency virus (HIV-1) causes AIDS in man. The development of an animal model system for infection and disease by HIV-1 is essential for AIDS vaccine studies and intervention. Currently, the only animal species which can be infected by HIV-1 is the chimpanzee; however, n disease is produced. Due to the enormous cost of maintaining a chimpanzee and the fact that this cannot be a disease model, a better model was sought Based upon a report from the Washington Primate Research Center, studies were undertaken to investigate HIV-1 infection in pig-tail monkeys. Four monkeys have been inoculated with two isolates of HIV-1 which differ in their env regions: two monkeys received LAV, which is similar in its env to the laboratory adapted strain, HIV-1 IIIB; and two monkeys received a primary isolate (<4 passages) which is similar in its env region to the MN strain, which represents the majority of North American HIV-1 isolates. Th monkeys will be analyzed for infectivity as follows using blood samples collected every two weeks post-inoculation: PBLs will be prepared for viru isolation; plasma will be obtained for antibody detection by Western blot analysis; DNAs will be prepared from PBLs for analysis of viral DNA by PCR; blood will be phenotyped for CD4 and CD8; serum chemistry also will be performed. Additionally, recombinant HIV-1 DNAs are being constructed to generate a virus with an increased tropism for monkey cells. Such a virus will also b tested in vivo for its potential use in developing the monkey system for studying HIV-1 induced AIDS.