Lab Research Focus
The focus of research in my laboratory is the class of T-lymphotropic retroviruses that induce AIDS in humans and various species of monkeys. Using both HIV-1 infection of chimpanzees, and SIV infection of macaques as model systems, we are attempting to understand the pathogenesis and natural history of HIV infection in humans at molecular and biologic levels. These studies involve in vitro and in vivo characterization of prototype and variant virus isolates and analysis of virus-host interactions that may influence disease progression. These interactions include the roles of cellular and humoral immune responses, different T-cell activation pathways, cell proliferation, and apoptosis. In addition to determining biologic properties, we are using PCR amplification and nucleotide sequencing of related viruses to identify viral determinants of pathogenesis at the molecular level.
Because many people are coinfected with HIV and HTLV (human T-cell lymphotropic virus), we have established a macaque model of SIV-STLV coinfection and are evaluating interactions of the two retroviruses in primary cells and in macaques. A second major area of investigation involves evaluation of vaccines, using both the HIV-chimpanzee and SIV-macaque models, and elucidation of those facets of virus-specific immunity that constitute protective immune responses. We have demonstrated that vaccination of chimpanzees with HIV antigens can elicit protection against intravenous infection with both cell-free and cell-associated HIV. Currently, we are using chimpanzees chronically infected with different HIV-1 strains to study (1) broadening of HIV-1- specific immune responses after superinfection with a second HIV-1 strain, and (2) whether prior infection prevents establishment of high viral burdens upon infection with a more pathogenic strain. In the SIV-macaque model, we are testing novel recombinant poliovirus vectors expressing SIV and HIV antigens in combination with other immunogens for potential use as a vaccine.
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