Dr. Swanstrom’s lab focuses on HIV-1 sequence evolution from transmission to pathogenesis. He and his team try to link viral sequence changes to changes in viral phenotypes or changes in virus-host interactions.
Immunosuppression as the result of infection with HIV-1 is fatal and is associated with the appearance of opportunistic infections and cancers that include EBV-driven lymphomas and HHV-8-driven Kaposi’s sarcoma. Successful suppressive therapy of HIV-1 infection has been achieved with the Swanstrom graphicintroduction of inhibitors directed at the HIV-1 protease. Therapy failure is associated with the development of drug resistance. A major effort is directed at understanding the role of the protease and proteolytic processing in the virus life cycle, and assessing the nature of drug resistance to protease inhibitors. Dr. Swanstrom and his team are especially interested in defining the extent to which drug resistance mutations compromise the fitness of the drug-resistant virus. A second area of research has to do with the role of the HIV-1 Env protein in pathogenesis and its use in vaccine development. Evolution within the env gene can result in a more pathogenic version of HIV-1 that leads to accelerated disease course. These studies have led to a more general consideration of the nature of selective pressure on the viral envelope protein and the mechanisms at work generating diversity in the viral genome as a result of that selective pressure. Finally, in a collaborative effort with Dr. Robert Johnston and Dr. Nancy Davis, we have been involved in the use of an alphavirus vector to deliver HIV-1 sequences in a vaccine strategy.