Professor of Immunology and Infectious Diseases
In 1985, we provided the first evidence of a retrovirus in West African people more closely related to Simian Immunodeficiency Virus (SIV) than to HIV-1 the prototype AIDS virus. Human Immunodeficiency Virus type 2 (HIV-2) as this virus is now called, shares many virologic properties with HIV-1, including cell tropism, antigenic and genetic similarities and genome organization. Our epidemiologic studies of both viruses in Africa, indicate a curious geographic distribution of these two related viruses. HIV-2 appears at high rates in West Africa, where the HIV-1 epidemic is now spreading.
Despite early fears that HIV-2 would create a second AIDS pandemic, current information suggests that HIV-2 and HIV-1 may have distinct biologic properties in people. It is therefore relevant to assess these differences in populations infected with significant rates of both HIV-2 and HIV-1. Senegal is a country with such populations and the collaboration we have had for the past 15 years provides a strong base for continued research.
We are involved in a number of prospective studies of HIV-2 and HIV-1 infected people in Senegal. By following healthy HIV positive individuals over time, we have found that the rate of AIDS development is >10 fold higher in HIV-1 infected individuals compared to HIV-2. We have found that HIV-2 is less transmissible compared to HIV-1, by both perinatal and heterosexual routes. Thus, HIV-2 appears to be a less virulent HIV virus, and we addressed the hypothesis that it might provide protection from subsequent HIV-1 infection. Our epidemiologic study showed that this appears to be the case, with close to 70% protection conferred by HIV-2 infection. Recent in vitro studies, suggest that beta chemokines may be mediators of the observed HIV-1 resistance.
Laboratory studies seek to explore viral mechanisms for the differences in observed biology between HIV-2 and HIV-1. Inter- and intra-patient variation in the nucleotide sequence of the envelope gene is thought to play a role in the pathogenesis of HIV-1. Overall intra-patient variation in HIV-2 appears to be less than that of HIV-1 and variation does correlate with clinical evidence of immunosuppression or overt disease. Similarly, we have utilized quantitative PCR to determine proviral and viral titers of sequentially evaluated HIV infected individuals. HIV-2 proviral load is similar to that of HIV-1 but plasma viral titers are at least 30 fold lower suggesting quiescent infection. Further studies seek to identify the viral or host factors critical for virus containment.
S.D., 1985, Harvard School of Public Health
D.V.M., 1982, University of Minnesota School of Veterinary Medicine