In 1985, we provided the first evidence of a simian virus related in immunodeficient macaque monkey, later designated as Simian Immunodeficiency Virus. SIV has been an important animal model system for pathogenesis, vaccine and drug development for HIV/AIDS. We further described the natural host of SIV as African Cercopithecine primates. In 1985, we provided the first evidence of a SIV-related virus in humans in Senegal, West Africa. HIV-2 is the closest human immunodeficiency virus related to HIV-1.
The discovery of HIV-2 prompted fears of a second global AIDS pandemic, understanding the clinical significance of HIV-2 required studies in people. We collaborated with Professor Souleymane MBoup at Cheikh Anta Diop University in Dakar, Senegal to prospectively study HIV-2 and HIV-1 infection in a cohort of registered sex workers. The cohort was studied for over 25 years and represented one of the longest natural history studies of HIV worldwide, with the unique characteristics of high-risk women and persistent prevalence of HIV-1 and HIV-2.
HIV-2 is largely confined to West Africa, while HIV-1 infection is prevalent worldwide and accounts for over 98% of all HIV infections globally. Importantly, disease progression to AIDS occurs much more slowly in HIV-2. In comparison to HIV-1, these biologically relevant characteristics of HIV-2 infection in vivo appear to model those of an attenuated HIV infection. This allowed the description of a less virulent disease phenotype characterized by robust cellular and neutralizing immune responses, coupled with low viral carriage. The long term observation of both HIV types in a high risk population allowed the description of HIV-2 protection from incident HIV-1. A number of in vitro mechanisms for this protective mechanism were identified, including beta-chemokine secretion, which would block the required HIV co-receptor binding, lowered co-receptor expression coupled with a robust and cross-protective immune response. Our hypothesis was that distinct immunologic profiles of effective innate and acquired responses in HIV-2 infection provided important new information guiding our understanding of HIV pathogenesis and future vaccine design.