The Overbaugh lab, led by Julie Overbaugh, has a long-standing interest in understanding the mechanisms of HIV-1 transmission and pathogenesis. The lab is part of a larger team, comprising researchers in both Seattle and Kenya (The Kenya Research Program). Trainees in the lab have opportunities to engage in studies of viral evolution, virus-host cell interactions, and viral immunology all within the context of international collaboration.
Previously, the lab has shown that there is a genetic bottleneck in the viruses that are transmitted between heterosexual partners, leading to selection of just one or a few HIV variants in the new host. Members of the lab have also found similar evidence of a bottleneck in the context of mother-infant transmission, where the infant is infected in the presence of maternal HIV-specific antibodies. Current work aims to reveal how the transmitted variants "escape" from maternal immune pressure and elucidate whether functional characteristics of maternal antibodies from the blood and breast milk compartments are associated with risk of transmission.
Another main focus of the lab is on HIV-1 superinfection, an occurrence where people already infected with HIV become re-infected with HIV from a different source partner. The lab has shown that superinfection is common in high-risk groups although the risk of superinfection is lower than the risk of initial HIV infection, suggesting there may be some protection afforded by the initial HIV immune response (Ronen et al., PLoS Pathogens, 2013). Ongoing efforts are focused on whether there is any immune response from a first HIV infection that provides protection against reinfection. An additional avenue of research in the lab aims to characterize the kinetics and epitope targets of the broad antibody response that developed post-superinfection in a subset of “elite neutralizers”. The study of these individuals is aimed at understanding the mechanisms that lead to a broad antibody response.
Other studies in the lab are focused on identifying virus strains that effectively represent those spreading in high-risk populations. These viruses are being used to measure immune correlates and to develop models for studying HIV transmission for assessing vaccine and prevention approaches. Ongoing studies are focused on defining the virus-host interactions that limit replication of these circulating HIV variants in non-human primate cells.
In partnership with clinicians within the Kenya Research Program, the lab is also studying antiviral drug resistance, with emphasis on resistance that develops in the setting of prevention of mother-to-child transmission and in adults who use antiretroviral drugs for prophylaxis. Another major effort of these studies is developing HIV assays to detect diverse HIV variants circulating in Africa.