Grant: Operating Grant

Most HIV infections are acquired through heterosexual intercourse, and each year the rate of HIV-infected women increases dramatically. Initial exposure to HIV-1 during sexual transmission occurs in the genital tract, however, little is known about HIV-1-specific immune responses at this site. During the previous CIHR mandate (2006-2009), we established an ongoing cohort of heavily HIV-exposed commercial sex workers (CSWs), in Cotonou (Benin), in which we have identified individuals who remain HIV-uninfected (resistant) after more than 3 years of active prostitution. The fact that some individuals remain persistently seronegative despite high exposure to the virus such as the HIV-1-uninfected CSWs presented herein, implies that there are host factors that are highly protective. Interestingly, we have recently demonstrated distinct mucosal inflammatory patterns associated with either susceptibility or resistance to infection. In the current study, we propose to investigate the role of the genital cellular populations and cytokine/chemokine genetic polymorphisms on the modulation of the mucosal inflammatory patterns associated with either susceptibility or resistance to HIV infection. This study will identify key host factors associated with HIV infection and will provide novel insights on their role in modulating the genital mucosal immune response towards HIV.