The role of Trappin-2 and RANTES in mediating resistance to HIV-1 infection

Abstract

There are currently more than 33 million people worldwide who are infected with HIV-1 despite development of novel treatments and knowledge of prevention strategies. Within the Pumwani area of Nairobi, Kenya there is a group of commercial sex workers who are highly exposed to HIV-1. A small subset of these women have been classified as resistant to HIV-1 infection as they remain HIV un-infected despite as many as 60 unprotected sexual exposures to HIV each year. A better understanding of such a natural model of HIV resistance would be invaluable to inform the development of a protective HIV vaccine or microbicide. Globally, heterosexual transmission of HIV across mucosal surfaces is responsible for the bulk of new infections and thus it is important to examine both the macro and the micro environments of the vaginal mucosa in efforts to determine what enhances and what thwarts HIV-infection. Previous studies have shown elevated levels of RANTES, a natural ligand for the dominant HIV co-receptor CCR5, in cervicovaginal secretions of HIV-resistant women. Additionally, a novel HIV-inhibitor, Trappin-2 was previously shown to be elevated in cervicovaginal secretions of HIV-resistant women. To test the hypothesis that RANTES and Trappin-2 in cervicovaginal fluid are important mediators of HIV resistance we will: 1) measure RANTES in a much larger group of women from the Pumwani cohort, and 2) measure Trappin-2 levels in samples taken at different time points, and 3) correlate Trappin-2 levels in cervicovaginal fluid with biological confounding variables, and 4) investigate whether SDF-1 plays a role in HIV-disease progression in HIV-positive women.