Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

More than 70% of the current 33 million people living with HIV-1 are young women, aged 15-24 years, who have acquired the virus through heterosexual contact. The risk of infection is significantly influenced by factors that are naturally present within the cervix/vagina. A group of Highly Exposed Sero-negative (HESN) women, within a sex worker cohort in Nairobi, demonstrate apparent resistance to HIV. This group of women have shown numerous differences in their immune responses and protein production in cervical secretions compared to women who are susceptible to infection. One group of proteins that have been shown to be significantly up-regulated in these HESN women are antiproteases, specifically members of the serpin family (B1). Serpins are a group of serine protease inhibitors and have known anti-inflammatory activity in numerous cell types, including the primary target cells for HIV-1. Specific serpins have also been shown to directly inhibit HIV-1 infection. The ability of antiproteases to reduce inflammatory levels and directly interfere with the infectivity of HIV-1 may, in part, be responsible or the protective phenotype exhibited in HESN women against HIV-1 infection. Preliminary experiments have demonstrated that HIV-1 anti-viral activity by Serpin B1. This study will seek to determine how serpin B1 affects the immune cascade, inflammation in target cells as well as its ability to interfere with the ability of HIV to infection various primary cells and cell lines. We will employ the use of semen and whole cervicovaginal lavage in select experiments in an effort to create an environment closely resembling that of heterosexual intercourse. This work has the potential to identify effective candidates for the development of novel microbicides against HIV-1, providing female-controlled protection options.