Genetic correlates of HIV resistance
Marlin, Crystal Lynn
The Human Immunodeficiency Virus 1 (HIV-1) epidemic continues to claim millions of lives, despite intense research and public health programs. A natural model of resistance is crucial for the development of an effective vaccine. We have identified a group of sex workers in Nairobi, Kenya, who appear to be resistant to infection with HIV. Research on this cohort has identified numerous immunological and genetic correlates to HIV resistance, but has failed to completely explain the phenomenon. Genetic studies have shown that HIV resistance occurs in families, with both sex worker and non-sex worker relatives of HIV resistant women less likely to be HIV infected. In addition, HIV resistance has been associated with altered innate immune responses, as measured by cytokine production to toll-like receptor stimuli. To test the hypothesis that there is a genetic component to HIV resistance, we will address two specific objectives within this thesis: 1) identify known polymorphisms associated with HIV resistance in the kindred of these women; more specifically interferon regulatory factor 1 (IRF-1) polymorphisms, and 2) identify polymorphisms within toll-like receptors (TLRs) that may be responsible for the altered and apparently successful immune responses in HIV resistant women. Our findings show an association between HIV resistant kindred and an IRF-1 microsatellite, as well as, with an IRF-1 single nucleotide polymorphism. No associations were found between HIV resistance and the investigated TLR2 and TLR4 polymorphisms. These results also suggest a genetic component to HIV resistance, but do not fully explain the altered immune responses observed within these women.