Grant: CIHR Fellowship

More than 34 millions of people are infected with HIV-1 worldwide and over 25 millions have already died of AIDS. In 2011, about 71300 Canadians were living with HIV/AIDS, including 25% that were unaware of their infection. AIDS patients show high variability in the speed of progression towards the disease stages of HIV-1 infection in the absence of treatment. A Montreal-based cohort of AIDS patients relatively resistant to disease progression has been assembled over the years: the slow progressors cohort that includes the elite controllers that maintain very low to undetectable viral replication. While some immunological features have been shown to correlate with accelerated or slowed progression in certain cases, HIV-1 inhibition is not fully explained in the majority of slow progressors. We hypothesize that in these patients, the pressure exerted by T cells immune response lead to mutations in HIV-1 capsid protein, which in turn, makes the virus more sensitive to inhibition by TRIM5alpha, a protein that can efficiently disrupt incoming retroviruses. To test this hypothesis, for each given subject, we will conduct various analyses to quantify the capacity of TRIM5alpha to inhibit the replication of the major HIV-1 strain infecting this patient. These analyses will be coupled with an examination of other immune correlates of HIV-1 control (such as the T cells response), as well as TRIM5alpha genotyping. Altogether, the experiments proposed here will allow us to address extensively the role of TRIM5alpha and its complementarity with the T cell response in restricting the progression to AIDS in humans. The results of this study will represent a major incentive to develop new therapeutic tools to enhance HIV-1 targeting by TRIM5alpha in normal progressors AIDS patients.