The overall goal of this study is to define the virological and immunological properties of HIV-1 variants that are transmitted to and persist in women following mucosal infection. Worldwide, HIV-1 is predominantly a heterosexually acquired virus, but very little is known about HIV-1 variants that are transmitted to the mucosa, particularly in women. Yet, for a HIV vaccine to be effective, it will be essential that it protect against the virus variants that are most frequently transmitted The PAVE cohorts, which have been established to identify and monitor high risk HIV-1 negative individuals in preparation for HIV vaccine efficacy trials, provide an excellent population for studying early infection because a change in serostatus is detected within a one-two month period. In this study, we propose to analyze the virological and immunological responses in a PAVE cohort of female commercial sex workers in Mombasa, Kenya, where transmission occurs through mucosal exposure. This cohort also provides an opportunity for temporal studies of newly infected individuals, allowing analyses of the interplay of the specific virus, viral tropism and the immune response in defining the viruses that persist in the host.
The specific AIMs i nclude: 1: To define the envelope genotype of virus variants that are transmitted. To compare the envelope sequences of viruses in the mucosa to those in the blood at early times post- infection. To analyze the dynamics of the virus population over time in blood and the mucosa; 2: To determine the phenotype of viruses that are present in the cervix and blood at early times post-infection; 3: To define early immune responses to autologous virus and to determine the potential role of cellular and humoral immune response in affecting selection for certain variants in blood and mucosa. To determine the potential role of cellular and humoral immune response in affecting selection for certain variants in blood and mucosa; 4: To define the early target cells for infection in the mucosa and determine if the types of cells infected in the host correlate with the cell culture-defined properties of the viruses.
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