Identifying the sequence of transmitted strains during acute infection, and defining viral sequence evolution in relation to immune selection pressure, represent critical issues to the development of a successful HIV vaccine. As such, the HIV Sequencing Core will be responsible for the generation of thousands of viral sequences that will require a concerted, organized, and high-throughput approach. To this end we have merged the experience of the Partners AIDS Research Center (PARC) Sequencing Core with the expertise of the Broad Institute (Broad) at the Massachusetts Institute of Technology and Harvard. PARC will manage the collection of samples, isolation of HIV DNA/RNA and initial PCR amplification. Products will then be provided to the Broad for further amplification, sequencing, and data assembly and analysis. Thus, the HIV Sequencing Core is designed to perform full genome viral sequencing on all subjects with primary HIV-1 infection enrolled in this proposal. These data will provide the baseline virology data to select individual study subjects for the proposed specific studies on immunodominance, viral escape, viral fitness, antigen processing, T cell function and T cell receptor usage. Specifically, the HIV Sequencing Core will generate full viral genome sequences at baseline from each of the 600 study subjects, including previously enrolled acute and early infected subjects as well as newly identified acute and early infected subjects. We will also provide follow-up viral sequencing on 150 acute or early untreated subjects at 2, 6, and 12 months of infection. These data will provide a comprehensive analysis of the sequence of transmitted strains as well as viral evolution during untreated HIV infection to enable identifying the rate of viral evolution and specific sites under selection pressure. The Sequencing Core will be responsible for: 1. Characterization of full genome viral sequences at baseline from all 600 acute and early infected subjects and longitudinal time points (2, 6,12 months) post infection in 150 untreated subjects. 2. Automated assembly of sequence data and Inclusion of these data into a database that will enable identification of study subjects for the specific research projects proposed.
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