Project 3. A hallmark of HIVs success is rooted in extreme sequence variability, and recent deep sequencing efforts are increasing the amount of available data dramatically^^?. 28) Most previous sequence analysis focused on gpi20 sequences due to its direct interaction with the host immune system. While HFV sequences diverge, they do so under evolutionary pressures, and sequences are, therefore, a formidable source of information to identify the role that individual amino acids play in functional properties. HIV sequence variability impacts not only envelope but all HIV proteins, and we propose to focus on CA. The major evolutionary constraints on CA are associated with its structural integrity, its dynamic properties during assembly and disassembly, and its interaction sites with host proteins. We plan to exploit HIV and SIV sequence data to carry out an analysis of CA protein sequence variability and explore its impact on capsid structure, dynamics, and function.
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