Presenter: Avani D. Shah

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Presenter: Avani D. Shah

Mentor: David Camerini

Title: Insights Into the Secondary Structure of Chemokine Receptor CCR5 and the Pathogenesis of HIV-1 Infection

AIDS has affected more than sixty million people worldwide. HIV-1 is a retrovirus that causes AIDS. To attach, fuse and then enter into the cell, HIV-1 binds to the cell surface glycoprotein CD4 and then to a chemokine receptor, such as CCR5. Numerous studies have shown that HIV-1 entry into cells is the rate-limiting step in viral replication. It has been shown that 50 percent of the time, HIV-1 entry is mediated exclusively by CD4 and CCR5. The importance of the chemokine receptor CCR5 in HIV-1 infection is illustrated by the fact that people who lack CCR5 are strongly protected from HIV-1 infection. Although the two-dimensional topology and amino acid sequence of CCR5 has been determined, we hope to find the secondary-spatial structure or a 3-D topology of the CCR5 protein. We are currently studying ways to prevent or limit the pathogenesis of AIDS caused by HIV-1 infection of CD4-positive cells, such as T cells and macrophages, via the chemokine receptor CCR5. We are also using a cell line that we created, which expresses very high levels of CCR5, in conjunction with Dr. Hartmut Lueke’s lab, to purify native CCR5 and eventually obtain a crystal structure of the CCR5 membrane protein.