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Title page for ETD etd-12042017-090452


Type of Document Dissertation
Author Burse, Mallori Jacole
URN etd-12042017-090452
Title Inhibitory Control of HIV-1 by Cyclophilin A
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Earl Ruley Committee Chair
Christopher Aiken Committee Member
David Cortez Committee Member
Kristen Ogden Committee Member
Keywords
  • restriction factors
  • virus-host Interactions
  • HIV-1
  • cyclophilin A
  • CypA
Date of Defense 2017-10-09
Availability restrictsix
Abstract

The host protein cyclophilin A (CypA) can both stimulate and inhibit HIV-1 infection through its interaction with the viral capsid (CA). CypA enhances the early stages of HIV-1 infection in part by promoting nuclear import of the virus; while the details of its ability to inhibit HIV-1 infection are less clear. This thesis advances our understanding of the mechanisms underlying the ability of CypA to inhibit HIV-1 infection. I demonstrate that CypA inhibits nuclear import of HIV-1 in the presence of inhibitory capsid-binding host proteins TRIM5α and CPSF6, and that inhibition is not a consequence of increased binding of inhibitory factors to the viral capsid. My work also demonstrates that CypA-dependent inhibition depends in part, on a conserved domain of HIV-1 CA which determines interactions with host nuclear pore proteins. These results suggest a common mechanism underlies the ability of CypA to stimulate HIV-1 infectivity in some cells and to inhibit infection in others.

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