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Title page for ETD etd-02092009-163700


Type of Document Dissertation
Author Yang, Ruifeng
Author's Email Address ruifeng.yang@vanderbilt.edu
URN etd-02092009-163700
Title Identification of Novel Determinants of HIV-1 Uncoating in the Capsid Protein
Degree PhD
Department Microbiology and Immunology
Advisory Committee
Advisor Name Title
Rich D'Aquila Committee Chair
Christopher Aiken Committee Member
Gerald Stubbs Committee Member
Mark Denison Committee Member
W. Gray Jerome Committee Member
Keywords
  • Uncoating
  • Postentry
  • Capsid
  • HIV-1
Date of Defense 2009-01-30
Availability unrestricted
Abstract
Uncoating of the viral core following penetration into the target cell represents a fundamentally obscure step in the HIV-1 life cycle. Our laboratory has previously reported that mutations in the CA protein that positively and negatively alter the stability of the viral capsid shell result in impaired HIV-1 infectivity, suggesting that the HIV-1 core is optimally balanced for proper uncoating in target cells. To identify additional determinants contributing to optimal HIV-1 capsid stability in CA, I identified second-site suppressors of HIV-1 uncoating mutants by serial passage. My results indicate that CA determinants outside the CypA-binding loop can modulate the dependence of HIV-1 infection on CypA. Further, based on the recently reported full-length HIV-1 hexamer structure, my data provide novel genetic evidence of HIV-1 CA direct intersubunit interactions. My results also suggest that cellular factors are involved in HIV-1 uncoating. A detailed understanding of the mechanism and determinants of HIV-1 uncoating should facilitate the development of novel antiviral therapies targeting this key step in HIV-1 infection.
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