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Identification of Novel Determinants of HIV-1 Uncoating in the Capsid Protein

dc.creatorYang, Ruifeng
dc.date.accessioned2020-08-21T21:00:21Z
dc.date.available2011-02-10
dc.date.issued2009-02-10
dc.identifier.urihttps://etd.library.vanderbilt.edu/etd-02092009-163700
dc.identifier.urihttp://hdl.handle.net/1803/10547
dc.description.abstractUncoating 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.
dc.format.mimetypeapplication/pdf
dc.subjectUncoating
dc.subjectPostentry
dc.subjectCapsid
dc.subjectHIV-1
dc.titleIdentification of Novel Determinants of HIV-1 Uncoating in the Capsid Protein
dc.typedissertation
dc.contributor.committeeMemberW. Gray Jerome
dc.contributor.committeeMemberGerald Stubbs
dc.contributor.committeeMemberMark Denison
dc.contributor.committeeMemberChristopher Aiken
dc.type.materialtext
thesis.degree.namePHD
thesis.degree.leveldissertation
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorVanderbilt University
local.embargo.terms2011-02-10
local.embargo.lift2011-02-10
dc.contributor.committeeChairRich D'Aquila


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