dc.creator | Yang, Ruifeng | |
dc.date.accessioned | 2020-08-21T21:00:21Z | |
dc.date.available | 2011-02-10 | |
dc.date.issued | 2009-02-10 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-02092009-163700 | |
dc.identifier.uri | http://hdl.handle.net/1803/10547 | |
dc.description.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. | |
dc.format.mimetype | application/pdf | |
dc.subject | Uncoating | |
dc.subject | Postentry | |
dc.subject | Capsid | |
dc.subject | HIV-1 | |
dc.title | Identification of Novel Determinants of HIV-1 Uncoating in the Capsid Protein | |
dc.type | dissertation | |
dc.contributor.committeeMember | W. Gray Jerome | |
dc.contributor.committeeMember | Gerald Stubbs | |
dc.contributor.committeeMember | Mark Denison | |
dc.contributor.committeeMember | Christopher Aiken | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2011-02-10 | |
local.embargo.lift | 2011-02-10 | |
dc.contributor.committeeChair | Rich D'Aquila | |