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Investigation of host and viral genetic factors influencing HIV-1 evolution across North America: implications for vaccine design

Resource type
Thesis type
(Thesis) M.P.H.
Date created
2012-04-16
Authors/Contributors
Abstract
Human leukocyte antigen (HLA) class I restricted cytotoxic T-lymphocyte (CTL) responses drive HIV-1 evolution through the selection of immune escape mutations, however, the extent to which population-level patterns of immune escape have changed over the course of the HIV-1 epidemic in North America remains incompletely known. The objective of this thesis was to explore how immune selection pressures mediated through host HLA-restricted CTL responses have shaped the genomic and functional evolution of the HIV-1 gag gene over the course of the epidemic in North America. Results support the continued dynamic adaptation of HIV-1 as it passes through human hosts rather than the substantial accumulation of escape mutations over the course of the epidemic in North America. Additionally, only modest increases in gag-mediated replication capacity between pre- and post-1985 sequences were observed. Although the mechanism(s) behind these increases remain unknown, they may be attributable to factors other than CTL-driven immune responses.
Document
Identifier
etd7176
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Copyright is held by the author.
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The author granted permission for the file to be printed and for the text to be copied and pasted.
Scholarly level
Supervisor or Senior Supervisor
Thesis advisor: Brumme, Zabrina
Member of collection
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etd7176_LCotton.pdf 5.04 MB

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