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dc.contributor.supervisor Plummer,Frank (Medical Microbiology and Infectious Diseases) Ball, Blake (Medical Microbiology and Infectious Diseases) en
dc.contributor.author De, Sujata Monika
dc.date.accessioned 2011-04-12T17:01:53Z
dc.date.available 2011-04-12T17:01:53Z
dc.date.issued 2011-04-12T17:01:53Z
dc.identifier.uri http://hdl.handle.net/1993/4523
dc.description.abstract APOBEC3 proteins, in particular APOBEC3G/F, are important innate host factors that contribute to protection from HIV-1 infection by inducing high levels of guanine to adenine nucleotide substitutions (termed hypermutation) during HIV-1 viral replication. These nucleotide substitutions occur at different rates and locations across the HIV-1 genome and are thought to be particularly more frequent in the pol region. The virus has evolved ways to counteract these host factors by inducing degradation of APOBEC3G/F proteins through protein interactions with HIV-1 Vif. The aim of this thesis is to characterize and investigate the role of APOBEC3G/F-mediated hypermutation in the HIV-1 genome. We identified a subset of women from the Pumwani Commercial Sex Worker (CSW) cohort with significantly higher rates of hypermutated proviruses in pol. This degree of hypermutation correlated to less severe HIV disease progression as measured by CD4+ T cell count. This was in agreement with previous studies that evidence of APOBEC-mediated hypermutation correlate with reduced disease progression, confirming APOBEC3G/F proteins role in HIV-1 disease. Furthermore, we investigated the in vitro and ex vivo interaction between HIV-1 Vif and APOBEC3G from subjects infected with hypermutated and non-hypermutated proviruses. In vitro studies indicated that HIV-1 Vif protein expression in subjects with hypermutated proviruses were quite divergent and levels of APOBEC3G also differed between subjects. Ex vivo studies in subjects with hypermutated proviruses indicated that endogenous APOBEC3G expression was greater than in subjects with hypermutated proviruses. Both studies suggest that host and viral factors such as APOBEC3G and HIV-1 Vif are playing an influential role in HIV-1 pathogenesis. Further investigations into these interactions may lead to novel strategies into the development of therapeutic drugs for the fight against HIV-1. en
dc.format.extent 2467634 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject HIV-1 en
dc.subject APOBEC3G en
dc.title Proviral HIV-1 hypermutation: the correlation of APOBEC3G/F and HIV-1 Vif in HIV-1 disease progression en
dc.type info:eu-repo/semantics/masterThesis
dc.degree.discipline Medical Microbiology en
dc.contributor.examiningcommittee Yao, Xiaojian (Medical Microbiology and Infectious Diseases) He, Runtao (Medical Microbiology and Infectious Diseases) Kung, Sam (Immunology) en
dc.degree.level Master of Science (M.Sc.) en
dc.description.note May 2011 en


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