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dc.contributor.advisorSarafianos, Stefan G.eng
dc.contributor.authorFlores, Jacqueline A.eng
dc.date.issued2017eng
dc.date.submitted2017 Springeng
dc.description.abstract[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Two classes of drugs: nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) target HIV-1 RT, an enzyme required for HIV replication. The first generation NNRTIs (nevirapine and efavirenz) have been extensively used worldwide. However, they have a low genetic barrier for resistance. The second generation NNRTI, Rilpivirine (RPV) is effective against viruses that are resistant to nevirapine and efavirenz. RPV has not been used against subtype C HIV-1, which accounts for [about]50% of all infections. Recent clinical trials have shown that patients with subtype C are more likely to fail RPV-based treatment. However, the mechanism of RPV-failure has not been determined. To get insight into RPV-failure, RTs from patient isolates were cloned and biochemically characterized using pre-steady state kinetics to determine: 1) the impact of genetic variation on HIV-1 replication, and 2) the effect of a known RPVresistance mutation (p66E138K-M184I/p51E138K) on the initiation of reverse transcription, the first step of HIV replication. The results showed that subtype C HIV-1 RT has lower DNA and dNTP binding affinities, and RPV binding affinity than subtype B HIV-1 RT. The p66E138K-M184I/p51E138K mutation was found to cause rilpivirine to dissociate from p66E138KM184I/p51E138K RT 3x faster than wild type RT at initiation suggesting that RPV may not be an optimal choice for that subtype C infections.eng
dc.identifier.urihttps://hdl.handle.net/10355/62017
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess is limited to the University of Missouri--Columbiaeng
dc.sourceSubmitted by the University of Missouri--Columbia Graduate School.eng
dc.subject.FASTReverse transcriptaseeng
dc.subject.FASTDrug resistanceeng
dc.subject.FASTHIV (Viruses)eng
dc.titleBiochemical characterization of clade B and non-B HIV-1 reverse transcriptaseeng
dc.typeThesiseng
thesis.degree.disciplineMicrobiology (Medicine) (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelMasterseng
thesis.degree.nameM.S.eng


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