Thesis(Ph.D.)--Case Western Reserve University, 2010 / Title from PDF (viewed on 2009-12-22) Department of Chemistry Includes abstract Includes bibliographical references and appendices Available online via the OhioLINK ETD Center

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

No description available.

Not available / text

This thesis project was designed to investigate the phenotypic and genotypic variability of human immunodeficiency virus type 1 (HIV-1) drug-naive clade C reverse transcriptase (RT) and its potential impact in the development of resistance against inhibitors of RT. Five treatment-naive HIV-1 Ethiopian isolates were classified as subtype C on the basis of env gene heteroduplex mobility assays (HMA) profile and phylogenetic analysis of RT sequences. In subtype C RT, a specific KVEQ motif of silent mutations (amino acid 65, 106, 138, 161) at resistance sites was present. Two Ethiopian strains were naturally resistant to non-nucleoside RT inhibitors (NNRTI), as well as to zidovudine (ZDV), based on the natural polymorphisms of G190A and K70R, respectively. The final drug concentration that selected for NNRTI primary resistance mutations in tissue culture assays was significantly higher for clade B than clade C for each of nevirapine (NW) (10 muM versus 2 or 4 muM), efavirenz (EFV) (1muM versus 0.01muM) and delaviridine (DLV) (10muM versus 1 or 4muM), respectively. In the middle of the selection period with all the NNRTIs, subtype B viruses were harboring a mixture of both wild type and mutated forms, whereas in clade C viruses, primary resistance mutations were fully generated. Thus, we have found that clade C isolates developed more rapidly resistance (8 or 9 weeks with NVP or DLV and 13 weeks with EFV) as compared with clade B controls (at least 15 weeks with NW or DLV and 30 weeks with EFV). Odd mutations were detected during selection with NNRTIs, such as S98I, and two mutations (A62V and V75E), at sites associated to multi-drug resistance against nucleoside inhibitors (NRTIs). The substitution A62V was initially observed as a drug-naive silent mutation A62A. NW and DLV mutants were broadly cross-resistants. Following in vitro selection for drug-resistance with NNRTIs (NVP, DLV and EFV) and NRTIs [lamivudine (3TC) and ZDV], RT immunodominant regions of 14 HIV-1 s

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 126-148) Also available in print.

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Kenneth A. Johnson. Vita. Includes bibliographical references.

No description available.

Thesis (Ph. D.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains x, 200 p. : ill. Vita. Includes abstract. Includes bibliographical references.