Polymorphisms of cytotoxic T-lymphocyte (CTL) and T-helper epitopes within reverse transcriptase (RT) of HIV-1 subtype C from Ethiopia and Botswana following selection of antiretroviral drug resistance.
Drug resistance is the major limiting factor in the effective therapeutic management of HIV infection with antiretroviral drugs (ARVs). In developing countries, where access to ARVs may be limited, therapeutic vaccine protocols designed to restrict the advent of drug resistance may be of interest. Whereas the immunodominant regions of HIV-1 clade B RT peptides have been well characterized, little is known about potential divergence among RTs of other HIV-1 subtypes. In this study, RT sequence polymorphisms were ascertained in phylogenetically classified subtype C isolates from treatment-nai;ve Ethiopian (n = 5) and Botswanian persons (n = 9). There were clusters of variability in some RT epitopes associated with cytotoxic T lymphocyte (CTL) and helper T cell function within subtype C viruses, although other epitopes remained conserved among subtype C and B viruses. Subtype C mutations associated with drug resistance were identified in vitro, using increasing concentrations of non-nucleoside RT inhibitors (NNRTIs) and nucleoside RT inhibitors (NRTIs). Mutations within immunogenic regions of clade C RT were noted during drug selection of subtype C isolates with nevirapine (S98I, Y181C, V108I and K103N), delavirdine, (A62V, V75E, L100I, K103T, V108I, Y181C), efavirenz (K103E, V106M, V179D, Y188C/H, G190A), lamivudine (M184I, M184V), and zidovudine (K70R), respectively. Further characterization of predicted CTL and T-helper anchor motifs and ARV-induced mutations in HIV-1 non-B subtype RTs is warranted.
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology; D001483:Base Sequence; D001902:Botswana; D002478:Cells, Cultured; D004279:DNA, Viral; D024882:Drug Resistance, Viral; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005002:Ethiopia; D015752:Genes, env; D015658:HIV Infections / Q000097:blood / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010802:Phylogeny; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase