Sequence and drug susceptibility of subtype C reverse transcriptase from human immunodeficiency virus type 1 seroconverters in Zimbabwe.
Naturally occurring human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) variability has implications for the success of antiretroviral therapy. We determined the sequence of the polymerase-coding region of RT from virus isolates from 12 Zimbabwean individuals recently infected with HIV-1. The 12 RT sequences differed from the consensus B RT sequence at 10.5% of nucleotides and 5.8% of amino acids. Susceptibility testing of five isolates to zidovudine, didanosine, lamivudine, and nevirapine demonstrated susceptibilities similar to those of wild-type subtype B isolates. Phylogenetic analysis of 40 HIV-1 RT sequences, including the 12 Zimbabwean subtype C sequences, 11 subtype B sequences, and the 17 remaining published non-subtype B sequences showed sufficient intrasubtype RT sequence variation to differentiate subtype A, B, C, and D isolates. Five recently reported subtype C RT sequences from India grouped with the Zimbabwean subtype C sequences but had significantly less intraisolate sequence variation. Both intra- and intersubtype RT comparisons were notable for extraordinarily high ratios of synonymous to nonsynonymous differences. Although substitutions in the HIV-1 RT gene are limited by functional constraints, variation between RT sequences demonstrates phylogenetic relationships that parallel env and gag gene variation.
Shafer
R W
RW
Department of Medicine, Stanford University, California 94305, USA. rshafer@cmgm.stanford.edu
Eisen
J A
JA
Merigan
T C
TC
Katzenstein
D A
DA
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral; D016049:Didanosine / Q000494:pharmacology*; D005260:Female; D015752:Genes, env; D054303:HIV Reverse Transcriptase / Q000187:drug effects / Q000235:genetics*; D006679:HIV Seropositivity / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019829:Nevirapine; D009692:Nucleic Acid Heteroduplexes; D010802:Phylogeny; D011725:Pyridines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D015215:Zidovudine / Q000494:pharmacology*; D015030:Zimbabwe / Q000453:epidemiology
D004279:DNA, Viral; D009692:Nucleic Acid Heteroduplexes; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; D016049:Didanosine