E. Cherry et al., MUTATIONS AT CODON-184 IN SIMIAN IMMUNODEFICIENCY VIRUS REVERSE-TRANSCRIPTASE CONFER RESISTANCE TO THE (-) ENANTIOMER OF 2',3'-DIDEOXY-3'-THIACYTIDINE, Antimicrobial agents and chemotherapy, 41(12), 1997, pp. 2763-2765
Variants of simian immunodeficiency virus (SIV) that display greater t
han 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-th
iacytidine (3TC) were generated through in vitro passage and drug sele
ction. The polymerase regions of several of these resistant viruses we
re sequenced and were found to share either of two codon alterations a
t site 184 in reverse transcriptase (ATG to ATA [methionine to isoleuc
ine] and ATG to GTA [methionine to valine]). The biological relevance
of these substitutions for 3TC was confirmed by site-directed mutagene
sis with the SIVmac239 infectious recombinant clone of SIV.