TY - JOUR
T1 - Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase
AU - Wainberg, Mark A.
AU - Drosopoulos, William C.
AU - Salomon, Horacio
AU - Hsu, Mayla
AU - Borkow, Gadi
AU - Parniak, Michael A.
AU - Gu, Zhengxian
AU - Song, Qingbin
AU - Manne, Jayanthi
AU - Islam, Sabina
AU - Castriota, Gino
AU - Prasad, Vinayaka R.
PY - 1996/3/1
Y1 - 1996/3/1
N2 - Monotherapy with (-)2',3'-dideoxy-3'-thiacytidine (3TC) leads to the appearance of a drug-resistant variant of human immunodeficiency virus-type 1 (HIV-1) with the methionine-184 → valine (M184V) substitution in the reverse transcriptase (RT). Despite resulting drug resistance, treatment for more than 48 weeks is associated with a lower plasma viral burden than that at baseline. Studies to investigate this apparent contradiction revealed the following. (i) Titers of HIV-neutralizing antibodies remained stable in 3TC-treated individuals in contrast to rapid declines in those treated with azidothymidine (AZT). (ii) Unlike wild-type HIV, growth of M184V HIV in cell culture in the presence of d4T, AZT, Nevirapine, Delavirdine, or Saquinavir did not select for variants displaying drug resistance. (iii) There was an increase in fidelity of nucleotide insertion by the M184V mutant compared with wild-type enzyme.
AB - Monotherapy with (-)2',3'-dideoxy-3'-thiacytidine (3TC) leads to the appearance of a drug-resistant variant of human immunodeficiency virus-type 1 (HIV-1) with the methionine-184 → valine (M184V) substitution in the reverse transcriptase (RT). Despite resulting drug resistance, treatment for more than 48 weeks is associated with a lower plasma viral burden than that at baseline. Studies to investigate this apparent contradiction revealed the following. (i) Titers of HIV-neutralizing antibodies remained stable in 3TC-treated individuals in contrast to rapid declines in those treated with azidothymidine (AZT). (ii) Unlike wild-type HIV, growth of M184V HIV in cell culture in the presence of d4T, AZT, Nevirapine, Delavirdine, or Saquinavir did not select for variants displaying drug resistance. (iii) There was an increase in fidelity of nucleotide insertion by the M184V mutant compared with wild-type enzyme.
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U2 - 10.1126/science.271.5253.1282
DO - 10.1126/science.271.5253.1282
M3 - Article
C2 - 8638110
AN - SCOPUS:13344294407
SN - 0036-8075
VL - 271
SP - 1282
EP - 1285
JO - Science
JF - Science
IS - 5253
ER -
