Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase - PubMed (original) (raw)

. 1996 Mar 1;271(5253):1282-5.

doi: 10.1126/science.271.5253.1282.

W C Drosopoulos, H Salomon, M Hsu, G Borkow, M Parniak, Z Gu, Q Song, J Manne, S Islam, G Castriota, V R Prasad

Affiliations

• PMID: 8638110
• DOI: 10.1126/science.271.5253.1282

Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase

M A Wainberg et al. Science. 1996.

Abstract

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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Comment in

• Reverse transcriptase fidelity and HIV-1 variation.
  Preston BD. Preston BD. Science. 1997 Jan 10;275(5297):228-9; author reply 230-1. doi: 10.1126/science.275.5297.228. Science. 1997. PMID: 8999549 No abstract available.
• Reverse transcriptase fidelity and HIV-1 variation.
  Keulen W, Nijhuis M, Schuurman R, Berkhout B, Boucher C. Keulen W, et al. Science. 1997 Jan 10;275(5297):229; author reply 230-1. Science. 1997. PMID: 8999550 No abstract available.
• Reverse transcriptase fidelity and HIV-1 variation.
  Balzarini J, Pelemans H, De Clercq E, Karlsson A, Kleim JP. Balzarini J, et al. Science. 1997 Jan 10;275(5297):229-30; author reply 230-1. Science. 1997. PMID: 8999551 No abstract available.

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