Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C.
Recently, we described a novel nucleotide template-based mechanism that may be the basis for the facilitated acquisition of the K65R resistance mutation in subtype C versus subtype B human immunodeficiency virus type 1 (HIV-1). In this article, we evaluated the effects of subtype C-specific silent polymorphisms in cell culture drug-selection experiments using nucleoside and nucleotide reverse-transcriptase inhibitors. The K65R pathway was selected more frequently in a subtype B virus that contained subtype C nucleotide polymorphisms at both positions 64 and 65 than in a wild-type NL4-3 subtype B virus. This is the first demonstration of the significance of silent nucleotide polymorphisms in the development of drug resistance.
Invernizzi
Cédric F
CF
McGill University AIDS Centre, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Medicine, McGill University, Montréal, Québec, Canada.
Coutsinos
Dimitrios
D
Oliveira
Maureen
M
Moisi
Daniela
D
Brenner
Bluma G
BG
Wainberg
Mark A
MA
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002477:Cells; D024882:Drug Resistance, Viral / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D013997:Time Factors
D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase