3'-Azido-3'-deoxythymidine (AZT) and AZT-resistant reverse transcriptase can increase the in vivo mutation rate of human immunodeficiency virus type 1

L. M. Mansky, L. C. Bernard

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

How antiretroviral drug resistance influences human immunodeficiency virus type 1 (HIV-1) evolution is not clear. This study tested the hypothesis that antiretroviral drugs such as 3'-azido-3'-deoxythymidine (AZT) can influence the in vivo mutation rate of HIV-1. It was observed that AZT can increase the rate of HIV-1 mutation by a factor of 7 in a single round of replication. In addition, (-)2',3'-dideoxy-3'-thiacytidine (3TC) was also found to increase the mutation rate of HIV-1 by a factor of 3. It was also found that HIV-1 drug-resistant reverse transcriptase (RT) variants can influence the in vivo mutation rate. Replication of HIV-1 with AZT-resistant RTs increased the mutation rate by as much as a factor of 3, while replication of HIV-1 with a 3TC-resistant RT (M184V) had no significant effect on the mutation rate. It was observed that only high-level, AZT-resistant RT variants could influence the in vivo mutation rate (i.e., M41L/T215Y and M41L/D67N/K70R/T215Y). In total, these observations indicate that both antiretroviral drugs and drug resistance mutations can influence the in vivo mutation rate of HIV-1.

Original languageEnglish (US)
Pages (from-to)9532-9539
Number of pages8
JournalJournal of virology
Volume74
Issue number20
DOIs
StatePublished - 2000

Bibliographical note

Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.

Fingerprint Dive into the research topics of '3'-Azido-3'-deoxythymidine (AZT) and AZT-resistant reverse transcriptase can increase the in vivo mutation rate of human immunodeficiency virus type 1'. Together they form a unique fingerprint.

Cite this