Nucleoside-analog resistance mutations in HIV-1 reverse transcriptase and their influence on polymerase fidelity and viral mutation rates

Lisa F. Rezende, Vinayaka R. Prasad

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Nucleoside-analog inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) were the first drugs used against the virus. It is long known that monotherapy with these and other drugs leads to the rapid development of viral resistance and it is being increasingly appreciated that a significant percentage of individuals receiving highly active antiretroviral therapy (HAART) also develop resistance. Considering the fact that RT is responsible both for optimal rate of replication and an accurate copying of the viral genome, the consequence of drug-resistance mutations in RT to the biochemistry of this enzyme and to the biology of the virus are critically important. The biochemistry of HIV-1 reverse transcriptase variants harboring nucleoside-analog resistance mutations has been studied extensively. In this review, we describe a number of studies into the polymerase fidelity of nucleoside-analog resistant HIV-1 reverse transcriptase as well as the mutation rate of HIV-1 harboring these mutations.

Original languageEnglish (US)
Pages (from-to)1716-1734
Number of pages19
JournalInternational Journal of Biochemistry and Cell Biology
Volume36
Issue number9
DOIs
StatePublished - Sep 2004

Fingerprint

Mutation Rate
Viruses
Nucleosides
HIV-1
Biochemistry
RNA-Directed DNA Polymerase
Mutation
Pharmaceutical Preparations
Copying
Viral Genome
Highly Active Antiretroviral Therapy
Genes
Drug Resistance
Enzymes
Human immunodeficiency virus 1 reverse transcriptase

Keywords

  • Fidelity
  • HIV-1
  • Mutation rates
  • Nucleoside-analog resistance
  • Reverse transcriptase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

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