Fidelity of HIV-1 reverse transcriptase

Bradley D. Preston, Bernard J. Poiesz, Lawrence A. Loeb

Research output: Contribution to journalArticlepeer-review

676 Scopus citations

Abstract

The human immunodeficiency virus type 1 (HIV-1) shows extensive genetic variation and undergoes rapid evolution. The fidelity of purified HIV-1 reverse transcriptase was measured during DNA polymerization in vitro by means of three different assays. Reverse transcriptase from HIY-1 introduced base-substitution errors in DNA from the bacteriophage +X174 amber3 at estimated frequencies of 1/2000 to 1/4000. Analyses of misincorporation rates opposite a single template adenine residue showed that HIV-1 reverse transcriptase catalyzed nucleotide mismatches with a specificity of A:C ≫ A:G > A:A. The high error rate of HIlV-1 reverse transcriptase in vitro translates to approximately five to ten errors per HIV-1 genome per round of replication in vivo. This high error rate suggests that misincorporation by HIV-1 reverse transcriptase is, at least in part, responsible for the hypermutability of the AIDS virus. The specificity of misincorporation may provide a basis for the systematic construction of antiviral nucleosides.

Original languageEnglish (US)
Pages (from-to)1168-1171
Number of pages4
JournalScience
Volume242
Issue number4882
DOIs
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • General

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