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PubMed · 2460924

Fidelity of HIV-1 reverse transcriptase.

B D Preston·B J Poiesz·L A Loeb
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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 HIV-1 introduced base-substitution errors in DNA from the bacteriophage phi 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 much greater than A:G greater than A:A. The high error rate of HIV-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.

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Avian Myeloblastosis VirusBacteriophage phi X 174DNADNA Polymerase IIDNA, ViralElectrophoresis, Polyacrylamide GelHIVKineticsMoloney murine leukemia virusMutationNucleotidesRNA-Directed DNA PolymeraseComparative StudyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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B D Preston, B J Poiesz, L A Loeb. 1988-11-25. Fidelity of HIV-1 reverse transcriptase.. https://doi.org/10.1126/science.2460924

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