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Fidelity of HIV-1 reverse transcriptase.

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.

Pubmed ID: 2460924

Authors

  • Preston BD
  • Poiesz BJ
  • Loeb LA

Journal

Science (New York, N.Y.)

Publication Data

November 25, 1988

Associated Grants

  • Agency: NCI NIH HHS, Id: CA-07263-03
  • Agency: NIAID NIH HHS, Id: N01AI72654
  • Agency: NCI NIH HHS, Id: R35-CA-39903

Mesh Terms

  • Avian myeloblastosis virus
  • Bacteriophage phi X 174
  • DNA
  • DNA Polymerase II
  • DNA, Viral
  • Electrophoresis, Polyacrylamide Gel
  • HIV
  • Kinetics
  • Moloney murine leukemia virus
  • Mutation
  • Nucleotides
  • RNA-Directed DNA Polymerase