Fidelity of HIV-1 reverse transcriptase

Science. 1988 Nov 25;242(4882):1168-71. doi: 10.1126/science.2460924.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Avian Myeloblastosis Virus / enzymology
  • Bacteriophage phi X 174 / genetics
  • DNA / biosynthesis*
  • DNA Polymerase II / metabolism
  • DNA, Viral / biosynthesis
  • Electrophoresis, Polyacrylamide Gel
  • HIV / enzymology*
  • HIV / genetics
  • Kinetics
  • Moloney murine leukemia virus / enzymology
  • Mutation
  • Nucleotides / metabolism
  • RNA-Directed DNA Polymerase / metabolism*

Substances

  • DNA, Viral
  • Nucleotides
  • DNA
  • RNA-Directed DNA Polymerase
  • DNA Polymerase II