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Fidelity of HIV-1 reverse transcriptase.

Science (New York, N.Y.) | Nov 25, 1988

http://www.ncbi.nlm.nih.gov/pubmed/2460924

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 RIS Download

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