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-s...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1988-11, Vol.242 (4882), p.1168-1171
Main Authors: Preston, Bradley D., Poiesz, Bernard J., Loeb, Lawrence A.
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Analysis
Animal cells
Avian Myeloblastosis Virus - enzymology
Bacteriophage phi X 174 - genetics
Base sequence
Biochemistry
Biological and medical sciences
DNA
DNA - biosynthesis
DNA Polymerase II - metabolism
DNA, Viral - biosynthesis
Electrophoresis, Polyacrylamide Gel
Error rates
Fundamental and applied biological sciences. Psychology
Gels
Genetic aspects
Genetic mutation
Genetic transcription
Genetics
Genomes
HIV
HIV (Viruses)
HIV - enzymology
HIV - genetics
HIV 1
Human immunodeficiency virus 1
Kinetics
Microbiology
Moloney murine leukemia virus - enzymology
Mutation
Mutation (Biology)
Nucleotide sequence
Nucleotides
Nucleotides - metabolism
Oligomers
RNA-Directed DNA Polymerase - metabolism
Transcription (Genetics)
Virions
Virology
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Summary: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 φ 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 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.2460924