Unselected mutations in the human immunodeficiency virus type 1 genome are mostly nonsynonymous and often deleterious.

Published

Journal Article

Mutation rates of human immunodeficiency virus type 1 (HIV-1) genomes have been estimated using purified reverse transcriptase or single-round infection system. Since small sequences were used as templates, the overall mutation rates could only be extrapolated and the biological significance of mutations is unknown. For direct estimation of HIV-1 mutation rates and understanding of the potential biological influences of mutations, we obtained 19 complete or nearly full-length proviral genomes from single-round-infected adherent cells of lymphocytes by using a lambda phage library method and a long-range PCR technique. Analysis of 160,000 bp of sequences showed that the overall mutation rate of HIV-1 genomes was 5.4 x 10(-5) per base per replication cycle. On average, 1.1 mutations (range, 0 to 3) were generated in each viral genome during one infection cycle. Inspection of the mutations in the HIV-1 genome revealed that all site mutations within protein-coding regions were nonsynonymous mutations. Among all mutations, half were deleterious (premature stop codon and deletions) and would result in defective genomes. By applying the same system to an HIV-1 genome with a G262A mutation in the thumb region of the reverse transcriptase, a significant increase was observed in deletion and insertion mutation rates but no increase in the overall mutation rate in viral genomes was found.

Full Text

Duke Authors

Cited Authors

  • Gao, F; Chen, Y; Levy, DN; Conway, JA; Kepler, TB; Hui, H

Published Date

  • March 2004

Published In

Volume / Issue

  • 78 / 5

Start / End Page

  • 2426 - 2433

PubMed ID

  • 14963138

Pubmed Central ID

  • 14963138

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.78.5.2426-2433.2004

Language

  • eng

Conference Location

  • United States