PMID: 7512722Apr 12, 1994Paper

G-->A hypermutation of the human immunodeficiency virus type 1 genome: evidence for dCTP pool imbalance during reverse transcription

Proceedings of the National Academy of Sciences of the United States of America
Jean-Pierre VartanianS Wain-Hobson

Abstract

The quasispecies model for RNA viruses predicts the existence of a replication error threshold beyond which there is a melting or total loss of sequence information. Retroviral G-->A hypermutation is probably an example. Here it is shown that G-->A transitions may occur in both GpG and GpA dinucleotide contexts. Transitions in GpG preferentially occur via base mispairing at the ends of runs of G residues, whereas G-->A transitions within GpA may result from temporary dislocation of the primer and template strands by a single base. The two circumstances may be related by the local dCTP substrate concentration. An in vitro elongation assay shows that primer/template dislocation is more frequent for the human immunodeficiency virus type 1 reverse transcriptase than for murine or avian retroviral enzymes. Taken together these data suggest that G-->A hypermutation is an example of induced mutation whereby the viral reverse transcriptase is forced into making errors by imbalances in the intracellular dCTP concentration.

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Citations

Aug 6, 1998·Journal of Biomedical Science·N Coudronnière, C Devaux
Jan 1, 1996·Trends in Microbiology·B D Preston, J P Dougherty
Oct 15, 2003·Trends in Molecular Medicine·Jean-Pierre VartanianSimon Wain-Hobson
Oct 12, 2001·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·Elena CarideAmilcar Tanuri
Jan 26, 2010·Expert Reviews in Molecular Medicine·John S Albin, Reuben S Harris
May 26, 1999·The New England Journal of Medicine·L ZhangD D Ho
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·M A MartinezS Wain-Hobson
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·T B Kepler, A S Perelson
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·T LeitnerJ Albert
Nov 13, 2012·Journal of Biomolecular Structure & Dynamics·Alexandra E Rapoport, Edward N Trifonov
Feb 13, 2002·AIDS Research and Human Retroviruses·Ben BerkhoutVladimir V Lukashov
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