Reverse transcriptase and substrate dependence of the RNA hypermutagenesis reaction.
G-->A hypermutation is a remarkable phenomenon resulting from retroviral reverse transcription in the presence of highly biased dNTP concentrations. Of the three reverse transcriptases (RTases) available, those of human immunodeficiency virus type 1 (HIV-1), avian myeloblastosis virus (AMV) and Moloney murine leukemia virus (MoMLV), the HIV-1 enzyme showed the greatest sensitivity to biased [dCTP]/[dTTP] ratios. The HIV-1 RTase was able to discriminate between dUTP, dITP and the four DNA precursors and was insensitive to pH. There was little preference for nucleotide contexts. A few exceptionally modified sequences were found presumably resulting from G-->A hypermutation and multiple strand transfer. This particular predilection of the HIV-1 and, by extrapolation, the lentiviral RTases towards G-->A hypermutation suggests that the phenomenon may have contributed to the remarkably elevated A content of these retroviral genomes.
Martínez
M A
MA
Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
Sala
M
M
Vartanian
J P
JP
Wain-Hobson
S
S
D009189:Avian Myeloblastosis Virus / Q000201:enzymology / Q000235:genetics; D001482:Base Composition; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D003854:Deoxyribonucleotides / Q000378:metabolism; D016679:Genome, Viral; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000201:enzymology / Q000235:genetics; D016296:Mutagenesis; D009843:Oligoribonucleotides / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D013379:Substrate Specificity
D017931:DNA Primers; D004279:DNA, Viral; D003854:Deoxyribonucleotides; D009843:Oligoribonucleotides; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase