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Nucleic Acids Research, 1995, Vol. 23, No. 14 2573-2578
© 1995

MOLECULAR BIOLOGY

Reverse transcriptase and substrate dependence of the RNA hypermutagenesis reaction

Miguel Angel Martinez, Monica Sala, Jean-Pierre Vartanian and Simon Wain-Hoboson*

Unitè de Rètrovirologie Molèculaire, Institute pasteur 28 rue du Dr. Roux, 75725 Paris Cedex 15, France

*To whom correspondence should be addressed

Received May 17, 1995. Accepted June 14, 1995.

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 myeloblastosls virus (AMV) and Moloney murine leukemia virus (MoMLV), the HI V-1 enzyme showed the greatest sensitivity to biased [dCTP]/[dTTP] ratios. The HI V-1 RTase was able to discriminate between dUTP, dITP and the four DNA precursors and was insensitive to pH. There was little preference for nucleotlde 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.


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