Martínez M A, Sala M, Vartanian J P, Wain-Hobson S
Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
Nucleic Acids Res. 1995 Jul 25;23(14):2573-8. doi: 10.1093/nar/23.14.2573.
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.
G→A超突变是一种在高度偏向性的脱氧核苷酸三磷酸(dNTP)浓度存在下,由逆转录病毒逆转录产生的显著现象。在三种可用的逆转录酶(RTases)中,即人类免疫缺陷病毒1型(HIV-1)、禽成髓细胞瘤病毒(AMV)和莫洛尼鼠白血病病毒(MoMLV)的逆转录酶,HIV-1酶对偏向性的[dCTP]/[dTTP]比率表现出最大的敏感性。HIV-1逆转录酶能够区分脱氧尿苷三磷酸(dUTP)、脱氧肌苷三磷酸(dITP)和四种DNA前体,并且对pH不敏感。对核苷酸上下文几乎没有偏好。发现了一些异常修饰的序列,推测是由G→A超突变和多链转移导致的。HIV-1以及由此推断的慢病毒逆转录酶对G→A超突变的这种特殊偏好表明,该现象可能导致了这些逆转录病毒基因组中A含量的显著升高。