Vartanian J P, Meyerhans A, Sala M, Wain-Hobson S
Unité de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3092-6. doi: 10.1073/pnas.91.8.3092.
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.
RNA病毒的准种模型预测存在一个复制错误阈值，超过该阈值会出现序列信息的熔解或完全丧失。逆转录病毒的G→A超突变可能就是一个例子。本文表明，G→A转换可能发生在GpG和GpA二核苷酸环境中。GpG中的转换优先通过G残基连续序列末端的碱基错配发生，而GpA内的G→A转换可能是由于引物和模板链单碱基的暂时错位导致的。这两种情况可能与局部dCTP底物浓度有关。体外延伸试验表明，人类免疫缺陷病毒1型逆转录酶比鼠类或禽类逆转录病毒酶更容易发生引物/模板错位。综合这些数据表明，G→A超突变是诱导突变的一个例子，即病毒逆转录酶因细胞内dCTP浓度失衡而被迫出错。
