The G-Patch Domain of Mason-Pfizer Monkey Virus Is a Part of Reverse Transcriptase
The G-Patch Domain of Mason-Pfizer Monkey Virus Is a Part of Reverse Transcriptase
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DOI：
10.1128/jvi.06638-11
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发表时间：
2012-02-01
影响因子：
5.4
通讯作者：
Pichova, Iva
中科院分区：
文献类型：
--
作者：
Krizova, Ivana;Hadravova, Romana;Pichova, Iva
梅森-辉瑞猴病毒（M-PMV）与其他一些β逆转录病毒一样，编码G补丁结构域（GPD）。该富含甘氨酸的结构域被预测为RNA结合模块，其总是位于β逆转录病毒基因组RNA的pro-pol核糖体移码序列上游的pro基因的3'末端。在两个核糖体移码事件和病毒mRNA的翻译之后，GPD存在于Gag-Pro和Gag-Pro-Pol多聚蛋白中。在Gag-Pro多蛋白的成熟过程中，GPD暂时保持蛋白酶（PR）的C末端部分，然后通过PR本身从其脱离。Gag-Pro-Pol编码的GPD的命运仍有待确定。GPD在逆转录病毒生命周期中的功能尚不清楚。为了阐明GPD在M-PMV复制周期中的作用，对其最高度保守的残基进行丙氨酸扫描突变分析。一系列个别突变以及整个GPD的缺失对M-PMV组装、多蛋白加工和RNA掺入没有影响。然而，逆转录酶（RT）活性的减少，导致M-PMV感染性下降，确定所有GPD突变体。免疫沉淀实验表明，GPD是RT的一部分，并参与其功能。这些数据表明M-PMV GPD作为逆转录酶而不是蛋白酶的一部分发挥作用。
Mason-Pfizer monkey virus (M-PMV), like some other betaretroviruses, encodes a G-patch domain (GPD). This glycine-rich domain, which has been predicted to be an RNA binding module, is invariably localized at the 3' end of the pro gene upstream of the pro-pol ribosomal frameshift sequence of genomic RNAs of betaretroviruses. Following two ribosomal frameshift events and the translation of viral mRNA, the GPD is present in both Gag-Pro and Gag-Pro-Pol polyproteins. During the maturation of the Gag-Pro polyprotein, the GPD transiently remains a C-terminal part of the protease (PR), from which it is then detached by PR itself. The destiny of the Gag-Pro-Pol-encoded GPD remains to be determined. The function of the GPD in the retroviral life cycle is unknown. To elucidate the role of the GPD in the M-PMV replication cycle, alanine-scanning mutational analysis of its most highly conserved residues was performed. A series of individual mutations as well as the deletion of the entire GPD had no effect on M-PMV assembly, polyprotein processing, and RNA incorporation. However, a reduction of the reverse transcriptase (RT) activity, resulting in a drop in M-PMV infectivity, was determined for all GPD mutants. Immunoprecipitation experiments suggested that the GPD is a part of RT and participates in its function. These data indicate that the M-PMV GPD functions as a part of reverse transcriptase rather than protease.