The PRRSV replicase: exploring the multifunctionality of an intriguing set of nonstructural proteins.
The PRRSV replicase: exploring the multifunctionality of an intriguing set of nonstructural proteins.
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DOI：
10.1016/j.virusres.2010.07.030
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发表时间：
2010-12
期刊：
影响因子：
5
通讯作者：
Snijder EJ
中科院分区：
文献类型：
--
作者：
Fang Y;Snijder EJ
近年来，我们对动脉炎病毒复制酶基因编码的非结构蛋白（nsps）的结构和功能有了更深入的了解。动脉炎病毒原型马动脉炎病毒的nsps的持续表征不仅证实了几个重要的功能预测，而且还揭示了动脉炎病毒复制的各种新特征。针对猪繁殖与呼吸综合征病毒（PRRSV），基于生物信息学预测和实验研究，构建了pp 1a和pp 1ab复制酶多聚蛋白的加工图谱。已经解析了两种具有蛋白酶活性的PRRSV非结构蛋白（nsp 1 α和nsp 4）的晶体结构。动脉炎病毒RNA合成的关键酶，nsp 9 RNA聚合酶和nsp 10解旋酶的功能表征已经开始。此外，已经取得了进展nsp功能有关的调节亚基因组mRNA的合成（nsp 1），诱导复制相关的膜重排（nsp 2和nsp 3），和一个有趣的复制核糖核酸内切酶（nsp 11）的天然底物仍有待确定。nsps在病毒发病机制和宿主免疫中的作用也正在探索中，并且特异性nsps（包括nsp 1 α/β、nsp 2、nsp 4、nsp 7和nsp 11）已经涉及调节宿主对PRRSV感染的免疫应答。nsp 3 -8区域被确定为含有主要的毒力因子，尽管机制信息很少。PRRSV nsps在病毒-宿主相互作用中的生物学意义以及通过反向遗传学改造PRRSV基因组的技术进步也反映在疫苗和诊断测定领域的最新发展中。
Our knowledge about the structure and function of the nonstructural proteins (nsps) encoded by the arterivirus replicase gene has advanced in recent years. The continued characterization of the nsps of the arterivirus prototype equine arteritis virus has not only corroborated several important functional predictions, but also revealed various novel features of arteriviral replication. For porcine reproductive and respiratory syndrome virus (PRRSV), based on bioinformatics predictions and experimental studies, a processing map for the pp1a and pp1ab replicase polyproteins has been developed. Crystal structures have been resolved for two of the PRRSV nonstructural proteins that possess proteinase activity (nsp1α and nsp4). The functional characterization of the key enzymes for arterivirus RNA synthesis, the nsp9 RNA polymerase and nsp10 helicase, has been initiated. In addition, progress has been made on nsp functions relating to the regulation of subgenomic mRNAs synthesis (nsp1), the induction of replication-associated membrane rearrangements (nsp2 and nsp3), and an intriguing replicative endoribonuclease (nsp11) for which the natural substrate remains to be identified. The role of nsps in viral pathogenesis and host immunity is also being explored, and specific nsps (including nsp1α/β, nsp2, nsp4, nsp7, and nsp11) have been implicated in the modulation of host immune responses to PRRSV infection. The nsp3–8 region was identified as containing major virulence factors, although mechanistic information is scarce. The biological significance of PRRSV nsps in virus-host interactions and the technical advancements in engineering the PRRSV genome by reverse genetics are also reflected in recent developments in the area of vaccines and diagnostic assays.
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影响因子：
5.4
作者：
Castillo-Olivares, J;Wieringa, R;Rottier, PJM
通讯作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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