Bluetongue virus: dissection of the polymerase complex.

Bluetongue virus: dissection of the polymerase complex.
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DOI:
10.1099/vir.0.2008/002089-0
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发表时间:
2008-08
期刊:
The Journal of general virology
影响因子:
--
通讯作者:
Roy P
Roy P
中科院分区:
其他
文献类型:
--
作者:
Roy P

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蓝舌病是反刍动物的一种媒介传播的病毒性疾病,在热带和亚热带国家流行。自1998年以来,该病毒也出现在欧洲。部分由于疾病的严重性,蓝舌病毒(BTV),呼肠孤病毒科中环状病毒属的成员,在过去三十年中一直是密集分子研究的主题,并且现在是分子和结构水平上最好理解的病毒之一。BTV是一种复杂的无包膜病毒,具有排列在两个衣壳中的七个结构蛋白和十个双链(ds)RNA片段的基因组。在进入细胞后不久,外衣壳丢失以释放内衣壳(核心),其从每个基因组区段合成加帽的mRNA,将它们挤出到细胞质中。这需要多种酶的有效协调,包括解旋酶、聚合酶和RNA加帽活性。这篇评论将集中在我们目前的理解,这些催化蛋白质来自使用重组蛋白,结合功能测定和体外重建的转录/复制复合物。在某些情况下,3D结构补充了这种分析,以揭示这些蛋白质的精细结构细节。核心酶的组合活性产生启动BTV感染所必需且足够的感染性转录物。这样的感染性转录物现在可以完全在体外合成,并且当通过转染引入细胞时,导致感染性病毒的恢复。因此,未来的研究有可能分析复制病毒系统中突变的后果。
Bluetongue is a vector-borne viral disease of ruminants that is endemic in tropical and subtropical countries. Since 1998 the virus has also appeared in Europe. Partly due to the seriousness of the disease bluetongue virus (BTV), a member of genus Orbivirus within the family Reoviridae, has been a subject of intense molecular study for the last three decades and is now one of the best understood viruses at the molecular and structural levels. BTV is a complex non-enveloped virus with seven structural proteins arranged in two capsids and a genome of ten double-stranded (ds) RNA segments. Shortly after cell entry the outer capsid is lost to release an inner capsid (the core) which synthesises capped mRNAs from each genomic segment, extruding them into the cytoplasm. This requires the efficient co-ordination of a number of enzymes including helicase, polymerase and RNA capping activities. This review will focus on our current understanding of these catalytic proteins as derived from the use of recombinant proteins, combined with functional assays and the in vitro reconstitution of the transcription/replication complex. In some cases, 3D structures have complemented this analysis to reveal the fine structural detail of these proteins. The combined activities of the core enzymes produce infectious transcripts necessary and sufficient to initiate BTV infection. Such infectious transcripts can now be synthesised wholly in vitro and, when introduced into cells by transfection, lead to the recovery of infectious virus. Future studies thus hold the possibility of analysing the consequence of mutation in a replicating virus system.
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