Genetic and biochemical studies on the assembly of an enveloped virus.

Genetic and biochemical studies on the assembly of an enveloped virus.
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有包膜病毒组装的遗传和生化研究。

DOI:
10.1007/0-306-47572-3_6
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发表时间:
2001
期刊:
Genetic engineering
影响因子:
--
通讯作者:
Kuhn,RJ
Kuhn,RJ
中科院分区:
--
文献类型:
--
作者:
Tellinghuisen,TL;Perera,R;Kuhn,RJ

文献摘要

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辛德毕斯病毒(SINV)是披膜病毒科的有包膜正链RNA病毒的成员,并且是甲病毒属的原型病毒。甲病毒属分布于世界各地(1)。几种甲病毒是人类的重要病原体,可引起从皮疹、关节痛到致命脑炎等疾病(2)。此外,一些甲病毒是家畜的病原体。它们在自然界中通过蚊子传播,蚊子中的复制是病毒生命周期的重要阶段。甲病毒在结构、遗传和生物化学水平上得到了很好的表征。除了许多甲病毒的冷冻电子显微镜(cryo-EM)图像重建外,该属的几个成员的衣壳蛋白(CP)的一部分的结构已在原子分辨率下得到解决。病毒体的组织和组成(下文将更详细地描述)表明了一种相对简单的组装机制。使用甲病毒作为研究包膜病毒组装的模型系统进一步得到了强大的反向遗传学系统的支持。已知至少9种甲病毒的约12,000 nt基因组的全部或部分序列。感染性RNA转录物可以从这些病毒中的至少五种的cDNA克隆中产生,从而允许进行诱变并拯救突变病毒。此外,从cDNA产生的用于研究细胞培养中病毒复制和组装的系统已经被开发出来。
Sindbis virus (SINV) is a member of the Togaviridae family of enveloped, positive stranded RNA viruses, and is the prototype virus of the alphavirus genus. The alphaviruses are of worldwide distribution (1). Several of the alphaviruses are important pathogens of man, causing diseases ranging from rash and arthralgia to fatal encephalitis (2). Additionally, some alphaviruses are pathogens of domestic animals. They are transmitted in nature by mosquitoes, and replication in the mosquito is an important stage of the virus life cycle. The alphaviruses are well characterized at a structural, genetic and biochemical level. In addition to cryo-electron microscopy (cryo-EM) image reconstructions of a number of alphaviruses, the structure of a portion of the capsid protein (CP) has been solved at atomic resolution for several members of the genus. The organization and composition of the virion, described in greater detail below, suggest a relatively simple assembly mechanism. The use of the alphaviruses as a model system for studying enveloped virus assembly is further supported by the powerful reverse genetics systems available. The sequence of all or part of the approximately 12,000 nt genome is known for at least nine alphaviruses. Infectious RNA transcripts can be generated from cDNA clones for at least five of these viruses, allowing mutagenesis to be performed and mutant viruses to be rescued. Additionally generated from cDNA, systems for the study of viral replication and assembly in cell culture have been