Sendai virus C proteins regulate viral genome and antigenome synthesis to dictate the negative genome polarity.

Sendai virus C proteins regulate viral genome and antigenome synthesis to dictate the negative genome polarity.
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仙台病毒 C 蛋白调节病毒基因组和反基因组合成,以决定负基因组极性。

DOI:
10.1128/jvi.02798-13
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发表时间:
2014
影响因子:
5.4
通讯作者:
T.
T.
中科院分区:
医学2区
文献类型:
--
作者:
Irie;T.;Okamoto;I.;Yoshida;A.;Nagai;Y.;Sakaguchi;T.

文献摘要

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单负链RNA病毒目包含大量非节段负链RNA病毒(NNSV)。基因组极性是如何确定的是RNA病毒生物学的一个中心问题。以水泡性口炎病毒(VSV)为原型,病毒基因组的负极性完全由位于基因组和反基因组3′端的不同强度的膜作用复制启动子决定,导致基因组相对于反基因组的优势。这种VSV范式长期以来一直适用于一般的单负加病毒目,没有具体的证据。我们现在发现,另一个原型物种,仙台病毒(SeV),经历了一个显着的转变,从早期的抗原组占主导地位的基因组占主导地位的阶段,在感染过程中。这种转变似乎主要由辅助C蛋白的表达决定,因为在C基因缺失的重组SeV中没有发生这种转变,并且抗原组在整个感染过程中占主导地位,产生抗原组主导和非感染性的后代病毒粒子。因此,我们首次提出了一种反式调节机制,即SeV范式,来决定NNSV的基因组极性。一系列启动子交换SeV重组体表明启动子的一级和二级结构在该转基因调控中的重要性。
The order Mononegavirales comprises a large number of nonsegmented negative-strand RNA viruses (NNSVs). How the genome polarity is determined is a central issue in RNA virus biology. Using a prototypic species, vesicular stomatitis virus (VSV), it has been established that the negative polarity of the viral genome is defined solely by different strengths of thecis-acting replication promoters located at the 3′ ends of the genome and antigenome, resulting in the predominance of the genome over the antigenome. This VSV paradigm has long been applied for the Mononegavirales in general without concrete proof. We now found that another prototypic species, Sendai virus (SeV), undergoes a marked shift from the early antigenome-dominant to the late genome-dominant phase during the course of infection. This shift appeared to be governed primarily by the expression of the accessory C protein, because no such shift occurred in a recombinant SeV with the C gene deleted, and antigenomes were dominant throughout infection, generating antigenome-dominant and noninfectious progeny virions. Therefore, we proposed for the first time atrans-regulatory mechanism, the SeV paradigm, to dictate the genome polarity of an NNSV. A series of promoter-swapped SeV recombinants suggested the importance of the primary as well as secondary structures of the promoters in thistrans-regulation.