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人副流感病毒2型副粘病毒抗原组在感染过程中发生编辑的证据。

Evidence that hPIV2 paramyxovirus antigenomes are edited during infection.

作者信息

Ohta Keisuke, Kawasaki Junna, Kolakofsky Daniel, Nishio Machiko, Matsumoto Yusuke

机构信息

Department of Microbiology, School of Medicine, Wakayama Medical University, Wakayama, Japan.

Graduate School of Medicine, Chiba University, Chiba, Japan.

出版信息

mBio. 2025 Aug 13;16(8):e0366724. doi: 10.1128/mbio.03667-24. Epub 2025 Jun 24.

Abstract

UNLABELLED

Mononegavirus genomes contain -acting sequences that direct the formation of mRNA 5' and 3' ends during synthesis (gene start [GS] and gene end [GE]) but are silent during antigenome synthesis from the same genome template. Paramyxo- and filoviruses also carry an additional -acting sequence (EDIT) that directs the insertion of specific nucleotide during mRNA synthesis, expanding gene products. This "mRNA editing" is associated with viruses whose replication is governed by the rule of six. One might, therefore, assume that EDIT, like GS and GE, would be restricted to that of mRNA synthesis. However, accurate determination of the ratio of edited to unedited RNAs in different sub-populations of wild-type and mutant human parainfluenza virus type 2 (hPIV2) infections finds evidence that antigenomes are also edited during infection. This alters our view of how the rule of six governs mononegavirus infections and why this rule, RNA editing, and bipartite promoters are linked.

IMPORTANCE

We have assumed that paramyxovirus editing signals would operate strictly during mRNA synthesis, as it apparently makes no sense to edit antigenomes. Nevertheless, there is evidence here that the opposite is the case. If so, this alters our view of paramyxovirus replication, and we summarize what is known about how its RNA-dependent RNA polymerase carries out its task of expressing alternate open reading frames during mRNA synthesis.

摘要

未标记

单股负链病毒基因组包含在合成过程中指导mRNA 5'和3'末端形成的顺式作用序列(基因起始[GS]和基因末端[GE]),但在从同一基因组模板合成反基因组时不发挥作用。副粘病毒和丝状病毒还携带一个额外的顺式作用序列(编辑序列[EDIT]),该序列在mRNA合成过程中指导特定核苷酸的插入,从而增加基因产物。这种“mRNA编辑”与复制受六规则支配的病毒有关。因此,有人可能会认为,EDIT与GS和GE一样,仅限于mRNA合成。然而,准确测定野生型和突变型2型人副流感病毒(hPIV2)感染不同亚群中编辑RNA与未编辑RNA的比例,发现有证据表明反基因组在感染过程中也会被编辑。这改变了我们对六规则如何控制单股负链病毒感染以及该规则、RNA编辑和二分启动子为何相关的看法。

重要性

我们一直认为副粘病毒编辑信号仅在mRNA合成过程中起作用,因为编辑反基因组显然没有意义。然而,这里有证据表明情况恰恰相反。如果是这样,这就改变了我们对副粘病毒复制的看法,我们总结了关于其依赖RNA的RNA聚合酶在mRNA合成过程中如何执行表达交替开放阅读框任务的已知信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18c1/12345181/f5599f0b2890/mbio.03667-24.f001.jpg

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