The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production.

The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production.
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人冠状病毒 229E 的 ORF4a 蛋白充当调节病毒产生的病毒孔蛋白

DOI:
10.1016/j.bbamem.2013.07.025
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发表时间:
2014-04
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Sun B
Sun B
中科院分区:
其他
文献类型:
--
作者:
Zhang R;Wang K;Lv W;Yu W;Xie S;Xu K;Schwarz W;Xiong S;Sun B

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除了一组典型的基因,冠状病毒编码额外的辅助蛋白。位于刺突和包膜基因之间的基因座在所有冠状病毒中是保守的,并且包含完整或截短的开放阅读框(ORF)。以前,我们证明,这个位点,其中包含的基因从严重急性呼吸综合征冠状病毒(SARS-CoV)的辅助蛋白3a,编码的蛋白质,形成离子通道和调节病毒的释放。在本研究中,我们探讨了HCoV-229 E的ORF 4a蛋白是否具有类似的功能。我们的研究结果表明,ORF 4a蛋白在感染细胞中表达,并定位于内质网/高尔基体中间室(ERGIC)。ORF 4a蛋白通过二硫键形成同源寡聚体,在非洲爪蟾卵母细胞和酵母中均具有离子通道活性。基于对不同一价阳离子的电导测量,ORF 4a被建议形成一价阳离子的非选择性通道,尽管Li+部分地降低了内向电流。此外,当感染细胞中的ORF 4a蛋白表达被siRNA抑制时,病毒产生减少。总的来说,这些证据表明HCoV-229 E ORF 4a蛋白在功能上类似于SARS-CoV 3a蛋白,后者也作为一种病毒孔蛋白调节病毒的产生。这篇文章是一个特殊问题的一部分,题为:病毒膜蛋白-细胞网络通道。HCoV-229 E ORF 4a蛋白在感染的Huh-7细胞中表达并定位于ERGIC。ORF 4a在非洲爪蟾卵母细胞和酵母中形成同源寡聚体并作为离子通道。ORF 4a蛋白是一价阳离子的非选择性通道。HCoV-229 E ORF 4a蛋白作为病毒孔蛋白调节病毒的产生。
In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both Xenopus oocytes and yeast. Based on the measurement of conductance to different monovalent cations, the ORF4a was suggested to form a non-selective channel for monovalent cations, although Li+ partially reduced the inward current. Furthermore, viral production decreased when the ORF4a protein expression was suppressed by siRNA in infected cells. Collectively, this evidence indicates that the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV 3a protein, which also acts as a viroporin that regulates virus production. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking. HCoV-229E ORF4a protein is expressed in the infected Huh-7 cells and localized in the ERGIC. ORF4a forms homo-oligomers and serves as ion channels in both Xenopus oocytes and yeast. ORF4a protein is a non-selective channel for monovalent cations. HCoV-229E ORF4a protein acts as viroporins to regulate the virus production.
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