Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus Propagation
Endoplasmic Reticulum-Associated Degradation Controls Virus Protein Homeostasis, Which Is Required for Flavivirus Propagation
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内质网相关降解控制病毒蛋白稳态，这是黄病毒繁殖所必需的
DOI：
10.1128/jvi.02234-20
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发表时间：
2021
影响因子：
5.4
通讯作者：
Morita Eiji
中科院分区：
文献类型：
--
作者：
Tabata Keisuke;Arakawa Masashi;Ishida Kotaro;Kobayashi Makiko;Nara Atsuki;Sugimoto Takehiro;Okada Tetsuya;Mori Kazutoshi;Morita Eiji
许多正链RNA病毒编码多聚蛋白，通过加工多聚蛋白产生病毒蛋白。该系统产生等量的每种病毒蛋白质，尽管每种蛋白质所需的量不同。在本研究中，我们发现日本脑炎病毒和登革病毒的膜外锚定非结构（NS）蛋白通过内质网相关降解（ERAD）途径被快速和选择性地降解。我们的基因靶向研究表明，ERAD涉及Derlin 2和SEL 1 L，而不是Derlin 1，是病毒基因组复制所必需的。Derlin 2主要定位于病毒复制细胞器的卷曲膜（CM）中，并且病毒NS蛋白在CM中降解。因此，这些结果表明，病毒蛋白质的稳态是由Derlin 2介导的ERAD在CM调节，这个过程是至关重要的，这些virus.IMPORTANCEThe研究结果显示，细胞ERAD系统控制的病毒感染的细胞中的每个病毒蛋白质的量，这种“病毒蛋白质的稳态”是病毒繁殖的关键。此外，我们澄清了“卷曲膜（CM）”，这是以前被认为是一个结构与未知的功能，作为一种废物倾倒在病毒蛋白降解发生。我们还发现，Derlin 2/SEL 1 L/HRD 1特异性途径参与了这一过程，而Derlin 1介导的途径则没有。这种新的ERAD介导的微调系统的化学计量的多蛋白衍生的病毒蛋白质可能代表了一个共同的特点之间的多蛋白编码病毒。
Many positive-stranded RNA viruses encode polyproteins from which viral proteins are generated by processing the polyproteins. This system produces an equal amount of each viral protein, though the required amounts for each protein are not the same. In this study, we found the extra membrane-anchored nonstructural (NS) proteins of Japanese encephalitis virus and dengue virus are rapidly and selectively degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway. Our gene targeting study revealed that ERAD involving Derlin2 and SEL1L, but not Derlin1, is required for the viral genome replication. Derlin2 is predominantly localized in the convoluted membrane (CM) of the viral replication organelle, and viral NS proteins are degraded in the CM. Hence, these results suggest that viral protein homeostasis is regulated by Derlin2-mediated ERAD in the CM, and this process is critical for the propagation of these viruses.IMPORTANCEThe results of this study reveal the cellular ERAD system controls the amount of each viral protein in virus-infected cells and that this “viral protein homeostasis” is critical for viral propagation. Furthermore, we clarified that the “convoluted membrane (CM),” which was previously considered a structure with unknown function, serves as a kind of waste dump where viral protein degradation occurs. We also found that the Derlin2/SEL1L/HRD1-specific pathway is involved in this process, whereas the Derlin1-mediated pathway is not. This novel ERAD-mediated fine-tuning system for the stoichiometries of polyprotein-derived viral proteins may represent a common feature among polyprotein-encoding viruses.
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影响因子：
5.4
作者：
Kujala, P;Ahola, T;Kääriäinen, L
通讯作者：
Kääriäinen, L
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
13.8
作者：
Hwang J;Qi L
通讯作者：
Qi L
影响因子：
1.5
作者：
Takehiro Sugimoto;Satoshi Ninagawa;Shimpei Yamano;Tokiro Ishikawa;T. Okada;S. Takeda;K. Mori
通讯作者：
Takehiro Sugimoto;Satoshi Ninagawa;Shimpei Yamano;Tokiro Ishikawa;T. Okada;S. Takeda;K. Mori
影响因子：
5.9
作者：
Yost, Samantha A.;Marcotrigiano, Joseph
通讯作者：
Marcotrigiano, Joseph