未折叠蛋白反应
内质网
生物
翻译(生物学)
甲型流感病毒
病毒复制
细胞生物学
糖蛋白
病毒
XBP1型
血凝素(流感)
病毒学
蛋白质生物合成
病毒蛋白
接种疫苗
核糖核酸
信使核糖核酸
分子生物学
基因
遗传学
RNA剪接
作者
Beryl Mazel-Sanchez,Justyna Iwaszkiewicz,Joao P. P. Bonifacio,Filo Silva,Chengyue Niu,Shirin Strohmeier,Davide Eletto,Florian Krammer,Gene S. Tan,Vincent Zoete,Benjamin G. Hale,Mirco Schmolke
标识
DOI:10.1073/pnas.2024681118
摘要
Excessive production of viral glycoproteins during infections poses a tremendous stress potential on the endoplasmic reticulum (ER) protein folding machinery of the host cell. The host cell balances this by providing more ER resident chaperones and reducing translation. For viruses, this unfolded protein response (UPR) offers the potential to fold more glycoproteins. We postulated that viruses could have developed means to limit the inevitable ER stress to a beneficial level for viral replication. Using a relevant human pathogen, influenza A virus (IAV), we first established the determinant for ER stress and UPR induction during infection. In contrast to a panel of previous reports, we identified neuraminidase to be the determinant for ER stress induction, and not hemagglutinin. IAV relieves ER stress by expression of its nonstructural protein 1 (NS1). NS1 interferes with the host messenger RNA processing factor CPSF30 and suppresses ER stress response factors, such as XBP1. In vivo viral replication is increased when NS1 antagonizes ER stress induction. Our results reveal how IAV optimizes glycoprotein expression by balancing folding capacity.
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