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Title

Influenza A viruses balance ER stress with host protein synthesis shutoff

Authors
Iwaszkiewicz, Justyna
Strohmeier, Shirin
Eletto, Davide
Krammer, Florian
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Published in Proceedings of the National Academy of Sciences. 2021, vol. 118, no. 36, e2024681118
Abstract 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.
Identifiers
PMID: 34479996
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Structures
Research group Modulation de la flore microbienne dans un hôte infecté par un virus (947)
Project FNS: 182475
Citation
(ISO format)
MAZEL-SANCHEZ, Beryl et al. Influenza A viruses balance ER stress with host protein synthesis shutoff. In: Proceedings of the National Academy of Sciences, 2021, vol. 118, n° 36, p. e2024681118. doi: 10.1073/pnas.2024681118 https://archive-ouverte.unige.ch/unige:154639

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Deposited on : 2021-09-15

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