Influenza A viruses balance ER stress with host protein synthesis shutoff.

Details

Serval ID
serval:BIB_E216ED6F6864
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Influenza A viruses balance ER stress with host protein synthesis shutoff.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Mazel-Sanchez B., Iwaszkiewicz J., Bonifacio JPP, Silva F., Niu C., Strohmeier S., Eletto D., Krammer F., Tan G., Zoete V., Hale B.G., Schmolke M.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
07/09/2021
Peer-reviewed
Oui
Volume
118
Number
36
Pages
e2024681118
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
A549 Cells, Endoplasmic Reticulum/metabolism, Endoplasmic Reticulum Stress/physiology, HEK293 Cells, Host-Pathogen Interactions/physiology, Humans, Influenza A virus/genetics, Influenza A virus/metabolism, Influenza A virus/pathogenicity, Neuraminidase/metabolism, Unfolded Protein Response/genetics, Unfolded Protein Response/physiology, Viral Nonstructural Proteins/genetics, Virus Replication/genetics, CPSF30, ER stress, NS1, influenza virus, neuraminidase
Pubmed
Create date
04/10/2021 13:43
Last modification date
22/01/2022 7:32
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