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Cellular DDX21 RNA helicase inhibits influenza A virus replication but is counteracted by the viral NS1 protein.

Authors
  • Chen, Guifang1
  • Liu, Chien-Hung1
  • Zhou, Ligang1
  • Krug, Robert M2
  • 1 Department of Molecular Biosciences, Center of Infectious Disease, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
  • 2 Department of Molecular Biosciences, Center of Infectious Disease, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell host & microbe
Publication Date
Apr 09, 2014
Volume
15
Issue
4
Pages
484–493
Identifiers
DOI: 10.1016/j.chom.2014.03.002
PMID: 24721576
Source
Medline
License
Unknown

Abstract

Influenza A virus RNA synthesis is catalyzed by the viral polymerase comprised of the PA, PB1, and PB2 proteins. We show that the host DDX21 RNA helicase restricts influenza A virus by binding PB1 and inhibiting polymerase assembly, resulting in reduced viral RNA and protein synthesis. Later during infection, the viral NS1 protein overcomes this restriction by binding to DDX21 and displacing PB1. DDX21 binds to a region of the NS1 N-terminal domain that also participates in other critical functions. A virus mutant whose NS1 protein is unable to bind DDX21 exhibits reduced viral protein synthesis at both late and early times of infection, a phenotype converted to wild-type upon DDX21 knockdown. As sequential interaction of PB1 and NS1 with DDX21 leads to temporal regulation of viral gene expression, influenza A virus likely uses the DDX21-NS1 interaction not only to overcome restriction, but also to regulate the viral life cycle.

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