Journal
FEBS LETTERS
Volume 590, Issue 16, Pages 2797-2810Publisher
WILEY-BLACKWELL
DOI: 10.1002/1873-3468.12311
Keywords
influenza A virus; NF90; nonstructural protein 1; protein kinase R phosphorylation; stress granules
Funding
- Basic Research Expenditure from Chinese Academy of Inspection and Quarantine [2014JK007]
- National Natural Science Foundation of China [31470239]
- Beijing Natural Science Foundation [6152020]
- National Science & Technology Pillar Program during the Twelfth Five-Year Plan Period from the Ministry of Science and Technology of China [2013BAD12B01]
- National Basic Research Program of China (973 Programs) [2011CB504704-X]
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NF90 is a novel host antiviral factor that regulates PKR activation and stress granule formation in influenza A virus (IAV)-infected cells, but the precise mechanisms by which it operates remain unclear. We identified NF90 as a novel interacting protein of IAV nonstructural protein 1 (NS1). The interaction was dependent on the RNA-binding properties of NS1. NS1 associated with NF90 and PKR simultaneously; however, the interaction between NF90 and PKR was restricted by NS1. Knockdown of NF90 promoted inhibition of PKR phosphorylation induced by NS1, while coexpression of NF90 impeded reduction of PKR phosphorylation and stress granule formation triggered by NS1. In summary, NF90 exerts its antiviral activity by antagonizing the inhibitory role of NS1 on PKR phosphorylation.
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