期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-35722-8
关键词
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资金
- Ministry of Science and Technology [MOST 106-2320-B-016-008-, MOST 105-2320-B-016-001-]
- Ministry of National Defense-Medical Affairs Bureau [MAB-107-091]
- National Defense Medical Center [IPM-107-G1-2]
- Taichung Armed Force General Hospital of the Republic of China [107B02]
Grail is a well-characterized mediator of metabolic disease, tumour progression, and immune response. However, its role in influenza A virus (IAV) infection remains poorly understood. In this study, we demonstrated that Grail knockdown potentiates IAV infection, whereas Grail overexpression blocks IAV replication. The intranasal administration of IAV to Grail KO mice led to a lower survival rate than in similarly infected wild-type mice. Additionally, IAV-infected Grail KO mice had higher viral titres, greater immune cell infiltration, and increased expression of inflammatory cytokines in the lungs. Mechanistically, we showed that Grail interacts with viral nucleoprotein (NP), targeting it for degradation and inhibiting IAV replication. NP expression was increased in Grail knockdown cells and reduced in cells overexpressing Grail. Collectively, our results demonstrate that Grail acts as a negative regulator of IAV infection and replication by degrading viral NP. These data increase our understanding of the host antiviral response to infection with IAV.
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