NF90 Exerts Antiviral Activity through Regulation of PKR Phosphorylation and Stress Granules in Infected Cells

CORC > 厦门大学 > 生命科学－已发表论文

	NF90 Exerts Antiviral Activity through Regulation of PKR Phosphorylation and Stress Granules in Infected Cells
	Wen, Xi ; Huang, Xiaofeng ; Mok, Bobo Wing-Yee ; Chen, Yixin ; Zheng, Min ; Lau, Siu-Ying ; Wang, Pui ; Song, Wenjun ; Jin, Dong-Yan ; Yuen, Kwok-Yung ; Chen, Honglin ; Chen YX(陈毅歆) ; Chen HL(陈鸿霖)
刊名	http://dx.doi.org/10.4049/jimmunol.1302813
	2014-04-15
关键词	DOUBLE-STRANDED-RNA INFLUENZA-A VIRUS DEPENDENT PROTEIN-KINASE ADENOSINE-DEAMINASE ADAR1 RIBOSOME ENTRY SITE ACTIVATED T-CELLS NS1 PROTEIN BINDING-PROTEIN TRANSLATIONAL CONTROL INHIBITS TRANSLATION
英文摘要	Council of the Hong Kong Special Administrative Region [7620/10M, 7629/13M]; Areas of Excellence Scheme of the University Grants Committee [AoE/M-12/06]; NF90 was shown to exhibit broad antiviral activity against several viruses, but detailed mechanisms remain unclear. In this study, we examined the molecular basis for the inhibitory effect of NF90 on virus replication mediated through protein kinase (PKR)-associated translational regulation. We first verified the interaction between NF90 and PKR in mammalian cells and showed that NF90 interacts with PKR through its C-terminal and that the interaction is independent of NF90 RNA-binding properties. We further showed that knockdown of NF90 resulted in significantly lower levels of PKR phosphorylation in response to dsRNA induction and influenza virus infection. We also showed that high concentrations of NF90 exhibit negative regulatory effects on PKR phosphorylation, presumably through competition for dsRNA via the C-terminal RNA-binding domain. PKR activation is essential for the formation of stress granules in response to dsRNA induction. Our results showed that NF90 is a component of stress granules. In NF90-knockdown cells, dsRNA treatment induced significantly lower levels of stress granules than in control cells. Further evidence for an NF90-PKR antiviral pathway was obtained using an NS1 mutated influenza A virus specifically attenuated in its ability to inhibit PKR activation. This mutant virus replicated indistinguishably from wild-type virus in NF90-knockdown cells, but not in scrambled control cells or Vero cells, indicating that NF90's antiviral function occurs through interaction with PKR. Taken together, these results reveal a yet-to-be defined host antiviral mechanism in which NF90 upregulation of PKR phosphorylation restricts virus infection.
语种	英语
出版者	AMER ASSOC IMMUNOLOGISTS
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90795]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Wen, Xi,Huang, Xiaofeng,Mok, Bobo Wing-Yee,et al. NF90 Exerts Antiviral Activity through Regulation of PKR Phosphorylation and Stress Granules in Infected Cells[J]. http://dx.doi.org/10.4049/jimmunol.1302813,2014.
APA	Wen, Xi.,Huang, Xiaofeng.,Mok, Bobo Wing-Yee.,Chen, Yixin.,Zheng, Min.,...&陈鸿霖.(2014).NF90 Exerts Antiviral Activity through Regulation of PKR Phosphorylation and Stress Granules in Infected Cells.http://dx.doi.org/10.4049/jimmunol.1302813.
MLA	Wen, Xi,et al."NF90 Exerts Antiviral Activity through Regulation of PKR Phosphorylation and Stress Granules in Infected Cells".http://dx.doi.org/10.4049/jimmunol.1302813 (2014).