PCBP2 Enhances the Antiviral Activity of IFN-α against HCV by Stabilizing the mRNA of STAT1 and STAT2 英文参考文献.docVIP

PCBP2EnhancestheAntiviralActivityofIFN-aagainst HCVbyStabilizingthemRNAofSTAT1andSTAT2 ZhongshuaiXin1,2,WeiHan1,ZhiqiangZhao1,QingXia3,BinYin1,JiangangYuan1*,XiaozhongPeng1* 1 National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,2 Division of Biochemical and Gene Engineering Medicines, National Institute for Food and Drug Control, Beijing, China,3 National Center of Biomedical Analysis, Beijing, China Abstract Interferon-a (IFN-a) is a natural choice for the treatment of hepatitis C, but half of the chronically infected individuals do not achieve sustained clearance of hepatitis C virus (HCV) during treatment with IFN-a alone. The virus can impair IFN-a signaling and cellular factors that have an effect on the viral life cycles. We found that the protein PCBP2 is down-regulated in HCV-replicon containing cells (R1b). However, the effects and mechanisms of PCBP2 on HCV are unclear. To determine the effect of PCBP2 on HCV, overexpression and knockdown of PCBP2 were performed in R1b cells. Interestingly, we found that PCBP2 can facilitate the antiviral activity of IFN-a against HCV, although the RNA level of HCV was unaffected by either the overexpression or absence of PCBP2 in R1b cells. RIP-qRT-PCR and RNA half-life further revealed that PCBP2 stabilizes the mRNA of STAT1 and STAT2 through binding the 39Untranslated Region (UTR) of these two molecules, which are pivotal for the IFN-a anti-HCV effect. RNA pull-down assay confirmed that there were binding sites located in the C-rich tracts in the 39UTR of their mRNAs. Stabilization of mRNA by PCBP2 leads to the increased protein expression of STAT1 and STAT2 and a consistent increase of phosphorylated STAT1 and STAT2. These effects, in turn, enhance the antiviral effect of IFN-a. These findings indicate t