Liu Xin, Lai Chengcai, Wang Keyu, Xing Li, Yang Penghui, Duan Qing, Wang Xiliang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; 302 Military Hospital, Beijing, China.
PLoS One. 2015 Apr 24;10(4):e0124651. doi: 10.1371/journal.pone.0124651. eCollection 2015.
Influenza A virus causes annual epidemics and occasional pandemics in humans. Here, we investigated four members of the fibroblast growth factor receptor (FGFR) family; FGFR1 to 4, and examined their expression patterns in human lung epithelial cells A549 with influenza A virus infection. We identified a functional role of FGFR1 in influenza A/Puerto Rico/8/1934 (PR8) and A/Anhui/01/2005 (H5N1) virus replication. Our results showed that FGFR1 silencing by siRNA interference promoted influenza A/PR8 and H5N1 virus replication in A549 cells, while lentivirus-mediated exogenous FGFR1 expression significantly suppressed influenza A virus replication; however, FGFR4 did not have the same effects. Moreover, FGFR1 phosphorylation levels were downregulated in A549 cells by influenza A virus infection, while the repression of FGFR1 kinase using PD173074, a potent and selective FGFR1 inhibitor, could enhance virus replication. Furthermore, we found that FGFR1 inhibits influenza virus internalization, but not binding, during viral entry. These results suggested that FGFR1 specifically antagonizes influenza A virus replication, probably by blocking viral entry.
甲型流感病毒每年都会在人类中引发流行，偶尔还会导致大流行。在此，我们研究了成纤维细胞生长因子受体（FGFR）家族的四个成员，即FGFR1至4，并检测了它们在甲型流感病毒感染的人肺上皮细胞A549中的表达模式。我们确定了FGFR1在甲型流感病毒A/波多黎各/8/1934（PR8）和A/安徽/01/2005（H5N1）复制中的功能作用。我们的结果表明，通过小干扰RNA（siRNA）干扰使FGFR1沉默可促进甲型流感病毒A/PR8和H5N1在A549细胞中的复制，而慢病毒介导的外源性FGFR1表达则显著抑制甲型流感病毒的复制；然而，FGFR4没有相同的作用。此外，甲型流感病毒感染可使A549细胞中FGFR1的磷酸化水平下调，而使用强效选择性FGFR1抑制剂PD173074抑制FGFR1激酶可增强病毒复制。此外，我们发现FGFR1在病毒进入过程中抑制流感病毒内化，但不抑制结合。这些结果表明，FGFR1可能通过阻断病毒进入来特异性拮抗甲型流感病毒的复制。
