Avian Interferon-Inducible Transmembrane Protein Family Effectively Restricts Avian Tembusu Virus Infection

Chen, Shilong; Wang, Long; Chen, Jieying; Zhang, Lanlan; Wang, Song; Goraya, Mohsan U.; Chi, Xiaojuan; Na, Yang; Shao, Wenhan; Yang, Zhou; Zeng, Xiancheng; Chen, Shaoying; Chen, Ji-Long

IFITMs serve as critical effector molecules in host innate immune system and effectively restrict a wide range of pathogenic viruses, such as dengue virus, influenza A virus, Hepatitis C Virus, West Nile Virus, and HIV-1 (Brass et al., 2009; Wilkins et al., 2013; Yu et al., 2015) . In order to survive, some viruses such as arenavirus and foot-and-mouth disease virus have evolved multiple strategies to evade the antiviral effects of IFITMs (Bailey et al., 2014; Zhang et al., 2016) . Furthermore, human cytomegalovirus could exploit IFITMs to facilitate morphogenesis of virion assembly compartment (Xie et al., 2014) . To investigate the role of IFITM proteins in restricting ATMUV replication, we generated DF-1 cell lines stably disrupting chicken IFITM1, IFITM2, or IFITM3 expression. Indeed, disruption of endogenous IFITM1 and IFITM3 by shRNA greatly enhanced ATMUV infection. Furthermore, ectopic expression of chicken and duck IFITM1 or IFITM3 markedly inhibited ATMUV replication. Interestingly, chIFITM2 was significantly upregulated after ATMUV infection in vitro, but we found that altering IFITM2 expression had mild effect on ATMUV infection. A previous report showed that duck IFITM1 was greatly upregulated after highly pathogenic IAV infection but its antiviral activity was low in vitro (Blyth et al., 2015) . The differences in viral entry mechanisms of IAV and ATMUV in the different types of host cells may account for the differential antiviral activity of IFITM proteins.