All authors read and approved the final manuscript. Funding This study was supported by Natural Science Foundation of China (U1405216), the National Basic Research Program (973) of China (2015CB910502), National Key Research and Development Program of China (2016YFD0500205), and Intramural grant of Fujian Agriculture and Forestry University. Conflict of interest statement The authors declare that the research was conducted in the absence of any Apigenin commercial or financial relationships that could be construed as a potential conflict of interest. Supplementary material The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb.2017.00672/full#supplementary-material Click here for additional data file.(345K, TIF) Click here for additional data file.(580K, TIF) Click here for additional data file.(574K, TIF) Click here for additional data file.(323K, TIF) Click here for additional data file.(307K, TIF) Click here for additional data file.(413K, TIF). ATMUV replication in DF-1 cells. However, disruption of IFITM2 expression had no obvious effect on the ATMUV replication. In addition, overexpression of chicken or duck IFITM1 and IFITM3 in DF-1 cells impaired the Apigenin replication of ATMUV. Taken together, these results reveal that induced expression of avian IFITM1 and IFITM3 in response to ATMUV contamination can effectively restrict the computer virus replication, and suggest that increasing IFITM proteins in host may be a useful strategy for control of ATMUV contamination. of family (Yan et al., 2011). TMUV strains were firstly isolated from mosquitoes in Malaysia and Thailand, but their pathogenicity is not fully comprehended (Platt et al., 1975; Pandey et al., 1999). Sitiawan computer virus, a broiler-origin TMUV strain, was the first pathogenic virus causing encephalitis and retarded growth in broiler chicks (Kono et al., 2000). Since 2009, Chinese domestic poultry including ducks, chickens, and geese have been manifesting a new epidemic disease caused by a TMUV-related flavivirus, named as avian Tembusu computer virus (ATMUV). This outbreak was quickly spread to many provinces of China and several south-eastern Asian countries (Homonnay et al., 2014; Thontiravong et al., 2015). ATMUV genome consists of a single strand positive-sense RNA and encodes three structural proteins [capsid (C), pre-membrane (PrM/M), and envelope (E)] and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) (Liu et al., 2013; Homonnay et al., 2014). ATMUV-infected adult animals showed symptoms of hemorrhagic ovaritis and acute egg drop syndrome, high fever, anorexia, diarrhea, ataxia, weight loss and paralysis, with a high morbidity (90C100%), and mortality ranged from 0 to 30% depending on different management and weather conditions, leading to enormous economic losses to poultry industry in China (Cao et al., 2011; Su et al., 2011; Yan et al., 2011; Liu et al., 2012, 2013; Chen et al., 2013). The young flocks are more vulnerable to ATMUV contamination, characterized by comparable clinical symptoms including anorexia, diarrhea, high fever and severe neurologic dysfunction, with a higher mortality than adult birds (Vaidya et al., 2012; Ti et al., 2015). ATMUV was very Apigenin easily detected in ovaries and theca folliculi of infected animals, suggesting that this reproductive tissues were the major targets for the viral contamination and replication (Liu et al., 2012). Viral RNA was also detected in spleen, trachea, kidney, brain, and blood of infected host (Yan et al., 2011; Liu et al., 2012). In addition, it was observed that ATMUV could infect numerous cell lines including DEF, CEF, DF-1, BHK-21, Vero, A549, 293T, PTGER2 and HeLa, resulting in a apparent cytopathic effect (CPE) characterized by cell shrinkage, rounding and detachment (Chen et al., 2016a; Wang H. J. et al., 2016). It has been reported that ATMUV RNA and neutralizing antibodies was detected in duck farm workers in Shandong province of China (Tang et al., 2013), suggesting that this computer virus could infect human. But a disease associated with ATMUV contamination has not been found in human. Moreover, it was shown that ATMUV failed to cause any clinical manifestation or viremia in non-human primates, indicating that ATMUV is usually unlikely to emerge as a human pathogen for the time being (Wang H. J. et al., 2016). However, due to zoonotic nature of its genus Flavivirus relatives, ATMUV might be a potential threat to human health in the Apigenin future (Bowen et al., 1975; Apigenin Liu et al., 2013). Host innate immune response serves as the first line of defense against the infection of pathogens at the early stages. Innate immune system recognizes viruses invasion via specific pattern acknowledgement receptors (PRRs) to sense pathogen associated molecular patterns (PAMPs) expressed by viruses. Activated PRRs then interact with adaptor.