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

Tembusu virus (TMUV) is a member of the Ntaya virus group within the genus Flavivirus of family Flaviviridae (Yan et al., 2011) . TMUV strains were firstly isolated from mosquitoes in Malaysia and Thailand, but their pathogenicity is not fully understood Pandey et al., 1999) . Sitiawan 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 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), premembrane (PrM/M), and envelope (E)] and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) 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 (90-100%), 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 Liu et al., , 2013 Chen et al., 2013) . The young flocks are more vulnerable to ATMUV infection, characterized by similar 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 easily detected in ovaries and theca folliculi of infected animals, suggesting that the reproductive tissues were the major targets for the viral infection and replication . 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 various cell lines including DEF, CEF, DF-1, BHK-21, Vero, A549, 293T, and HeLa, resulting in a noticeable cytopathic effect (CPE) characterized by cell shrinkage, rounding and detachment (Chen et al., 2016a; .