title: Avian Tembusu virus infection effectively triggers host innate immune response through MDA5 and TLR3-dependent signaling pathways.
abstract: Avian Tembusu virus (ATMUV) is a newly emerged flavivirus that belongs to the Ntaya virus group. ATMUV is a highly pathogenic virus causing significant economic loss to the Chinese poultry industry. However, little is known about the role of host innate immune mechanism in defending against ATMUV infection. In this study, we found that ATMUV infection significantly up-regulated the expression of type I and type III interferons (IFN) and some critical IFN-stimulated genes (ISG) in vivo and in vitro. This innate immune response was induced by genomic RNA of ATMUV. Furthermore, we observed that ATMUV infection triggered IFN response mainly through MDA5 and TLR3-dependent signaling pathways. Strikingly, shRNA-based disruption of IPS-1, IRF3 or IRF7 expression significantly reduced the production of IFN in the 293T cell model. Moreover, NF-κB was shown to be activated in both chicken and human cells during the ATMUV infection. Inhibition of NF-κB signaling also resulted in a clear decrease in expression of IFN. Importantly, experiments revealed that treatment with IFN significantly impaired ATMUV replication in the chicken cell. Consistently, type I IFN also exhibited promising antiviral activity against ATMUV replication in the human cell. Together, these data indicate that ATMUV infection triggers host innate immune response through MDA5 and TLR3-dependent signaling that controls IFN production, and thereby induces an effective antiviral immunity.
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.|College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.|Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agriculture Sciences, Fuzhou, 350002, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Guifeng
authors.initials: G
authors.lastname: Luo
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Shuncheng
authors.initials: S
authors.lastname: Lin
authors.affiliation: Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agriculture Sciences, Fuzhou, 350002, China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Mohsan Ullah
authors.initials: MU
authors.lastname: Goraya
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chi
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Xiancheng
authors.initials: X
authors.lastname: Zeng
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. chenjl@im.ac.cn.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China. chenjl@im.ac.cn.
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Chen
mesh_terms: D000818:Animals; D002642:Chick Embryo / Q000821:virology; D002645:Chickens / Q000276:immunology / Q000821:virology; D005416:Flavivirus / Q000276:immunology*; D018177:Flavivirus Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D007113:Immunity, Innate / Q000276:immunology; D000072640:Interferon-Induced Helicase, IFIH1 / Q000502:physiology*; D007372:Interferons / Q000502:physiology; D011201:Poultry Diseases / Q000276:immunology / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D015398:Signal Transduction / Q000276:immunology*; D051196:Toll-Like Receptor 3 / Q000502:physiology*
chemical_list: D012367:RNA, Viral; D051196:Toll-Like Receptor 3; D007372:Interferons; D000072640:Interferon-Induced Helicase, IFIH1