title: Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions.
abstract: Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China; Shandong Binzhou Animal Science and Veterinary Medicine Institute, 169 Yellow River Road 2, Binzhou, Shandong Province 256600, China. Electronic address: lc_0625@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Ge
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Peng-peng
authors.initials: PP
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shandong Lvdu Ante Veterinary Drug Industry, 169 Yellow River Road 2, Binzhou, Shandong Province 256600, China.
authors.forename: Juan-juan
authors.initials: JJ
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Ming-xia
authors.initials: MX
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Shandong Binzhou Animal Science and Veterinary Medicine Institute, 169 Yellow River Road 2, Binzhou, Shandong Province 256600, China.
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Shen
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Hu
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ishag
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, Jiangsu Province 210095, China. Electronic address: xmao@njau.edu.cn.
authors.forename: Xiang
authors.initials: X
authors.lastname: Mao
mesh_terms: D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000502:physiology*; D004672:Encephalitis, Japanese / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D020506:Untranslated Regions; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D020506:Untranslated Regions; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases
keywords: DEAD box RNA helicase DDX3; Japanese encephalitis virus; Un-translation region; Viral non-structural protein