title: Eukaryotic translational initiation factor 4AII reduces the replication of infectious bursal disease virus by inhibiting VP1 polymerase activity.
abstract: Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although an interaction between eukaryotic translational initiation factor 4AII (eIF4AII) of the host and viral protein 1 (VP1), the RNA-dependent RNA polymerase (RdRp) of IBDV, has been established, the underlying effects of this interaction on IBDV and the molecular mechanism remain unclear. We here report that interaction of the host eIF4AII with VP1 inhibits the RNA polymerase activity of IBDV to reduce its replication in host cells. We found that ectopically expressed eIF4AII markedly inhibited IBDV growth in DF1 cells, and knockdown of eIF4AII by small interfering RNA significantly enhanced viral replication in CEF cells. Furthermore, IBDV infection led to an increase in host eIF4AII expression, suggesting a feedback mechanism between the host and virus infection both in vitro and in vivo, which further confirmed the involvement of the host eIF4AII in the IBDV life cycle. Thus, via the interaction with VP1, eIF4AII plays a critical role in the IBDV life cycle, by inhibiting viral RNA polymerase activity, leading to a reduction of IBDV replication in cells.
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Lizhou
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Qi
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin 150069, PR China. Electronic address: xmw@hvri.ac.cn.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D039601:Eukaryotic Initiation Factor-4A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D007243:Infectious bursal disease virus / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D034741:RNA, Small Interfering; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D014709:Vero Cells; D015678:Viral Structural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; C107669:VP1 protein, infectious bursal disease virus; D015678:Viral Structural Proteins; D039601:Eukaryotic Initiation Factor-4A; D012324:RNA-Dependent RNA Polymerase
keywords: Eukaryotic translational initiation factor 4AII; Infectious bursal disease virus; RNA polymerase activity; Viral protein 1; Viral replication