title: Critical roles of glucocorticoid-induced leucine zipper in infectious bursal disease virus (IBDV)-induced suppression of type I Interferon expression and enhancement of IBDV growth in host cells via interaction with VP4.
abstract: Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced immunosuppression has been well established, the underlying exact molecular mechanism for such induction is not very clear. We report here the identification of IBDV VP4 as an interferon suppressor by interaction with the glucocorticoid-induced leucine zipper (GILZ) in host cells. We found that VP4 suppressed the expression of type I interferon in HEK293T cells after tumor necrosis factor alpha (TNF-α) treatment or Sendai virus (SeV) infection and in DF-1 cells after poly(I·C) stimulation. In addition, the VP4-induced suppression of type I interferon could be completely abolished by knockdown of GILZ by small interfering RNA (siRNA). Furthermore, knockdown of GILZ significantly inhibited IBDV growth in host cells, and this inhibition could be markedly mitigated by anti-alpha/beta interferon antibodies in the cell cultures (P < 0.001). Thus, VP4-induced suppression of type I interferon is mediated by interaction with GILZ, a protein that appears to inhibit cell responses to viral infection.
authors.affiliation: State Key Laboratory of Agrobiotechnology, Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, and College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Li
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Shijun J
authors.initials: SJ
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D007108:Immune Tolerance; D007243:Infectious bursal disease virus / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016350:Leucine Zippers; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D014157:Transcription Factors; C478245:VP4 protein, infectious bursal disease virus; D015678:Viral Structural Proteins