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
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
复制标题
糖皮质激素诱导的亮氨酸拉链在传染性法氏囊病病毒 (IBDV) 诱导的 I 型干扰素表达抑制和通过与 VP4 相互作用增强宿主细胞中 IBDV 生长中的关键作用
DOI：
10.1128/jvi.02421-12
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发表时间：
2013-01-01
影响因子：
5.4
通讯作者：
Zheng, Shijun J.
中科院分区：
文献类型：
--
作者：
Li, Zhonghua;Wang, Yongqiang;Zheng, Shijun J.
【摘要】：传染性法氏囊病(IBD)是由IBD病毒(IBDV)引起的一种急性、高度传染性、免疫抑制性禽类疾病。尽管 IBDV 诱导的免疫抑制已得到充分证实，但这种诱导的潜在确切分子机制尚不清楚。我们在此报告了通过与宿主细胞中糖皮质激素诱导的亮氨酸拉链（GILZ）相互作用，IBDV VP4被鉴定为干扰素抑制剂。我们发现，在肿瘤坏死因子α（TNF-α）治疗或仙台病毒（SeV）感染后的HEK293T细胞中以及在聚（I·C）刺激后的DF-1细胞中，VP4抑制I型干扰素的表达。此外，VP4诱导的I型干扰素抑制可以通过小干扰RNA（siRNA）敲低GILZ来完全消除。此外，GILZ 的敲低显着抑制了宿主细胞中 IBDV 的生长，并且细胞培养物中的抗 α/β 干扰素抗体可以显着减轻这种抑制（P < 0.001）。因此，VP4 诱导的 I 型干扰素抑制是通过与 GILZ 相互作用介导的，GILZ 是一种似乎抑制细胞对病毒感染反应的蛋白质。
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.