Infectious bursal disease virus protein VP4 suppresses type I interferon expression via inhibiting K48-linked ubiquitylation of glucocorticoid-induced leucine zipper (GILZ)
Infectious bursal disease virus protein VP4 suppresses type I interferon expression via inhibiting K48-linked ubiquitylation of glucocorticoid-induced leucine zipper (GILZ)
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传染性法氏囊病病毒蛋白 VP4 通过抑制糖皮质激素诱导的亮氨酸拉链 (GILZ) 的 K48 泛素化来抑制 I 型干扰素表达
DOI：
10.1016/j.imbio.2017.10.048
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发表时间：
2018-04-01
期刊：
影响因子：
2.8
通讯作者：
Zheng, Shijun J.
中科院分区：
文献类型：
--
作者：
He, Zhiyuan;Chen, Xiang;Zheng, Shijun J.
病毒已经发展出各种方法来逃避宿主的免疫反应。我们以前的研究表明，传染性法氏囊病病毒(IBDV)通过VP4与细胞内糖皮质激素诱导的亮氨酸拉链(GILZ)蛋白相互作用来抑制I型干扰素的产生。然而，确切的潜在分子机制仍不清楚。在本研究中，我们发现IBDV VP4通过抑制K48连接的GILZ泛素化来抑制GILZ的降解。此外，VP4(R41G)突变取消了VP4对干扰素-β表达和GILZ泛素化的抑制作用，表明VP4的41R氨基酸是抑制干扰素-β表达和GILZ泛素化所必需的。此外，IBDV感染或VP4表达显著抑制内源性GILZ泛素化。因此，IBDV VP4通过抑制K48连接的GILZ泛素化抑制I型干扰素的表达，揭示了IBDV抑制宿主应答的新机制。
Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-beta expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-beta expression and GILZ ubiquitylation. Moreover, IBDV infection or VP4 expression markedly inhibited endogenous GILZ ubiquitylation. Thus, IBDV VP4 suppresses type I interferon expression by inhibiting K48 linked ubiquitylation of GILZ, revealing a new mechanism employed by IBDV to suppress host response.