African swine fever virus protein MGF-505-7R promotes virulence and pathogenesis by inhibiting JAK1-and JAK2-mediated signaling

文献类型： 外文期刊

第一作者： Li, Dan

作者： Li, Dan;Zhang, Jing;Yang, Wenping;Li, Pan;Ru, Yi;Kang, Weifang;Li, LuLu;Zheng, Haixue;Li, Dan;Zhang, Jing;Yang, Wenping;Li, Pan;Ru, Yi;Kang, Weifang;Li, LuLu;Zheng, Haixue;Ran, Yong

作者机构：

期刊名称：JOURNAL OF BIOLOGICAL CHEMISTRY （ 影响因子：5.486； 五年影响因子：5.295 ）

ISSN：

年卷期： 2021 年 297 卷 5 期

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收录情况： SCI

摘要： African swine fever virus (ASFV) is a large DNA virus that is highly contagious and pathogenic in domestic pigs with a mortality rate up to 100%. However, how ASFV suppresses JAK-STAT1 signaling to evade the immune response remains unclear. In this study, we found that the ASFV-encoded protein MGF-505-7R inhibited proinflammatory IFN-gamma-mediated JAK-STAT1 signaling. Mechanistically, MGF-505-7R was found to interact with JAK1 and JAK2 and mediate their degradation. Further study indicated that MGF-505-7R promoted degradation of JAK1 and JAK2 by upregulating the E3 ubiquitin ligase RNF125 expression and inhibiting expression of Hes5, respectively. Consistently, MGF-505-7R-deficient ASFV induced high levels of IRF1 expression and displayed compromised replication both in primary porcine alveolar macrophages and pigs compared with wild-type ASFV. Furthermore, MGF-505-7R deficiency attenuated the virulence of the ASFV and pathogenesis of ASF in pigs. These findings suggest that the JAK-STAT1 axis mediates the innate immune response to the ASFV and that MGF-505-7R plays a critical role in the virulence of the ASFV and pathogenesis of ASF by antagonizing this axis. Thus, we conclude that deletion of MGF-505-7R may serve as a strategy to develop attenuated vaccines against the ASFV.

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