Marek's disease virus protein kinase US3 inhibits DNA-sensing antiviral innate immunity via abrogating activation of NF-κB

文献类型： 外文期刊

第一作者： Li, Kai

作者： Li, Kai;Liu, Rui;Liu, Yongzhen;Gao, Li;Liu, Changjun;Zhang, Yanping;Qi, Xiaole;Cui, Hongyu;Wang, Suyan;Chen, Yuntong;Duan, Yulu;Gao, Yulong;Wang, Xiaomei;Li, Kai;Li, Kai;Wang, Xiaomei

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关键词： Marek's disease virus; US3; innate immunity; DNA sensing; NF-kappa B

期刊名称：MICROBIOLOGY SPECTRUM （ 影响因子：3.8； 五年影响因子：4.1 ）

ISSN：

年卷期： 2025 年 13 卷 4 期

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收录情况： SCI

摘要： Marek's disease virus (MDV) is an avian alphaherpesvirus associated with Marek's disease, an immunosuppressive and lymphoproliferative disease in chickens. The DNA sensing pathway mediates innate immune defense against infection by many DNA-containing pathogens, while viruses have evolved multiple strategies to evade the host immune response to survive in host cells. This study found that ectopic expression of MDV protein kinase US3 inhibited beta interferon (IFN-beta) and interleukin-6 (IL-6) production induced by interferon-stimulatory and viral DNA. US3 was further shown to abolish the nuclear factor kappa B (NF-kappa B) activation. The US3 kinase activity was indispensable for its inhibitory function, as the kinase-dead US3 mutant (US3K220A) did not inhibit NF-kappa B activation. Further studies showed that US3 interacted with the Rel homology domains of the NF-kappa B subunits p65 and p50, which phosphorylated these transcription factors and blocked their nuclear translocation. Finally, US3 deficiency promoted IFN-beta and IL-6 production, resulting in reduced viral replication and lower MDV-specific lesion incidence during MDV infection in chickens. Altogether, these findings reveal a novel mechanism for MDV to evade host antiviral immunity.

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