CSFV restricts necroptosis to sustain infection by inducing autophagy/mitophagy-targeted degradation of RIPK3

CSFV 通过诱导自噬/线粒体自噬靶向降解 RIPK3 来限制坏死性凋亡以维持感染

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作者:Keke Wu, Bingke Li, Xiaoai Zhang, Yiqi Fang, Sen Zeng, Wenshuo Hu, Xiaodi Liu, Xueyi Liu, Zhimin Lu, Xiaowen Li, Wenxian Chen, Yuwei Qin, Bolun Zhou, Linke Zou, Feifan Zhao, Lin Yi, Mingqiu Zhao, Shuangqi Fan, Jinding Chen

Abstract

CSFV infection in pigs causes persistent high fever, hemorrhagic necrotizing multi-organ inflammation, and high mortality, which seriously threatens the global swine industry. Cell death is an essential immune response of the host against pathogen invasion, and lymphopenia is the most typical clinical feature in the acute phase of CSFV infection, which affects the initial host antiviral immunity. As an "old" virus, CSFV has evolved mechanisms to evade host immune response after a long genetic evolution. Here, we show that necroptosis is a limiting host factor for CSFV infection and that CSFV-induced autophagy can subvert this host defense mechanism to promote its sustained replication. Our findings reveal a complex link between necroptosis and autophagy in the process of cell death, provide evidence supporting the important role for CSFV in counteracting host cell necrosis, and enrich our knowledge of pathogens that may subvert and evade this host defense.

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