数字农科院2.0

Viral protease binds to nucleosomal DNA and cleaves nuclear cGAS that attenuates type I interferon

文献类型： 外文期刊

作者： Wu, Lei;Yan, Ya;Yuan, Ye;Zhao, Zhenchao;Qu, Weiyu;Huang, Xiangyu;Wang, Haiwei;Li, Pingwei;Li, Xin

作者机构：

关键词： nuclear cGAS;Seneca Valley virus;3C protease;nucleosomal DNA

期刊名称： MBIO

ISSN：

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Nuclear cyclic GMP-AMP synthetase (cGAS) binds to nucleosome with high affinity to prevent its activation by self-DNA. Upon stimulation with double-stranded DNA, cGAS is activated and translocates from the nucleus to the cytoplasm, guided by its N-terminal domain. However, it remains unclear whether viruses can hijack cGAS translocation and regulate its activation. Here, we discovered that the protease 3C of picornavirus Seneca Valley virus (SVV) translocates from the cytoplasm to the nucleus upon viral infection and binds to nuclear DNA. Protease 3C specifically cleaves histone H2A while leaving other histone proteins unaffected. Additionally, DNA binding enhances the protease 3C's ability to cleave nuclear cGAS, leading to its retention in the nucleus. This, in turn, suppresses the induction of type I interferon (IFN-I) follow ing poly(dA:dT) stimulation. These findings reveal a novel mechanism by which a viral protease binds nuclear DNA, cleaves nuclear cGAS and histone H2A, and thereby mislocalizes cGAS, facilitating immune evasion.

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