刺
干扰素
Ⅰ型干扰素
HDAC6型
病毒学
生物
化学
免疫学
遗传学
基因
物理
组蛋白
组蛋白脱乙酰基酶
热力学
作者
Qiongzhen Zeng,Zixin Chen,Shan Li,Huang Zi-wei,Zhe Ren,Cuifang Ye,Xiao Wang,Jun Zhou,Kaisheng Liu,Kai Zheng,Yifei Wang
标识
DOI:10.1038/s44319-024-00358-5
摘要
Histone deacetylase HDAC6 has been implicated in regulating antiviral innate immunity. However, its precise function in response to DNA virus infection remains elusive. Herein, we find that HDAC6 deficiency promotes the activation of cGAS-STING signaling and type I interferon (IFN) production, both in vitro and in vivo, resulting in a decrease in HSV-1 infection. Mechanistically, HDAC6 deacetylates tripartite motif protein 56 (TRIM56) at K110 in mice, thereby impairing the monoubiquitination cGAS and its DNA binding ability. Overexpression of TRIM56 K110Q protects mice against HSV-1 infection. Notably, different amino acids at position 110 of TRIM56 in human and mouse cause species-specific IFN responses. Further, we show that during early stages of HSV-1 infection, the viral protein US3 phosphorylates HDAC6 to inhibit the cGAS-mediated antiviral response. Our results suggest that HDAC6 inhibits cGAS activation through TRIM56 deacetylation in a species-specific manner.
科研通智能强力驱动
Strongly Powered by AbleSci AI