African swine fever virus cysteine protease pS273R inhibits pyroptosis by noncanonically cleaving gasdermin D

文献类型： 外文期刊

第一作者： Zhao, Gaihong

作者： Zhao, Gaihong;Li, Tingting;Liu, Xuemin;Zhang, Taoqing;Zhang, Zhaoxia;Kang, Li;Song, Jie;Zhou, Shijun;Chen, Xin;Wang, Xiao;Li, Jiangnan;Huang, Li;Li, Changyao;Bu, Zhigao;Zheng, Jun;Weng, Changjiang

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： 2022 年 298 卷 1 期

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收录情况： SCI

摘要： African swine fever (ASF) is a viral hemorrhagic disease that affects domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). The ASFV virion contains a long double-stranded DNA genome, which encodes more than 150 proteins. However, the immune escape mechanism and pathogenesis of ASFV remain poorly understood. Here, we report that the pyroptosis execution protein gasdermin D (GSDMD) is a new binding partner of ASFV-encoded protein S273R (pS273R), which belongs to the SUMO-1 cysteine protease family. Further experiments demonstrated that ASFV pS273R-cleaved swine GSDMD in a manner dependent on its protease activity. ASFV pS273R specifically cleaved GSDMD at G107-A108 to produce a shorter N-terminal fragment of GSDMD consisting of residues 1 to 107 (GSDMD-N1-107). Interestingly, unlike the effect of GSDMD-N1-279 fragment produced by caspase-l-mediated cleavage, the assay of LDH release, cell viability, and virus replication showed that GSDMD-N1-107 did not trigger pyroptosis or inhibit ASFV replication. Our findings reveal a previously unrecognized mechanism involved in the inhibition of ASFV infection-induced pyroptosis, which highlights an important function of pS273R in inflammatory responses and ASFV replication.

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