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

文献类型: 外文期刊

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

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期刊名称: Journal of Biological Chemistry

ISSN: 0021-9258

年卷期: 2022 年 298 卷 1 期

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收录情况: SCIE(2022版) ; EI(2022版)

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 pS273Rcleaved 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-1-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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