期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 298, 期 1, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jbc.2021.101480
关键词
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资金
- National Natural Science Foundation of China [31941002, 32172874]
- National Key Research and Development Program of China [2021YFD1800100]
- State Key Laboratory of Veterinary Biotechnology Program [SKLVBP202101]
Research has found that the pyroptosis execution protein gasdermin D (GSDMD) is a new binding partner of ASFV-encoded protein S273R (pS273R). Further experiments showed that pS273R can cleave swine GSDMD, producing a shorter N-terminal fragment that does not trigger pyroptosis or inhibit ASFV replication. This discovery reveals a previously unrecognized mechanism involved in the inhibition of pyroptosis induced by ASFV infection.
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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