African swine fever virus cysteine protease pS273R inhibits pyroptosis by noncanonically cleaving gasdermin D.
J Biol Chem
; 298(1): 101480, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34890644
ABSTRACT
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-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Virais
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Proteínas de Ligação a Fosfato
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Febre Suína Africana
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Vírus da Febre Suína Africana
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Proteínas Citotóxicas Formadoras de Poros
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Cisteína Proteases
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China