首页|African swine fever virus S273R protein antagonizes type Ⅰ interferon production by interfering with TBK1 and IRF3 interaction

African swine fever virus S273R protein antagonizes type Ⅰ interferon production by interfering with TBK1 and IRF3 interaction

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African swine fever(ASF)is originally reported in East Africa as an acute hemorrhagic fever.African swine fever virus(ASFV)is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response.S273R protein(pS273R),as a SUMO-1 specific cysteine protease,can afect viral packaging by cutting polymeric proteins.In this study,we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type Ⅰ interferon(IFN-Ⅰ)production.A detailed analysis showed that pS273R inhibited IFN-Ⅰ production by interacting with interferon regulatory factor 3(IRF3).Subsequently,we showed that pS273R disrupted the association between TBK1 and IRF3,leading to the repressed IRF3 phosphorylation and dimerization.Deletion and point mutation analysis verified that pS273R impaired IFN-Ⅰproduction independent of its cysteine protease activity.These findings will help us further understand ASFV pathogenesis.

African swine fever virus(ASFV)cGAS-STINGS273RIRF3TBK1Type Ⅰ interferon(IFN-Ⅰ)

Hui Li、Xiaojie Zheng、You Li、Yingqi Zhu、Yangyang Xu、Zilong Yu、Wen-Hai Feng

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State Key Laboratory of Agrobiotechnology,College of Biological Sciences,China Agricultural University,Beijing,100193,China

Frontiers Science Center for Molecular Design Breeding,College of Biological Sciences,China Agricultural University,Beijing,100193,China

Ministry of Agriculture Key Laboratory of Soil Microbiology,College of Biological Sciences,China Agricultural University,Beijing,100193,China

Department of Microbiology and Immunology,College of Biological Sciences,China Agricultural University,Beijin

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National Natural Science Foundation of China,China

32172869

2023

10.1016/j.virs.2023.08.009

中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
年,卷(期)：2023.38(6)
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