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African swine fever virus s273r protein antagonizes type I interferon production by interfering with TBK1 and IrF3 interaction

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Virologica sinica 2023年第6期38卷 911-921页

作者： Hui Li Xiaojie Zheng You Li Yingqi Zhu Yangyang Xu Zilong Yu Wen-Hai Feng state Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijing100193China Frontiers science Center for Molecular Design Breeding College of Biological SciencesChina Agricultural UniversityBeijing100193China Ministry of Agriculture Key Laboratory of soil Microbiology College of Biological SciencesChina Agricultural UniversityBeijing100193China Department of Microbiology and Immunology College of Biological SciencesChina Agricultural UniversityBeijing 100193China

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 affect 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-I production independent of its cysteine protease activity.These findings will help us further understand AsFV pathogenesis.

关键词： African swine fever virus(AsFV) cGAs-sTING s273r IrF3 TBK1 Type I interferon(IFN-I)

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FoxJ1 inhibits African swine fever virus replication and viral s273r protein decreases the expression of FoxJ1 to impair its antiviral effect

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Virologica sinica 2022年第3期37卷 445-454页

作者： Caina Ma shasha Li Fan Yang Weijun Cao Huisheng Liu Tao Feng Keshan Zhang Zixiang Zhu Xiangtao Liu Yonghao Hu Haixue Zheng College of Veterinary Medicine Gansu Agricultural UniversityLanzhou730070China state Key Laboratory of Veterinary Etiological Biology National Foot and Mouth Diseases Reference LaboratoryKey Laboratory of Animal Virology of Ministry of AgricultureLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou730046China

African swine fever(AsF)is a highly pathogenic swine infectious disease that affects domestic pigs and wild boar,which is caused by the African swine fever virus(AsFV).AsF has caused huge economic losses to the pig industry and seriously threatens global food security and livestock health.To date,there is no safe and effective commercial vaccine against AsF.Unveiling the underlying mechanisms of AsFV-host interplay is critical for developing effective vaccines and drugs against AsFV.In the present study,rNA-sequencing,rT-qPCr and Western blotting analysis revealed that the transcriptional and protein levels of the host factor FoxJ1 were significantly down-regulated in primary porcine alveolar macrophages(PAMs)infected by AsFV.rT-qPCr analysis showed that overexpression of FoxJ1 upregulated the transcription of type I interferon and interferon stimulating genes(IsGs)induced by poly(dA:dT).FoxJ1 revealed a function to positively regulate innate immune response,therefore,suppressing the replication of AsFV.In addition,Western blotting analysis indicated that FoxJ1 degraded AsFV MGF505-2r and E165r proteins through autophagy pathway.Meanwhile,rT-qPCr and Western blotting analysis showed that AsFV s273r inhibited the expression of FoxJ1.Altogether,we determined that FoxJ1 plays an antiviral role against AsFV replication,and AsFV protein impairs FoxJ1-mediated antiviral effect by degradation of FoxJ1.Our findings provide new insights into the antiviral function of FoxJ1,which might help design antiviral drugs or vaccines against AsFV infection.

关键词： African swine fever virus(AsFV) FoxJ1 IsGs MGF505-2r E165r s273r

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