Abstract
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.
基金项目
National Natural Science Foundation of China,China(32172869)