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

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.

miR-204 suppresses porcine reproductive and respiratory syndrome virus(PRRSV)replication via inhibiting LC3B-mediated autophagy

Porcine reproductive and respiratory syndrome(PRRS)caused by PRRS virus(PRRSV)has been regarded as a persistent challenge for the swine farms worldwide.microRNAs(miRNAs)play key roles in regulating almost every important biological process,including virus-host interaction.In this study,we found that miR-204 was highly expressed in cells that were not permissive to PRRSV infection compared with cells susceptible to PRRSV infection.Subsequently,we demonstrated that overexpression of miR-204 significantly inhibited PRRSV replication in porcine alveolar macrophages(PAMs).Through bioinformatic analysis,we found that there existed a potential binding site of miR-204 on the 30UTR of microtubule associated protein 1 light chain 3B(MAP1LC3B,LC3B),a hallmark of autophagy.Applying experiments including luciferase reporter assay and UV cross-linking and immunoprecipitation(CLIP)assay,we demonstrated that miR-204 directly targeted LC3B,thereby downregulating autophagy.Meanwhile,we investigated the interplay between autophagy and PRRSV replication in PAMs,confirming that PRRSV infection induces autophagy,which in turn facilitates viral replication.Overall,we verify that miR-204 suppresses PRRSV replication via inhibiting LC3B-mediated autophagy in PAMs.These findings will provide a novel potential approach for us to develop antiviral therapeutic agents and controlling measures for future PRRSV outbreaks.

Regulation of antiviral immune response by African swine fever virus(ASFV)

African swine fever(ASF)is a highly contagious and acute hemorrhagic viral disease with a high mortality approaching 100%in domestic pigs.ASF is an endemic in countries in sub-Saharan Africa.Now,it has been spreading to many countries,especially in Asia and Europe.Due to the fact that there is no commercial vaccine available for ASF to provide sustainable prevention,the disease has spread rapidly worldwide and caused great economic losses in swine industry.The knowledge gap of ASF virus(ASFV)pathogenesis and immune evasion is the main factor to limit the development of safe and effective ASF vaccines.Here,we will summarize the molecular mechanisms of how ASFV interferes with the host innate and adaptive immune responses.An in-depth understanding of ASFV immune evasion strategies will provide us with rational design of ASF vaccines.