African swine fever virus pE301R negatively regulates cGAS-STING signaling pathway by inhibiting the nuclear translocation of IRF3.

African swine fever (ASF) is a highly contagious and lethal infectious disease of domestic pigs and wild boars by the African swine fever virus (ASFV). ASFV infects domestic pigs with the mortality rate approaching 100 % at acute stage of infection. The cGAS-STING-mediated antiviral responses are wildly accepted that cGAS acts as DNA sensor for sensing of viral DNA during DNA virus infection. However, the molecular mechanisms underlying negatively regulation of cGAS-STING signaling and type I IFN (IFN-I) production by ASFV proteins are not fully understood. In this study, we demonstrated that ASFV pE301R antagonize the activities of IFN-β-, NF-κB-, ISRE-luciferase (Luc) reporters-induced by cGAS-STING in a dose dependent manner. Consistent with these results, the mRNA levels of Ifnb1, Isg15, Isg56 are attenuated by ASFV pE301R. Furthermore, ASFV pE301R executes its inhibitory function at the downstream of IFN-regulatory factor 3 (IRF3) phosphorylation. Mechanistically, pE301R interacts with IRF3 via its amino acid (aa) 1-200 region, resulting in inhibition of the nuclear translocation of IRF3 induced by cGAMP and poly(dA:dT). Overall, our findings reveal that pE301R acts as a negatively regulator to inhibit IFN-I production and to subvert host antiviral innate immunity during ASFV infection.

Liu X ，Liu H ，Ye G ，Xue M ，Yu H ，Feng C ，Zhou Q ，Liu X ，Zhang L ，Jiao S ，Weng C ，Huang L ... -  《-》

How Does African Swine Fever Virus Evade the cGAS-STING Pathway?

Lin C ，Zhang C ，Chen N ，Meurens F ，Zhu J ，Zheng W ... -  《Pathogens》

Development and characterization of high-efficiency cell-adapted live attenuated vaccine candidate against African swine fever.

Kim MH ，Subasinghe A ，Kim Y ，Kwon HI ，Cho Y ，Chathuranga K ，Cha JW ，Moon JY ，Hong JH ，Kim J ，Lee SC ，Dodantenna N ，Gamage N ，Chathuranga WAG ，Kim Y ，Yoon IJ ，Lee JY ，Mo IP ，Jheong W ，Yoo SS ，Lee JS ... -  《Emerging Microbes & Infections》

Porcine deltacoronavirus nucleocapsid protein antagonizes JAK-STAT signaling pathway by targeting STAT1 through KPNA2 degradation.

Hu Y ，Hao C ，Wang D ，Guo M ，Chu H ，Jin X ，Zu S ，Ding X ，Zhang H ，Hu H ... -  《-》

Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway.

Porcine epidemic diarrhea virus (PEDV) is an entero-pathogenic coronavirus, which belongs to the genus Alphacoronavirus in the family Coronaviridae, causing lethal watery diarrhea in piglets. Previous studies have shown that PEDV has developed an antagonistic mechanism by which it evades the antiviral activities of interferon (IFN), such as the sole accessory protein open reading frame 3 (ORF3) being found to inhibit IFN-β promoter activities, but how this mechanism used by PEDV ORF3 inhibits activation of the type I signaling pathway remains not fully understood. Thus, in this present study, we showed that PEDV ORF3 inhibited both polyinosine-polycytidylic acid (poly(I:C))- and IFNα2b-stimulated transcription of IFN-β and interferon-stimulated genes (ISGs) mRNAs. The expression levels of antiviral proteins in the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated pathway was down-regulated in cells with over-expression of PEDV ORF3 protein, but global protein translation remained unchanged and the association of ORF3 with RLRs-related antiviral proteins was not detected, implying that ORF3 only specifically suppressed the expression of these signaling molecules. At the same time, we also found that the PEDV ORF3 protein inhibited interferon regulatory factor 3 (IRF3) phosphorylation and poly(I:C)-induced nuclear translocation of IRF3, which further supported the evidence that type I IFN production was abrogated by PEDV ORF3 through interfering with RLRs signaling. Furthermore, PEDV ORF3 counteracted transcription of IFN-β and ISGs mRNAs, which were triggered by over-expression of signal proteins in the RLRs-mediated pathway. However, to our surprise, PEDV ORF3 initially induced, but subsequently reduced the transcription of IFN-β and ISGs mRNAs to normal levels. Additionally, mRNA transcriptional levels of signaling molecules located at IFN-β upstream were not inhibited, but elevated by PEDV ORF3 protein. Collectively, these results demonstrate that inhibition of type I interferon signaling by PEDV ORF3 can be realized through down-regulating the expression of signal molecules in the RLRs-mediated pathway, but not via inhibiting their mRNAs transcription. This study points to a new mechanism evolved by PEDV through blockage of the RLRs-mediated pathway by ORF3 protein to circumvent the host's antiviral immunity.

Zheng L ，Liu H ，Tian Z ，Kay M ，Wang H ，Cheng L ，Xia W ，Zhang J ，Wang W ，Cao H ，Xu X ，Gao Z ，Geng R ，Wu Z ，Zhang H ... -  《-》