Screening Of Immuno-antagonized Viral Proteins Of Highly Pathogenic Virus

The innate immune system plays important roles in protecting the host from pathogenic microbial infection.The pattern recognition receptors(PRRs),such as Toll-like receptors(TLRs),RIG-I-like receptors(RLRs)and NOD-like receptors(NLRs),play anti-pathogenic microorganisms immune response by recognizing pathogen-associated molecular patterns(PAMPs)of pathogenic microorganisms to induce the expression of interferon and inflammatory cytokines.Inflammation is a homeostatic mechanism against pathogenic microorganisms infection that promote the activation of innate immune and adaptive immunity by inducing a series of inflammatory cytokines.Viral infection of the host cells triggers the host’s antiviral innate immune response.In the long processing of evolution,virus evolves a variety of escaping ways against host innate immune response.By escaping the host’s innate immune response,the virus could complete it’s life cycle.In this study,we constructed 32 clones of Lassa fever virus,Ebola virus,Marburg virus,Nipah virus,and Crimea Congo hemorrhage fever virus(CCHFV).Then we screened the effect of these clones on SeV-induced interferon and inflammatory cytokines production,TNFα and IL-1β-induced NF-κB activation,IFNγ-induced JAK-STAT activation and NLRP3 inflammasome activation.In our study,we found that the OTU domain of CCHFV and the P,W and V of Nipah virus and the NP of Lassa fever virus have an negative effect on the activation of IFNβ,ISRE and NF-κB reporter induced by SeV.Differently,The P,W and V of the Nipah virus show an slightly inhibitory effect on activation of interferon and inflammatory cytokines in the q-PCR experiment.Interestingly,The NP of Ebola virus significantly potentiated the transcription of IFNB1 in the q-PCR experiment,while the RNA level of ISGs and inflammatory cytokines was not affected.Through the detection of secretion of extracellular IFNβ,We found that the NP of Ebola virus could potentiated the production of IFNβ in protein level induced by SeV.In addition,the OTU domain of CCHFV and P,W and V of Nipah virus were able to inhibit the activation of IRF1 reporter induced by IFNγ.The C,P and V proteins of Nipah virus were able to inhibit the activation of NF-κB induced by TNFα and IL-1β.The s GP of Ebola virus could enhanced TNFa-induced NF-κB activation but has no significant effect on IL-1β-induced activation of NF-κB.For the activation of NLRP3 inflammasome,The C of the Nipah virus could significantly promoted the maturation of IL-1β.