Role Of Type Ⅰ Interferon Receptor In The Pathogenesis Of Pseudorabies Virus

Pseudorabies virus(PRV)is one of the neurophilic viruses that can infect numerous mammals,including ruminants,carnivores and rodents.Importantly,there is increasing evidence that pseudorabies virus infection is widespread in swine across the world and is a major threat to swine husbandry.However,mechanism underlying interaction between pseudorabies virus and host innate immune system remain to be defined.In this study,we used a mouse model to investigate involvement of interferon α/β(IFN-I)receptor(IFNAR)in pathogenesis of pseudorabies virus.In previous experiments,we found that mice lacking IFNAR were highly susceptible to PRV infection,as evidenced by markedly high mortality rate of infected animals and increased viral replication.In this study,we used PCR,RT-PCR,realtime-PCR,Western-blotting and ELISA.We also prepared the MEFs,in-vitro and in-vivo to study.In this study,we further observed that IFNAR played a key role in antiviral response.Deficiency of IFNAR caused significant increase in replication of PRV.The expression levels of IFN-I in IFNAR-/-mice were lower than WT after the virus infection.The relevant levels of interferon-stimulated genes including IFIT1,IFIT3 and OASL1 in IFNAR knockout mice were low as compared with that of wild-type(WT)after the viral infection.According to these results,it is considered that lack of IFNAR blocks IFN-I-mediated regulation of ISGs.Therefore,the relevant ISGs expression was down-regulated in IFNAR-/-mice infected with PRV.Moreover,IFNAR-/-mice displayed elevated levels of inflammatory cytokines including interleukin 6(IL-6)and IL-1β,and phosphorylation of STAT3 was greatly increased in IFNAR-/-mice after the viral exposure.Together,these data suggested that IFN-I-IFNAR-dependent homeostatic control is critically required for host defense against pseudorabies virus infection.After addition of IFN-β,the expression of IL-1β,IL-6 was down-regulated in the infected mice.These observations confirm that type Ⅰ IFNs play a critical role to control the inflammation due to viral infection.We also used MEFs to study the cellular response(1×104 TCID50)against PRV infection.In-vitro results are consistent with the animal model studies.These findings may provide a useful strategy and idea for the prevention and control of PR.