Wei Jingyun, Ma Yanmei, Wang Long, Chi Xiaojuan, Yan Ruoxiang, Wang Song, Li Xinxin, Chen Xiaoyong, Shao Wenhan, Chen Ji-Long
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
Vet Microbiol. 2017 May;203:234-244. doi: 10.1016/j.vetmic.2017.03.022. Epub 2017 Mar 18.
Pseudorabies virus, one of the neurotropic viruses, can infect numerous mammals. In particular, pseudorabies virus infection of swine occurs worldwide, and is a major threat to swine industry. However, the mechanism underlying the interaction between pseudorabies virus and host innate immune system is not fully understood. Here, we investigated the involvement of interferon α/β (IFN-α/β) receptor (IFNAR) in the pathogenesis of pseudorabies virus in a mouse model. The results showed that IFNAR-deficient (IFNAR) mice were highly susceptible to the virus infection, as evidenced by markedly reduced survival rate of infected animals and increased viral replication. The expression of IFN-α/β and relevant interferon-stimulated genes in IFNAR mice was significantly lower than that in wild-type (WT) littermates after the viral infection. Moreover, in response to the virus challenge, IFNAR mice displayed elevated levels of inflammatory cytokines including interleukin 6 (IL-6) and IL-1β, and IFNAR cells showed increased phosphorylation of STAT3. Collectively, these data reveal that the IFNAR mice are more sensitive to pseudorabies virus infection than WT animals, and excessive IL-6/STAT3 response in IFNAR mice may contribute to the pathogenesis. Our findings suggest that type I IFNs/IFNAR-dependent homeostatic control of the innate immunity is required for host defense against pseudorabies virus infection.
伪狂犬病病毒是嗜神经病毒之一，可感染多种哺乳动物。特别是，猪伪狂犬病病毒感染在全球范围内发生，对养猪业构成重大威胁。然而，伪狂犬病病毒与宿主先天免疫系统之间相互作用的机制尚未完全阐明。在此，我们在小鼠模型中研究了干扰素α/β（IFN-α/β）受体（IFNAR）在伪狂犬病病毒发病机制中的作用。结果表明，IFNAR缺陷（IFNAR-/-）小鼠对病毒感染高度易感，感染动物的存活率显著降低和病毒复制增加证明了这一点。病毒感染后，IFNAR-/-小鼠中IFN-α/β及相关干扰素刺激基因的表达明显低于野生型（WT）同窝小鼠。此外，在病毒攻击后，IFNAR-/-小鼠表现出包括白细胞介素6（IL-6）和IL-1β在内的炎性细胞因子水平升高，且IFNAR-/-细胞显示STAT3磷酸化增加。总体而言，这些数据表明IFNAR-/-小鼠比WT动物对伪狂犬病病毒感染更敏感，且IFNAR-/-小鼠中过度的IL-6/STAT3反应可能促成发病机制。我们的研究结果表明，I型干扰素/IFNAR依赖的先天免疫稳态控制是宿主抵御伪狂犬病病毒感染所必需的。
