Cai Binxiang, Bai Qingling, Chi Xiaojuan, Goraya Mohsan U, Wang Long, Wang Song, Chen Biao, Chen Ji-Long
Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Front Microbiol. 2017 Dec 19;8:2558. doi: 10.3389/fmicb.2017.02558. eCollection 2017.
Classical swine fever virus (CSFV) commonly infects the lymphatic tissues and immune cells of pigs and could cause a lethal disease in the animals. The process and release of cytokines like type III interferons (IFNs) is one of the important responses of the host innate immunity to viral infection. However, little information is available about type III IFN response to the CSFV infection. In this study, we investigated the expression of type III IFNs including interleukin-28B (IL-28B) and IL-29 in PK-15 cells and pigs following CSFV infection. We found that infection with CSFV was able to induce expression of IL-28B and IL-29 in PK-15 cells, although the increased levels of type III IFNs were limited. Importantly, up-regulation of IL-28B and IL-29 was further observed in CSFV infected animal tissues. The production of IL-28B and IL-29 was reduced by the inactivation of NF-κB in cells, indicating that activated NF-κB is required for efficient expression of type III IFNs induced by CSFV. Moreover, our experiments demonstrated that infection with CSFV strongly stimulated the downstream of STAT1 signaling and . In addition, several critical IFN-stimulated genes (ISGs) including IFITM3, OASL, OAS1, and ISG15 were significantly upregulated at both mRNA and protein levels in PK-15 cells and infected pigs. Together, these results reveal that CSFV can trigger host antiviral immune responses including production of type III IFNs, activation of STAT1, and induction of some critical ISGs.
经典猪瘟病毒（CSFV）通常感染猪的淋巴组织和免疫细胞，并可在动物中引发致命疾病。细胞因子如III型干扰素（IFNs）的产生和释放是宿主先天免疫对病毒感染的重要反应之一。然而，关于III型干扰素对CSFV感染的反应的信息很少。在本研究中，我们调查了CSFV感染后PK-15细胞和猪中包括白细胞介素-28B（IL-28B）和IL-29在内的III型干扰素的表达。我们发现，CSFV感染能够诱导PK-15细胞中IL-28B和IL-29的表达，尽管III型干扰素水平的升高有限。重要的是，在CSFV感染的动物组织中进一步观察到IL-28B和IL-29的上调。细胞中NF-κB的失活降低了IL-28B和IL-29的产生，表明激活的NF-κB是CSFV诱导的III型干扰素有效表达所必需的。此外，我们的实验表明，CSFV感染强烈刺激了STAT1信号的下游。此外，包括IFITM3、OASL、OAS1和ISG15在内的几个关键干扰素刺激基因（ISGs）在PK-15细胞和感染猪的mRNA和蛋白质水平上均显著上调。总之，这些结果表明，CSFV可以触发宿主抗病毒免疫反应，包括III型干扰素的产生、STAT1的激活以及一些关键ISGs的诱导。
