Anti-TGEV Miller Strain Infection Effect of Lactobacillus plantarum Supernatant Based on the JAK-STAT1 Signaling Pathway

Wang, Kai; Ran, Ling; Yan, Tao; Niu, Zheng; Kan, Zifei; Zhang, Yiling; Yang, Yang; Xie, Luyi; Huang, Shilei; Yu, Qiuhan; Wu, Di; Song, Zhenhui

Recent studies have shown that the main reasons why the body's interferon-beta (IFN-β) cannot fully exert its antiviral effect after TGEV infection are as follows: First, the cells do not respond in time to the immune response because of the level of viral replication and the virus titer of TGEV in the early stage of infection, resulting in lower levels of IFNs, which is the main cause of the short burst of TGEV latency (Zhu et al., 2017) . Second, IFN-β does not play a direct antiviral role. Its antiviral function is produced by activating the IFN-mediated JAK-STAT signaling pathway to stimulate downstream interferonstimulating genes (ISGs) (Saha and Pahan, 2006; Li, 2008; Proia et al., 2011) . And, activation of the JAK-STAT1 signaling pathway requires Phosphorylated STAT1 (Tyr 701) enters the nucleus to activate interferon-stimulating factors ISGs (including MX1, MX2, PKR, OAS, ISG15, and ZAP) (Hovanessian, 1991; Zhu et al., 1997; Shi et al., 2010; Goujon et al., 2013; Amici et al., 2015; Li et al., 2015; Nigg and Pavlovic, 2015) . ZAP can bind viral RNA directly and prevent the accumulation of viral RNA in the cytoplasm. It can also recruit RNA exosomes to degrade target viral RNA (Li et al., 2015) . PKR-mediated inhibition of viral replication is activated by the formation of dsRNA during the replication of single-stranded RNA after viruses invade cells. The main reason is that the amino terminus of PKR can recognize the dsRNA domain and the carboxyl terminus has the kinase domain. When the viral double-stranded RNA is recognized, the inactive PKR protein located in the cytoplasm is phosphorylated. On the other hand, it can also regulate the cell immune response and autophagy caused by virus invasion to inhibit the virus. At the same time, PKR can activate the nuclear factor kappa B (NF-kB) signaling pathway via phosphorylation and further induce IFN production in cells (Sudhakar et al., 2000; Amici et al., 2015) .