Swine enteric viruses are a major cause of piglet diarrhea, causing a devastating impact on the pork industry. To further understand the molecular epidemiology and evolutionary diversity of swine enteric viruses, we carried out a molecular epidemiological investigation of swine enteric viruses (PEDV, PDCoV, PoRVA, and TGEV) on 7107 samples collected from pig farms in south-central China. The results demonstrated that PEDV is the predominant pathogen causing piglet diarrhea, and its infection occurs mainly in relatively cold winter and spring in Hunan and Hubei provinces. The positive rate of PEDV showed an abnormal increase from 2020 to 2021, and that of PoRVA and PDCoV exhibited gradual increases from 2018 to 2021. PEDV-PoRVA and PEDV-PDCoV were the dominant co-infection modes. A genetic evolution analysis based on the PEDV S1 gene and ORF3 gene revealed that the PEDV GII-a is currently epidemic genotype, and the ORF3 gene of DY2020 belongs to a different clade relative to other GII-a strains isolated in this study. Overall, our results indicated that the variant PEDV GII-a is the main pathogen of piglet diarrhea with a trend of outbreak. G9 is the dominant PoRVA genotype and has the possibility of outbreak as well. It is therefore critical to strengthen the surveillance of PEDV and PoRVA, and to provide technical reserves for the prevention and control of piglet diarrhea.

Japanese encephalitis virus (JEV) infection causes host endoplasmic reticulum stress (ERS) reaction, and then induces cell apoptosis through the UPR pathway, invading the central nervous system and causing an inflammation storm. The endoplasmic reticulum stress inhibitor, 4-phenyl-butyric acid (4-PBA), has an inhibitory effect on the replication of flavivirus. Here, we studied the effect of 4-PBA on JEV infection both in vitro and vivo. The results showed that 4-PBA treatment could significantly decrease the titer of JEV, inhibit the expression of the JEV NS3 protein (in vitro, p < 0.01) and reduce the positive rate of the JEV E protein (in vivo, p < 0.001). Compared to the control group, 4-PBA treatment can restore the weight of JEV-infected mice, decrease the level of IL-1β in serum and alleviate the abnormalities in brain tissue structure. Endoplasmic reticulum stress test found that the expression level of GRP78 was much lower and activation levels of PERK and IRE1 pathways were reduced in the 4-PBA treatment group. Furthermore, 4-PBA inhibited the UPR pathway activated by NS3, NS4b and NS5 RdRp. The above results indicated that 4-PBA could block JEV replication and inhibit ER stress caused by JEV. Interestingly, 4-PBA could reduce the expression of NS5 by inhibiting transcription (p < 0.001), but had no effect on the expression of NS3 and NS4b. This result may indicate that 4-PBA has antiviral activity independent of the UPR pathway. In summary, the effect of 4-PBA on JEV infection is related to the inhibition of ER stress, and it may be a promising drug for the treatment of Japanese encephalitis.

The porcine reproductive and respiratory syndrome virus (PRRSV) causes a highly contagious disease in domestic swine. Signaling lymphocytic activation molecule family member 1 (SLAMF1) is a costimulatory factor that is involved in innate immunity, inflammation, and infection. Here, we demonstrate that overexpression of the SLAMF1 gene inhibited PRRSV replication significantly and reduced the levels of key signaling pathways, including MyD88, RIG-I, TLR2, TRIF, and inflammatory factors IL-6, IL-1β, IL-8, TNF-β, TNF-α, and IFN-α in vitro. However, the knockdown of the SLAMF1 gene could enhance replication of the PRRSV and the levels of key signaling pathways and inflammatory factors. Overall, our results identify a new, to our knowledge, antagonist of the PRRSV, as well as a novel antagonistic mechanism evolved by inhibiting innate immunity and inflammation, providing a new reference and direction for PRRSV disease resistance breeding.