Seneca Valley Virus (SVV), a member of the Picornaviridae family, is an emerging porcine virus that can cause vesicular disease in pigs. However, the immune evasion mechanism of SVV remains unclear, as does its interaction with other pathways. STING (Stimulator of interferon genes) is typically recognized as a critical factor in innate immune responses to DNA virus infection, but its role during SVV infection remains poorly understood. In the present study, we observed that STING was degraded in SVV-infected PK-15 cells, and SVV replication in the cells was affected when STING was knockdown or overexpressed. The STING degradation observed was blocked when the SVV-induced autophagy was inhibited by using autophagy inhibitors (Chloroquine, Bafilomycin A1) or knockdown of autophagy related gene 5 (ATG5), suggesting that SVV-induced autophagy is responsible for STING degradation. Furthermore, the STING degradation was inhibited when reticulophagy regulator 1 (FAM134B), a reticulophagy related receptor, was knocked down, indicating that SVV infection induces STING degradation via reticulophagy. Further study showed that in eukaryotic translation initiation factor 2 alpha kinase 3 (PERK)/activating transcription factor 6 (ATF6) deficient cells, SVV infection failed to induce reticulophagy-medaited STING degradation, indicating that SVV infection caused STING degradation via PERK/ATF6-mediated reticulophagy. Notably, blocking reticulophagy effectively hindered SVV replication. Overall, our study suggested that SVV infection resulted in STING degradation via PERK and ATF6-mediated reticulophagy, which may be an immune escape strategy of SVV. This finding improves the understanding of the intricate interplay between viruses and their hosts and provides a novel strategy for the development of novel antiviral drugs.

Foot-and-mouth disease (FMD) is an acute contagious disease of cloven-hoofed animals such as cattle, pigs, and sheep. Current emergency FMD vaccines are of limited use for early protection because their protective effect starts 7 days after vaccination. Therefore, antiviral drugs or additives are used to rapidly stop the spread of the virus during FMD outbreaks. Manganese (Mn²⁺) was recently found to be an important substance necessary for the host to protect against DNA viruses. However, its antiviral effect against RNA viruses remains unknown. In this study, we found that Mn²⁺ has antiviral effects on the FMD virus (FMDV) both in PK15 cells and mice. The inhibitory effect of Mn²⁺ on FMDV involves NF-κB activation and up-regulation of interferon-stimulated genes. Animal experiments showed that Mn²⁺ can be highly effective in protecting C57BL/6N mice from being infected with FMDV. Overall, we suggest Mn²⁺ as an effective antiviral additive for controlling FMDV infection.

Both Manganese (Mn²⁺) and MSA-2 can activate the downstream signal pathway through stimulator of interferon genes (STING) and induce the expression of type I interferon, which is important for hosts to protect against DNA viruses. However, its effect on RNA viruses remains unknown. In this study, we used Seneca Valley virus (SVV) as a model RNA virus to investigate the inhibitory effects of Mn²⁺ and MSA-2 on the virus replication in the porcine cells (PK-15 cells). The results showed that both MSA-2 and Mn²⁺ were able to inhibit the SVV replication in PK-15 cells. The combination of MAS-2 and Mn²⁺ could confer better protection against SVV. Further studies showed that MSA-2 and Mn²⁺ could activate TBK1, IRF3 and NFκB through STING and induce the expression of IFN-β, IL-6 and TNF-α. The present study confirmed that MSA-2 synergized with Mn²⁺ in STING activation to generate a better antiviral effect in vitro, which would be helpful for the further development of effective antiviral drugs in the future.

Canine distemper (CD) is a highly infectious disease of dogs which is caused by canine distemper virus (CDV). Previous studies have demonstrated that CDV infection can induce autophagy in cells. However, the mechanism underlying CDV-induced autophagy remains not fully understood. The CDV non-structural protein V plays a vital role in viral replication and pathogenicity in the host. In this study, we investigated the relationship between the CDV-V protein and autophagy induction and further explored its impact on the viral replication and the mechanism behind this. Our results showed that the V protein induced autophagy via inhibiting the phosphorylation of PI3K, AKT, and mTOR to promote viral replication. The activation or inhibition of PI3K phosphorylation resulted in enhancing or reducing viral replication, respectively. Further studies revealed that the V protein interacted with PI3K to induce cellular autophagy. The present study demonstrated that the CDV-V protein can induce cellular autophagy by inhibiting the PI3K/AKT signaling pathway to enhance viral replication. The results improve the understanding of the molecular mechanism of CDV infection and offer new perspectives for the development of effective treatment and prevention strategies.

Cellular autophagy is a self-protection mechanism that exists universally in eukaryotes to renew intracellular substances and maintain the homeostasis of the internal environment. Recent studies have shown that cellular autophagy can be involved in the infection process of Picornavirus. When small RNA viruses infect cells, autophagy pathway is activated rapidly and autophagy can play the function of antiviral natural immunity by delivering viral antigens. At the same time, autophagy provides replication-associated proteins and non-cellular cleavage release pathway for part of Picornavirus to promote the replication of the viruses. In this paper, we review the progress of the interaction between Picornavirus and cellular autophagy in recent years, and provide reference for further elucidation of the mechanism of Picornavirus involved in the regulation of autophagy.

Viral infection triggers an immune response through signal transduction. Cyclic guanosine-adenylate synthetase (cGAS) recognises viral DNA and interacts with the interferon gene stimulating protein (STING) to mediate the production of interferon type 1 (IFN1). The retinoic acid-inducible gene 1 (RIG-1) receptor recognises viral RNA and activates IFN1 by triggering the RIG-1 signalling pathway via the mitochondrial antiviral signalling protein (MAVS). STING not only serves as a DNA viral signalling pathway protein, but also interacts with MAVS and participates in the RNA viral signalling pathway. However, the proteases of RNA viruses, such as dengue virus and hepatitis C virus, escape from the immune system by interacting with STING and inhibit IFN production. In this paper, we review the interaction mechanism between STING and MAVS, and the escape of RNA viruses from the immune system through STING, in order to provide new ideas for the study of viral escape from the natural immune regulation mechanism. Cellular autophagy is a metabolic process widely found in eukaryotic organisms, which is mainly involved in maintaining cellular homeostasis and cellular material recycling by degrading damaged organelles and macromolecules in cells. It has been found that autophagy can participate in the infection process of RNA viruses, and the viruses have evolved a certain mechanism to regulate autophagy to promote their own proliferation. In this paper, we also review the progress of the interaction between RNA virus infection and cellular autophagy in recent years, with a view to providing some reference for antiviral research.