Abstract:[Background] Senecavirus A (SVA) is a novel pathogen that causes an infectious viral disease in pigs. SVA, a member of the genus Senecavirus of the family Picornaviridae, has a single-stranded positive-sense RNA genome. SVA can infect pigs of all ages, causing neonatal mortality and blisters on the feet and in or around the mouth of pigs. Innate immunity is the first line of host defense against viral invasion, while the role of the mechanism of the interaction between SVA and host innate immune responses remains unknown.[Objective] To investigate the role of the 2C protein of SVA in innate immune responses. [Methods] RT-qPCR and Western blotting were employed to analyze the effect of 2C protein on cytokine expression and signaling pathway in host PK-15 cells overexpressing 2C protein or were infected with SVA. [Results] The infection of SVA significantly up-regulated the expression of interferon beta (IFNβ), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in host PK-15 cells. Meanwhile, SVA infection resulted in the phosphorylation of TANK-binding kinase 1 (TBK1) and Nuclear factor-kappa B (NF-κB). Further studies revealed that 2C protein activated TBK1 and NF-κB and induced the expression of IFNβ, TNF-α, and IL-6. In addition, 2C protein activated the stimulator of interferon genes (STING), a key protein against DNA virus infection. The knockout of STING suppressed the phosphorylation of TBK1 and NF-κB as well as the expression of IFNβ, TNF-α, and IL-6. [Conclusion] This study preliminary reveals that the 2C protein of SVA activates STING to induce the innate immune responses. The findings uncover the regulatory role of STING in the RNA virus SVA-mediated immune response, which provide a theoretical basis for the research and development of antiviral drugs and vaccines.
