The Insufficient Activation of RIG-I-Like Signaling Pathway Contributes to Highly Efficient Replication of Porcine Picornaviruses in IBRS-2 Cells

Seneca Valley virus (SVV) or commonly known as senecavirus A, is one of the picornavirus that is associated with vesicular disease and neonatal mortality in swine herds. Our previous study found that SW replicates extremely faster in porcine Instituto Biologico-Rim Suino-2 (IBRS-2) cells than that in porcine kidney-15 (PK-15) cells. However, the underlying mechanism remains unknown. In this study, we comprehensively compared the expression features between IBRS-2 cells and PK-15 cells in response to SW infection by an unbiased high-throughput quantitative proteomic analysis. We found that the innate immune response-related pathways were efficiently activated in PK-15 cells but not in IBRS-2 cells during SW infection. A large amount of interferon (IFN)-stimulated genes were induced in PK15 cells. In contrast, no IFN-stimulated genes were induced in I BRS-2 cells. Besides, we determined similar results in the two cell lines infected by another porcine picornavirus footand-mouth disease virus. Further study demonstrated that the Janus kinase signal transducer and activator of transcription signaling pathway was functioning properly in both IBRS-2 and PK-15 cells. A systematic screening study revealed that the aberrant signal transduction from TANK-binding kinase 1 to IFN regulatory factor 3 in the retinoic acid-inducible gene I-like receptor signaling pathway in IBRS-2 cells was the fundamental cause of the different innate immune response manifestation and different viral replication rate in the two cell lines. Together, our findings determined the different features of IBRS-2 and PK-15 cell lines, which will help for clarification of the pathogenesis of SW. Besides, identification of the underlying mechanisms will provide new targets and an insight for decreasing the viral clearance rate and probably improve the oncolytic effect by SW in cancer cells.

Automated summary

By comparing the expression features of IBRS-2 and PK-15 cells in response to SVV infection, differences in innate immune response were identified, with aberrant signal transduction found to be the underlying cause of distinct immune response and viral replication rates between the two cell lines.