Seneca Valley Virus (SVV) is a newly emerged virus belonging to the family Picornaviridae. Basic knowledge of the immunological response to SVV is limited. To date, one study has demonstrated that SVV 3C mediates the cleavage of host MAVS, TRIF, and TANK at specific sites and consequently escapes the host's antiviral innate immunity. In this study, we show that SVV 3C reduces IRF3 and IRF7 protein expression level and phosphorylation. SVV infection also reduces expression of IRF3 and IRF7 protein. The degradation of IRF3 and IRF7 is dependent on the 3C protease activity. We also identify interactions between 3C and IRF3 and IRF7 in PK-15 cells. A detailed analysis revealed that the degradation of IRF3 and IRF7 blocks the transcription of IFN-β, IFN-α1, IFN-α4, and ISG54. Together, our results demonstrate a novel mechanism developed by SVV 3C to allow the virus to escape the host's intrinsic innate immune system.

Foot-and-mouth disease (FMD) is a highly contagious virus that affects cloven-hoofed animals. To understand better the role of nonstructural protein 2B of the causative agent FMD virus (FMDV) in the process of virus replication, we identified a porcine host protein, cyclophilin A (CypA), which interacts with FMDV 2B. The 2B-CypA interaction was confirmed by coimmunoprecipitation and GST pull-down assays. CypA showed antiviral functions during FMDV infection. Overexpression of CypA decreased FMDV leader protein (L) and 3A at protein levels. CypA-induced reduction of L enhanced the synthesis of host proteins and increased the integrality of host eukaryotic translation initiation factor (eIF)-4γ (eIF4G). The reduction of L and 3A was dependent on the proteasome pathway. No interaction was identified between CypA and L or 3A. However, CypA-induced reduction of L and 3A was suppressed by 2B, and disruption of 2B-CypA interaction impaired this inhibitive effect induced by 2B. In summary, our findings identify the antiviral role of CypA against FMDV and provide key insights into how FMDV antagonizes host antiviral response by 2B protein.-Liu, H., Xue, Q., Cao, W., Yang, F., Ma, L., Liu, W., Zhang, K., Liu, X., Zhu, Z., Zheng, H. Foot-and-mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication.

Lysophosphatidic acid (LPA), a simple water-soluble glycerophospholipid with growth factor-like activity, regulates certain behaviors of multiple cancer types by binding to its receptor, LPA receptor 2 (LPA2). Notch1 is a key mediator in multiple human cancer cell types. The association between LPA2 and Notch1 in gastric cancer cells is not well known. The present study aimed to investigate the function of LPA2 and Notch1 in controlling the migration and invasion activities of SGC-7901 gastric cancer cells following stimulation with LPA. It was revealed that LPA may stimulate the expression of Notch1 and Hes family bHLH transcription factor 1, and the phosphorylation of protein kinase B which belongs to the Notch pathway. Furthermore, by performing transwell migration and invasion assays, immunofluorescent staining, analyzing the expression of markers for the epithelial-mesenchymal transition (EMT) and downregulating LPA2 and Notch1 expression, it was verified that LPA2 and Notch1 mediated the metastasis, invasion, EMT and rebuilding of the cytoskeleton of SGC-7901 cells upon LPA treatment. An immunoprecipitation assay revealed that LPA2 interacted with Notch1 in SGC-7901 cells. The present study may provide novel ideas and an experimental basis for identifying the factors that affect the functions of SGC-7901 cells.