期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.00363
关键词
Senecavirus A; Seneca Valley virus; apoptosis; 3C protease; virus egress
类别
资金
- USDA National Institute of Food and Agriculture [SD00H517-14, SD00R518-14]
- South Dakota Governor's Office for Economic Development grant
- MorriSTONE graduate scholarship
Senecavirus A (SVA), an oncolytic picornavirus used for cancer treatment in humans, has recently emerged as a vesicular disease (VD)-causing agent in swine worldwide. Notably, SVA-induced VD is indistinguishable from foot-and-mouth disease (FMD) and other high-consequence VDs of pigs. Here we investigated the role of apoptosis on infection and replication of SVA. Given the critical role of the nuclear factor-kappa B (NF-kappa B) signaling pathway on modulation of cell death, we first assessed activation of NF-kappa B during SVA infection. Results here show that while early during infection SVA induces activation of NF-kappa B, as evidenced by nuclear translocation of NF-kappa B-p65 and NF-KB-mediated transcription, late in infection a cleaved product corresponding to the C-terminus of NF-kappa B-p65 is detected in infected cells, resulting in lower NF-kappa B transcriptional activity. Additionally, we assessed the potential role of SVA 3C protease (3C(pro)) in SVA-induced host-cell apoptosis and cleavage of NF-kappa B-p65. Transient expression of SVA 3C(pro) was associated with cleavage of NF-kappa B-p65 and Poly (ADP-ribose) polymerase (PARP), suggesting its involvement in virus-induced apoptosis. Most importantly, we showed that while cleavage of NF-kappa B-p65 is secondary to caspase activation, the proteolytic activity of SVA 3C(pro) is essential for induction of apoptosis. Experiments using the pan-caspase inhibitor Z-VAD-FMK confirmed the relevance of late apoptosis for SVA infection, indicating that SVA induces apoptosis, presumably, as a mechanism to facilitate virus release and/or spread from infected cells. Together, these results suggest an important role of apoptosis for SVA infection biology.
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