Differential gene modulation of pattern-recognition receptor TLR and RIG-I-like and downstream mediators on intestinal mucosa of pigs infected with PEDV non S-INDEL and PEDV S-INDEL strains

• Published in: Virology (New York, N.Y.) Vol. 517; pp. 188 - 198
• Main Authors: Temeeyasen, G., Sinha, A., Gimenez-Lirola, L.G., Zhang, J.Q., Piñeyro, P.E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2018
• Subjects: Animals; Canonical pathway; Coronavirus Infections - veterinary; Coronavirus Infections - virology; Cytokines - genetics; Cytokines - metabolism; Gene Expression Regulation - immunology; INDEL Mutation; Intestinal Mucosa - metabolism; Intestinal Mucosa - virology; IRF7; MyD88; NF-κB; Porcine epidemic diarrhea virus; Porcine epidemic diarrhea virus - genetics; Porcine epidemic diarrhea virus - physiology; Pro-inflamatory cytokines; RIG-I-like receptors; Swine; Swine Diseases - virology; Toll-like receptor; Toll-Like Receptors - genetics; Toll-Like Receptors - metabolism; TRAF6; Type 1 interferon; NF-κB; Porcine epidemic diarrhea virus; Type 1 interferon; TRAF6; IRF7; RIG-I-like receptors; MyD88; Canonical pathway; Toll-like receptor; Pro-inflamatory cytokines
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2017.11.024

Porcine epidemic diarrhea virus (PEDV) strains can be divided into non-S-INDEL and S-INDEL strains. PEDV pathogenesis is strain-specific, and studies in neonatal pigs have demonstrated that the PEDV non-S-INDEL strains are more pathogenic than the PEDV S-INDEL strains. RNA viruses, including PEDV, can interact with a large number of pattern recognition receptors (PRRs) in the intestinal mucosa, including toll-like receptors (TLRs) and RIG-I-like receptors (RLRs). We investigated the differential gene modulation of TLRs, RIG-I, and downstream mediators on the intestinal mucosa of neonatal pigs infected with PEDV S-INDEL and non-S-INDEL strains. Ten five-day-old piglets were inoculated orally with 10ml of 104 TCDI50/ml of either PEDV non-S-INDEL or S-INDEL strains. PEDV S-INDEL infection induced pro-inflammatory cytokines through the non-canonical NF-κB signaling pathway by activating RIG-I. In contrast, PEDV non-S-INDEL infection suppressed the induction of pro-inflammatory cytokines and type 1 interferon production by down-regulation of TLRs and downstream signaling molecules. •Differential gene modulation of TLR and RIG-I-like receptors and downstream mediators.•PEDV S-INDEL induces pro-inflammatory cytokines through non-canonical NF-κB signaling pathway.•PEDV S-INDEL pro-inflammatory cytokines activation is RIG-I dependent.•PEDV non-S-INDEL suppresses the induction of pro-inflammatory cytokines and type 1 interferon.•PEDV non-S-INDEL effect is mediated by down-regulation of TLRs and its downstream-signaling molecules.•PEDV S-INDEL and PEDV non-S-INDEL cause differential modulation on innate immune response pathways.•Differential modulation could be translated into differences in pathogenesis and clinical outcomes.