Modulation of Innate Antiviral Immune Response by Porcine Enteric Coronavirus

Abstract

Host's innate immunity is the front-line defense against viral infections, but some viruses have evolved multiple strategies for evasion of antiviral innate immunity. The porcine enteric coronaviruses (PECs) consist of porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), transmissible gastroenteritis coronavirus (TGEV), and swine acute diarrhea syndrome-coronavirus (SADS-CoV), which cause lethal diarrhea in neonatal pigs and threaten the swine industry worldwide. PECs interact with host cells to inhibit and evade innate antiviral immune responses like other coronaviruses. Moreover, the immune escape of porcine enteric coronaviruses is the key pathogenic mechanism causing infection. Here, we review the most recent advances in the interactions between viral and host's factors, focusing on the mechanisms by which viral components antagonize interferon (IFN)-mediated innate antiviral immune responses, trying to shed light on new targets and strategies effective for controlling and eliminating porcine enteric coronaviruses.

Keywords: PDCoV; PEDV; SADS-CoV; TGEV; immune evasion; innate immunity response; porcine enteric coronaviruses.

Figure 1

Schematic diagram of porcine enteric coronaviruses (PECs). (A) Genome structure of PDEV; (B) Genome structure of transmissible gastroenteritis coronavirus (TGEV); (C) Genome structure of swine acute diarrhea syndrome-coronavirus (SADS-CoV); (D) Genome structure of porcine deltacoronavirus (PDCoV). S, spike; E, envelope; M, membrane; N, nucleoprotein; and Ns, accessory genes.

Figure 2

Potential mechanisms of porcine enteric coronavirus (PEC) structural proteins antagonize innate antiviral immune response. Different structural proteins of different porcine enteric coronaviruses used different strategies to antagonize the host’s immune responses. During PEC infection, interferons (IFNs) and pro-inflammatory are activated to fight against invading virus. It is noteworthy that STAT, retinoic acid-inducible gene I (RIG-I), and nuclear factor-κB (NF-κB) signalings are involved in this structural proteins-induced immune evasion. stands for negative regulation, stands for positive regulation.

Figure 3

Non-structural protein (NSP) of porcine enteric coronavirus (PEC) antagonizes innate immune response. Retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and Toll-like receptors (TLRs) recognize the invading virus and induce pro-inflammatory cytokines, type I/III interferons (IFNs) by nuclear factor-κB (NF-κB) and (RIG-I)-like receptors (RLRs) signaling pathway, respectively. Extracellular Type I and III IFNs recognized by IFN-I receptor (IFNAR) and type III IFN receptor (IFNLR) to phosphorylate JAK1 and TYK2. And then, STAT1/2 is recruited and phosphorylated to form three STAT complexes. STAT1 and STAT2 form heterodimers and recruit IRF9 or IRF1. These complexes enter the nucleus and induce type I and III ISGs, inflammatory cytokines production. NSPs of PEC antagonize various steps of this antiviral response. stands for negative regulation; stands for type I IFN; and stands for type III IFN.