Porcine deltacoronavirus (PDCoV) infection suppresses RIG-I-mediated interferon-β production

Abstract

Porcine deltacoronavirus (PDCoV), an emerging animal coronavirus causing enteric disease in pigs, belongs to the newly identified Deltacoronavirus genus in the Coronaviridae family. Although extensive studies have been carried out to investigate the regulation of interferon (IFN) responses by alphacoronaviruses, betacoronaviruses, and gammacoronaviruses, little is known about this process during deltacoronavirus infection. In this study, we found that PDCoV infection fails to induce, and even remarkably inhibits, Sendai virus- or poly(I: C)-induced IFN-β production by impeding the activation of transcription factors NF-κB and IRF3. We also found that PDCoV infection significantly suppresses the activation of IFN-β promoter stimulated by IRF3 or its upstream molecules (RIG-I, MDA5, IPS-1, TBK1, IKKε) in the RIG-I signaling pathway, but does not counteract its activation by the constitutively active mutant of IRF3 (IRF3-5D). Taken together, our results demonstrate that PDCoV infection suppresses RIG-I-mediated IFN signaling pathway, providing a better understanding of the PDCoV immune evasion strategy.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I

“…In order to yield relevant biological information consistent with in vivo SADS-CoV infection, we employed IPEC-J2 cells as a model to investigate molecular mechanisms underlying SADS-CoV infection. Our results showed that similar to PEDV, PDCoV and PPRSV (Luo et al, 2008;Cao et al, 2015;Luo et al, 2016), SADS-CoV did not induce IFN-β production and inhibited poly(I:C) or SeV-mediated IFN-β expression, which suggested that this may play a crucial role for the pathogenesis of these viruses.…”

“…Previous studies indicate that the coronavirus mainly interacts on the RIG-I signaling pathway to interrupt IFN expression (Likai et al, 2019;Zhu et al, 2017b;Luo et al, 2016). As mentioned above, IRF3 activity showed a little decrease in SADS-CoV infected cells, there is a possibility that SASD-CoV infection may act on IRF3 to inhibit INF-β expression.…”

“…Porcine epidemic diarrhea virus (PEDV) interacted with IPS-1 to inhibit IFN-β transcription in porcine small intestinal epithelial cells (Cao et al, 2015). Porcine deltacoronavirus (PDCoV) suppressed IFN-β production by blocking the activation of transcription factors IRF3 and NF-κB in a porcine kidney cell line, LLC-PK1 cells (Luo et al, 2016). Although Transmissible gastroenteritis virus (TGEV) infection didn't suppress IFN-β induction, it induced a delayed activation of the IFN response in IPEC-J2 cells (Zhu et al, 2017a).…”

Porcine deltacoronavirus induces TLR3, IL-12, IFN-α, IFN-β and PKR mRNA expression in infected Peyer’s patches in vivo

“…PDCoV is an important enteropathogen in pigs, but few reports are involved in modulation of the host immune responses against PDCoV infection. Currently it is known that PDCoV infection inhibits the production of interferon-beta (IFN-β) through suppressing the activation of RIG-signaling pathway (Luo et al, 2016) in vitro. Nonstructural protein 5 (nsp5) of PDCoV was a newly identified IFN antagonist by cleaving NEMO (Zhu et al, 2017a) and destroyed subsequent type I interferon signaling by cleaving STAT2 (Zhu et al, 2017b).…”

Virulence factors in porcine coronaviruses and vaccine design

“…In fact, it has been shown that virulent PEDV induces an increased NF-κB activation and pro-inflammatory cytokine production compared with an attenuated vaccine-like strain (Guo et al, 2016). Similarly to PEDV, PDCoV infection has been recently reported to inhibit IFN production in cell culture (Luo et al, 2016). …”