Death Receptor DR5 as a Proviral Factor for Viral Entry and Replication of Coronavirus PEDV

Viruses. 2022 Dec 6;14(12):2724. doi: 10.3390/v14122724.

Abstract

Porcine epidemic diarrhea virus (PEDV), a member of Coronaviridae, causes high mortality in newborn piglets, and has caused significant economic losses in the pig industry. PEDV infection can induce apoptosis, both caspase-dependent and caspase-independent, but the details of apoptosis remain clarified. This study investigated the effect of death receptor DR5 on PEDV infection and its relationship with PEDV-induced apoptosis. We found that DR5 knockdown reduced viral mRNA and protein levels of PEDV, and the viral titer decreased from 104.5 TCID50 to 103.4 TCID50 at 12 hpi. Overexpression of DR5 significantly increased the viral titer. Further studies showed that DR5 facilitates viral replication by regulating caspase-8-dependent apoptosis, and the knockdown of DR5 significantly reduced PEDV-induced apoptosis. Interestingly, we detected a biphasic upregulation expression of DR5 in both Vero cells and piglets in response to PEDV infection. We found that DR5 also facilitates viral entry of PEDV, especially, incubation with DR5 antibody can reduce the PEDV binding to Vero cells. Our study improves the understanding of the mechanism by which PEDV induces apoptosis and provides new insights into the biological function of DR5 in PEDV infection.

Keywords: PEDV; apoptosis; death receptor 5; viral entry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspases
  • Chlorocebus aethiops
  • Coronavirus Infections*
  • Coronavirus*
  • Porcine epidemic diarrhea virus* / genetics
  • Proviruses
  • Receptors, Death Domain
  • Swine
  • Swine Diseases*
  • Vero Cells
  • Virus Internalization

Substances

  • Caspases
  • Receptors, Death Domain

Grants and funding

This work was supported by the National Natural Science Foundation of China (32172821) and a CAU Grant for the Prevention and Control of Immunosuppressive Disease in Animals of the China Agricultural University.