Low-level contamination of deoxynivalenol: A threat from environmental toxins to porcine epidemic diarrhea virus infection

Mycotoxins are toxic metabolites produced by Fungal species that commonly present in the global environment, especially in cereals and animal forages. The changing global environment may further increase the exposure to these toxins, posing a serious threat to humans and Animals. Recently, coronavirus has become one of the most important pathogens threatening human and animal health. It is not clear whether environmental toxins, such as mycotoxins, will affect coronavirus Infection. Given that pigs are among the Animals most affected by coronavirus and highly homologous to humans, weaned piglets and IPEC-J2 cells were respectively chosen as in vivo and in vitro model to explore the impacts of deoxynivalenol (DON), the most abundant trichothecene mycotoxin in feed, on porcine epidemic diarrhea virus (PEDV) Infection and the mechanisms involved. In vivo, twenty-seven piglets infected naturally with PEDV were randomly divided into three groups, receiving the basal diet containing 0, 750 and 1500 μg/kg DON, respectively. Significant increases in the diarrhea rates, gut barrier injury and PEDV proliferation of piglets' small intestine were observed in experimental groups compared with the control. Additionally, the autophagosome-like vesicles and the autophagy-related proteins expression were also increased in experimental groups. In vitro, we observed that 0.1, 0.5 and 1.0 μM DON significantly promoted the entry and replication of PEDV in IPEC-J2 cells, along with the induction of a complete Autophagy. CRISPR-Cas9-mediated knockout of LC3B indicated a vital role of Autophagy in the promotion. Pretreatment with p38 signaling inhibitor could significantly block the induction of Autophagy, indicating that DON could promote the PEDV Infection by triggering p38-mediated Autophagy. Our findings suggest that mycotoxin could influence the prevalence of coronavirus and provide new ideas for the prevention and control of coronavirus.