Abstract:

Angiotensin-converting enzyme 2 (ACE2) plays a role in the regulation of various tissues and organs in the body, and its role in maintaining intestinal homeosta has become widely accepted. However, its role in animal coronaviruses, especially in porcine epidemic diarrhea virus (PEDV) infection, is still unclear. By analyzing the relationship between ACE2 and the pathological changes in intestinal tissues of clinically infected piglets with PEDV, the correlation between ACE2 and PEDV infection was studied. With PED clinically infected piglets as research objects, duodenum, jejunum and ileum tissues were isolated and intercepted. PCR, histopathology, Western blot, RT-qPCR and Spearman correlation analysis were used to determine PEDV infection and its expression distribution in the small intestine, observe the pathological changes in the small intestine, and analyze the expression changes of ACE2, IFN-α and related factors in the small intestine. To investigate the role of ACE2 and PEDV infection. The results showed that PEDV infection was found in the small intestine of piglets and distributed in the jejunum and ileum. PEDV infection caused necrosis and shedding of small intestinal epithelial cells, atrophy and shortening of intestinal villi, etc. The contents of Ang Ⅱ and pro-inflammatory factors TNF-α, IL-6, IL-8 and IL-1β in the small intestine were significantly increased, while the contents of Ang (1-7) and anti-inflammatory factors TGF-β1 and IL-10 were significantly decreased. The expression of ACE2, MasR, and IFN-α protein, as well as the expression of ISG15, ISG54, and ISG56 mRNA mediated by IFN-α, were all significantly downregulated, while the expression of ACE and AT1R proteins was all significantly upregulated. PEDV infection was negatively correlated with the ACE2-Ang (1-7)-MasR axis and positively correlated with the ACE-Ang Ⅱ-AT1R axis, negatively correlated with IFN-α expression, while ACE2 was positively correlated with IFN-α expression. The results suggest that PEDV infection induces intestinal inflammatory lesions in piglets, with both the expression of IFN-α and the ISGs mediated by it being suppressed in the small intestine. All members of the renin-angiotensin system (RAS) are present locally in the intestine, and two of its pathways are involved in the inflammatory injury process of PEDV-induced intestinal lesions in piglets, characterized by the activation of the ACE-Ang Ⅱ-AT1R axis and the inhibition of the ACE2-Ang (1-7)-MasR axis. ACE2 is closely related to PEDV infection and its induced interferon response.

Key words: angiotensin converting enzyme 2, porcine epidemic diarrhea virus, small intestine, interferon, intestinal inflammation