Angiotensin Converting Enzyme 2 Does Not Facilitate Porcine Epidemic Diarrhea Virus Entry into Porcine Intestinal Epithelial Cells and Inhibits It-induced Inflammatory Injury by Promoting STAT1 Phosphorylation

Virus Res. 2023 Dec 11:199300. doi: 10.1016/j.virusres.2023.199300. Online ahead of print.ABSTRACTACE2 has been confirmed to be a functional receptor for SARS-CoV and SARS-CoV-2, but research on animal coronaviruses, especially PEDV, are still unknown. The present study investigated whether ACE2 plays a role in receptor recognition and subsequent infection during PEDV invasion of host cells. IPEC-J2 cells stably expressing porcine ACE2 did not increase the production of PEDV-N but inhibited its expression. Porcine ACE2 knockout cells was generated by CRISPR/Cas9 genome editing in IPEC-J2 cells. The expression of PEDV-N did not decrease but slightly increased. The Co-IP results showed that there was no significant association between ACE2 and PEDV-S. There were no obvious interaction between PEDV-S, PEDV-E, PEDV-M and porcine ACE2 promoters, but PEDV-N could inhibit the activity of ACE2 promoters. PEDV-N degraded STAT1 and prevented its phosphorylation, thereby inhibiting the expression of interferon-stimulated genes. Repeated infection of PEDV further confirmed the above results. PEDV activated ACE-Ang II-AT1R axis, while ACE2-Ang (1-7)-MasR axis activity was decreased and inflammatory response was intensified. However, excess ACE2 can reverse this reaction. These results reveal that ACE2 does not facilitate PEDV entry into cells, but relieves PEDV-induced inflammation by promoting STAT1 phosphorylation.PMID:38092254 | DOI:10.1016/j.virusres.2023.199300
Source: Virus Research - Category: Virology Authors: Source Type: research