SHP-1 Promotes the Replication of Porcine Epidemic Diarrhea Virus by Inhibiting TRAF3-Mediated Type I Interferon Immune Responses

Porcine epidemic diarrhea virus (PEDV), a member of the genus <i>Alpha</i> coronavirus, is one of the main pathogens causing piglet diarrhea. PEDV can enhance its replication by regulating host protein function. The tyrosine phosphatase src homology 2 domain-containing PTP (SHP-1) acts as a host natural immune protein capable of influencing viral replication, but there are no studies on the regulation of virus replication by pig SHP-1. In this study, we expressed porcine SHP-1 protein and examined its interaction with PEDV as well as its potential role in PEDV infection. The results showed that SHP-1 overexpression in porcine kidney cells (PK15) significantly increased the mRNA level of viral S protein in a dose-dependent manner. In contrast, SHP-1 knockdown reduced S gene expression, indicating that SHP-1 promoted PEDV replication. Overexpression of SHP-1 had an inhibitory effect on <i>IFN-β</i>, <i>TNF-α</i>, <i>ISG15</i>, and <i>CXCL10</i>, while this inhibition was reduced as SHP-1 expression decreased. Furthermore, we found that SHP-1 interacted with TNF receptor-associated factor 3 (TRAF3) and inhibited its K63-linked ubiquitination, suppressing the expression of <i>IFN-β</i> and <i>ISG</i>s and facilitating PEDV replication. The study provided new insights for the prevention and control of porcine epidemic diarrhea.