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

## TL;DR

This study shows that the SHP-1 protein helps the PEDV virus replicate in pigs by weakening the immune response.

## Contribution

The novel finding is that porcine SHP-1 promotes PEDV replication by inhibiting TRAF3-mediated interferon responses.

## Key findings

- SHP-1 overexpression increases PEDV S protein mRNA levels in PK15 cells.
- SHP-1 inhibits TRAF3 ubiquitination, reducing IFN-β and ISG expression.
- SHP-1 knockdown decreases viral replication and increases interferon-related gene expression.

## Abstract

Porcine epidemic diarrhea virus (PEDV), a member of the genus Alpha 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 IFN-β, TNF-α, ISG15, and CXCL10, 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 IFN-β and ISGs and facilitating PEDV replication. The study provided new insights for the prevention and control of porcine epidemic diarrhea.