# Conserved Antagonization of Type I Interferon Signaling by Arterivirus GP5 Proteins

## TL;DR

This study shows that Arterivirus GP5 proteins block interferon signaling in host cells, helping the virus avoid detection and cause persistent infections.

## Contribution

The study reveals that Arterivirus GP5 proteins universally inhibit TRIF-mediated interferon signaling across multiple species.

## Key findings

- All 47 Arterivirus GP5 proteins inhibit TRIF-mediated IFN-β signaling by promoting TRIF degradation.
- GP5 proteins block IFN-β signaling in both pig and human TRIF systems.
- Some GP5 proteins also inhibit the induction of IFN-stimulated genes.

## Abstract

Arteriviruses can establish persistent infections in animals such as equids, pigs, nonhuman primates, rodents, and possums. Some Arteriviruses can even cause overt and severe diseases such as Equine Arteritis in horses and Porcine Reproductive and Respiratory Syndrome in pigs, leading to huge economic losses. Arteriviruses have evolved viral proteins to antagonize the host cell’s innate immune responses by inhibiting type I interferon (IFN) signaling, assisting viral evasion and persistent infection. So far, the role of the Arterivirus glycoprotein 5 (GP5) protein in IFN signaling inhibition remains unclear. Here, we investigated the inhibitory activity of 47 Arterivirus GP5 proteins derived from various hosts. We demonstrated that all GP5 proteins showed conserved activity for antagonizing TIR-domain-containing adapter proteins inducing interferon-β (TRIF)-mediated IFN-β signaling through TRIF degradation. In addition, Arterivirus GP5 proteins showed a conserved inhibitory activity against IFN-β signaling, induced by either pig or human TRIF. Furthermore, certain Arterivirus GP5 proteins could inhibit the induction of IFN-stimulated genes. These findings highlight the role of Arterivirus GP5 proteins in supporting persistent infection.