Conserved Antagonization of Type I Interferon Signaling by GP5 Proteins.

can establish persistent infections in animals such as equids, pigs, nonhuman primates, rodents, and possums. Some 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. 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 glycoprotein 5 (GP5) protein in IFN signaling inhibition remains unclear. Here, we investigated the inhibitory activity of 47 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, GP5 proteins showed a conserved inhibitory activity against IFN-β signaling, induced by either pig or human TRIF. Furthermore, certain GP5 proteins could inhibit the induction of IFN-stimulated genes. These findings highlight the role of GP5 proteins in supporting persistent infection.