# Pseudorabies Virus IE180 Inhibits Virus Replication by Activating the Type I Interferon Pathway

## TL;DR

This study shows that the PRV protein IE180 inhibits virus replication by activating the host's type I interferon immune response.

## Contribution

IE180 is identified as a novel viral protein that activates the IFN-I pathway to restrict viral replication.

## Key findings

- IE180 overexpression inhibits PRV and H1N1 replication in cells with functional IFN-I signaling.
- IE180 activates the IFN-β promoter and increases ISG expression.
- The ICP4-Like2 domain of IE180 is essential for its antiviral activity.

## Abstract

The immediate-early protein IE180 of pseudorabies virus (PRV) is a multifunctional regulator of viral and host gene expression. However, its role in modulating antiviral immune responses remains poorly understood. Here, we demonstrate that IE180 overexpression significantly inhibits PRV and H1N1 influenza virus replication in Hep2 and A549 cells, respectively. Mechanistically, IE180 activates the type I interferon (IFN-I) pathway by enhancing IFN-β promoter activity and IFN transcription, leading to upregulated expression of interferon-stimulated genes (ISGs). Notably, IE180 failed to suppress PRV or H1N1 replication in Vero cells, which lack functional IFN-I signaling, confirming the dependence of its antiviral function on the IFN-I pathway. Domain mapping revealed that the ICP4-Like2 domain of IE180 is critical for IFN-β activation and antiviral activity. These findings establish IE180 as a novel viral immunomodulator that activates host innate immunity to restrict viral replication, providing insights into PRV-host interactions and potential therapeutic strategies.