# Mpox virus OPG175 negatively regulates viral replication by controlling Wnt signaling

## TL;DR

This study shows that the Mpox virus clade IIb has lower replication due to high OPG175 expression, which activates Wnt signaling to inhibit viral spread.

## Contribution

The study identifies OPG175 as a novel viral gene that regulates replication through Wnt signaling in MPXV clade IIb.

## Key findings

- OPG175 overexpression reduces MPXV replication efficiency.
- OPG175 knockdown increases MPXV infectious titer.
- Wnt signaling activation inhibits MPXV replication.

## Abstract

Mpox virus (MPXV) infection exhibits different case fatality rates and symptoms depending on its clade. However, there has been insufficient molecular biological analysis of the differences between clades. Here, we investigated whether clades can be distinguished by focusing on the expression of MPXV genes. The replication efficiency of MPXV clade IIb, responsible for the 2022 mpox outbreak, was lower than that of clades Ia and IIa. We found that OPG175 was highly expressed in MPXV clade IIb-infected cells. Suppression of OPG175 expression significantly increased the infectious titer of MPXV, whereas OPG175 overexpression significantly decreased it. We also found that OPG175 overexpression enhanced the expression of Wnt signaling-related genes, and activation of Wnt signaling decreased MPXV replication efficiency. Therefore, high OPG175 expression in MPXV clade IIb-infected cells likely inhibits MPXV replication via activation of Wnt signaling.

•OPG175 is highly expressed in MPXV clade IIb-infected cells•OPG175 overexpression decreased MPXV infection efficiency•OPG175 knockdown increased MPXV infection efficiency•OPG175 overexpression activated Wnt signaling

OPG175 is highly expressed in MPXV clade IIb-infected cells

OPG175 overexpression decreased MPXV infection efficiency

OPG175 knockdown increased MPXV infection efficiency

OPG175 overexpression activated Wnt signaling

Immunology; Virology; Transcriptomics