Mpox virus OPG175 negatively regulates viral replication by controlling Wnt signaling

Sep 28, 2026

Study of mpox virus (MPXV) clades addresses differences in case fatality and symptoms, but clade-level molecular mechanisms remain insufficient. This work compares MPXV clade IIb replication efficiency with clades Ia and IIa by examining viral gene expression. OPG175 is highly expressed in IIb-infected cells, and manipulating OPG175 alters infectious titers. OPG175 overexpression activates Wnt signaling–related gene expression, and Wnt activation suppresses MPXV replication efficiency.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Summary

Introduction

Mpox clades and outbreak context

MPXV genome structure and protein functions

iScience Article Mpox virus OPG175 negatively regulates viral replication by controlling Wnt signaling Authors Yoshitaka Nakata, Masako Yamasaki, Yukio Watanabe, , Kei Sato, Akatsuki Saito, Kazuo Takayama Correspondence [keisato@g.ecc.u-tokyo.ac.jp](keisato@g.ecc.u-tokyo.ac.jp) (K.S.), [sakatsuki@cc.miyazaki-u.ac.jp](sakatsuki@cc.miyazaki-u.ac.jp) (A.S.), [takayama.kazuo@tmd.ac.jp](takayama.kazuo@tmd.ac.jp) (K.T.) In brief Immunology; Virology; Transcriptomics • OPG175 overexpression decreased MPXV infection efficiency • OPG175 knockdown increased MPXV infection efficiency • OPG175 overexpression activated Wnt signaling Nakata et al., 2025, iScience 28, 114105 December 19, 2025 © 2025 The Author(s) . Published by Elsevier Inc. [https://doi.org/10.1016/j.isci.2025.114105](https://doi.org/10.1016/j.isci.2025.114105) ll iScience ll OPEN ACCESS Article Mpox virus OPG175 negatively regulates viral replication by controlling Wnt signaling Yoshitaka Nakata,1,2 Masako Yamasaki,1 Yukio Watanabe,2 Keiya Uriu,3 Rina Hashimoto,1 Takuya Yamamoto,2,4,5 The Genotype to Phenotype Japan (G2P-Japan) Consortium, Kei Sato,3,6,7,8,9,10,11,* Akatsuki Saito,12,13,14,* and Kazuo Takayama1,2,15,* 1Department of Synthetic Human Body System, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo 113-8510, Japan 2Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan 3Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan 4Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto 606-8507, Japan 5Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8303, Japan 6Graduate School of Medicine, The University of Tokyo, Tokyo 113-8654, Japan 7Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-0882, Japan 8International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan 9International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan 10Collaboration Unit for Infection, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 860-0811, Japan 11Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand 12Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192, Japan 13Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki 889-1692, Japan 14Center for Animal Disease Control, University of Miyazaki, Miyazaki 889-2192, Japan 15Lead contact *Correspondence: [keisato@g.ecc.u-tokyo.ac.jp](keisato@g.ecc.u-tokyo.ac.jp) (K.S.), [sakatsuki@cc.miyazaki-u.ac.jp](sakatsuki@cc.miyazaki-u.ac.jp) (A.S.), [takayama.kazuo@tmd.ac.jp](takayama.kazuo@tmd.ac.jp) (K.T.) [https://doi.org/10.1016/j.isci.2025.114105](https://doi.org/10.1016/j.isci.2025.114105) SUMMARY 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 ofWnt signaling decreased MPXV replication efficiency. Therefore

FAQs

What relationship does OPG175 have with MPXV replication efficiency?

OPG175 overexpression decreases MPXV infection efficiency, while OPG175 knockdown increases infection efficiency.

Which MPXV clade shows higher OPG175 expression?

OPG175 is highly expressed in MPXV clade IIb-infected cells.

How does Wnt signaling influence MPXV replication in this study?

OPG175 overexpression enhances Wnt signaling-related gene expression, and activation of Wnt signaling decreases MPXV replication efficiency.

Sep 28, 2026

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