ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Virology
CBX4 facilitates EV71 replication by SUMOylation and stabilizing 3D polymerase
Rui Su
Yifan Niu
Aiping Sun
Tiesuo Zhao
Hui Wang
Henan Medical University, Xinxiang, China
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Abstract
Enterovirus 71 (EV71) is a primary etiological agent of hand-foot-mouth disease (HFMD) in children under five years of age and can cause severe neurological disorders even death. Therefore, elucidating the infection mechanism and pathogenicity of EV71 is essential for developing more effective and targeted therapies to prevent and control EV71-associated diseases. Here, we initially reported that the SUMO E3 ligase CBX4 is important for EV71 replication. Furthermore, we found that CBX4 interacts with the EV71 3D polymerase, and overexpression of CBX4 significantly extends the half-life of 3D, whereas knockdown of CBX4 reduces the stability of the 3D protein. Subsequent investigations demonstrated that CBX4 mediates both SUMOylation and ubiquitination modifications of 3D, and treatment with protein SUMOylation inhibitor 2-D08 remarkably depresses EV71 replication and the expression of ectopically transfected 3D. The regulatory role of CBX4 and the effect of 2-D08 were also observed in other enteroviruses, including coxsackievirus B3 (CVB3) and poliovirus 1 (PV1). These findings revealed that CBX4 facilitates EV71 infection through inducing SUMOylation and stabilization of 3D polymerase, hinting its potential as a novel target for antiviral development.
Summary
Keywords
3D polymerase, CBX4, enterovirus 71, protein stabilization, Sumoylation
Received
26 December 2025
Accepted
17 February 2026
Copyright
© 2026 Su, Niu, Sun, Zhao and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hui Wang
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