Enteroviruses antagonize the host restriction factor ABL2 via proteasomal degradation to facilitate viral replication

Mengran Yuan; Xiaorong Qiao; Hua Wang; Nuo Chen; Yan Wang; Yuhan Li; Xiaoxiang Zhou; Zengjun Ji; Hongxing Shen

doi:10.1016/j.virs.2026.08.003

August 2026

. doi: 10.1016/j.virs.2026.08.003

Citation: Mengran Yuan, Xiaorong Qiao, Hua Wang, Nuo Chen, Yan Wang, Yuhan Li, Xiaoxiang Zhou, Zengjun Ji, Hongxing Shen. Enteroviruses antagonize the host restriction factor ABL2 via proteasomal degradation to facilitate viral replication .VIROLOGICA SINICA, 2026, 41(4) : 855-867. http://dx.doi.org/10.1016/j.virs.2026.08.003

肠道病毒通过蛋白酶体降解途径拮抗宿主限制因子ABL2，促进病毒复制

袁梦冉 ^a ,
谯晓容 ^a ,
王华 ^a ,
陈诺 ^a ,
王燕 ^a ,
李雨函 ^a ,
周晓翔 ^a ,
吉曾军 ^b ,
申红星 ^a,,

a 江苏大学临床医学与医学检验学院;
b 泰州市第二人民医院

通讯作者： 申红星, hxshen@ujs.edu.cn
收稿日期： 2026-03-11
录用日期： 2026-08-04

摘要

肠道病毒，包括柯萨奇病毒B3 (Coxsackievirus B3，CVB3)，是引起病毒性心肌炎、胰腺炎和脑炎等严重疾病的重要人类病原体。ABL原癌基因2 (ABL2)作为一种非受体酪氨酸蛋白激酶，调节多种生理过程并参与病毒感染；然而，其在肠道病毒感染中的作用尚不清楚。在这里，我们展示了一种新的宿主-病毒相互作用：肠道病毒通过其非结构蛋白2B，利用泛素-蛋白酶体系统降解ABL2。此外，ABL2在肠道病毒感染过程中发挥抗病毒限制因子的功能，特异性地抑制病毒复制的早期阶段。在机制上，ABL2与Rho家族GTP酶RAC1直接相互作用，并下调RAC1蛋白水平，从而抑制RAC1依赖的PI3K/Akt信号通路的激活。总之，我们的研究揭示了肠道病毒通过一种翻译后机制来逃避宿主抗病毒防御，为开发针对肠道病毒疾病的治疗方法提供了理论依据。
- 肠道病毒
- , 柯萨奇病毒B3型（CVB3）
- , 2B
- , ABL2
- , RAC1

Enteroviruses antagonize the host restriction factor ABL2 via proteasomal degradation to facilitate viral replication

a. Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Clinical Medicine & Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China;
b. Department of Laboratory Medicine, Taizhou Second People's Hospital, Taizhou 225599, China

Corresponding author: Hongxing Shen, hxshen@ujs.edu.cn
Received Date: 11 March 2026
Accepted Date: 04 August 2026

Abstract

Enteroviruses, including Coxsackievirus B3 (CVB3), are significant human pathogens that cause severe diseases, such as viral myocarditis, pancreatitis, and encephalitis. ABL proto-oncogene 2 (ABL2), a non-receptor tyrosine-protein kinase, regulates diverse physiological processes and participates in virus infection; however, its role in enterovirus infection remains uncharacterized. Here, we demonstrate a novel host-virus interaction: enteroviruses degrade ABL2 via the ubiquitin-proteasome system through their non-structural protein 2B. Furthermore, ABL2 functions as an antiviral restriction factor during enterovirus infection, specifically inhibiting the early stages of viral replication. Mechanistically, ABL2 directly interacts with RAC1, a Rho family GTPase, and downregulates RAC1 protein levels, thereby suppressing RAC1-dependent activation of the PI3K/AKT signaling pathway. In summary, our study reveals a post-translational mechanism by which enteroviruses evade host antiviral defenses, providing a rationale for therapeutic development against enteroviral diseases.
- Enterovirus
- , Coxsackievirus B3 (CVB3)
- , 2B
- , ABL2
- , RAC1

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Electronic Supplementary Material

10.1016j.virs.2026.08.003-ESM.docx