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

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

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

Mengran Yuan ^a ,
Xiaorong Qiao ^a ,
Hua Wang ^a ,
Nuo Chen ^a ,
Yan Wang ^a ,
Yuhan Li ^a ,
Xiaoxiang Zhou ^a ,
Zengjun Ji ^b ,
Hongxing Shen ^{a
,,}

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
Available online: 11 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

Electronic Supplementary Material

10.1016j.virs.2026.08.003-ESM.docx
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