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Updated: Aug 13, 2026

Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Enteroviruses antagonize the host restriction factor ABL2 via proteasomal degradation to facilitate viral replication
Mengran Yuan1, Xiaorong Qiao1, Hua Wang1
1Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Laboratory Medicine, School of Clinical Medicine & Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
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.
Insights
Enteroviruses degrade the host protein ABL2 (Abelson murine leukemia 1-2) to promote infection. ABL2 acts as a restriction factor, inhibiting viral replication by downregulating RAC1 and the PI3K/AKT pathway.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Enteroviruses, such as Coxsackievirus B3 (CVB3), are major human pathogens causing severe diseases.
- The role of ABL proto-oncogene 2 (ABL2) in enterovirus infection was previously unknown.
Purpose of the Study:
- To investigate the interaction between enteroviruses and ABL2.
- To elucidate the function of ABL2 in enterovirus infection and its underlying mechanism.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- Western blotting to assess protein degradation and levels.
- Analysis of viral replication in the presence and absence of ABL2.
Main Results:
- Enteroviruses degrade host ABL2 via the ubiquitin-proteasome pathway mediated by viral protein 2B.
- ABL2 functions as an antiviral restriction factor, inhibiting early viral replication.
- ABL2 interacts with RAC1, downregulating its levels and suppressing the PI3K/AKT signaling pathway.
Conclusions:
- Enteroviruses employ a post-translational mechanism to degrade ABL2, thereby evading host antiviral defenses.
- ABL2's interaction with RAC1 and subsequent pathway modulation highlights a novel host-virus interplay.
- Understanding this interaction provides a basis for developing new therapeutics against enteroviral diseases.
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