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Updated: Jun 27, 2026
06:03
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Integrin alphaVbeta6 is a high-affinity receptor for coxsackievirus A9
Outi Heikkilä1, Petri Susi, Glyn Stanway
1Department of Virology, University of Turku, Kiinamyllynkatu 13, 20520 Turku, Finland. outi.lipiainen@utu.fi
The Journal of General Virology
|December 18, 2008
Summary
Coxsackievirus A9 uses integrins alphaVbeta3 and alphaVbeta6 for cell attachment. AlphaVbeta6 interaction is key for high-affinity binding and infectivity in lung carcinoma cells, influencing viral entry routes.
Area of Science:
- Virology
- Cell Biology
- Molecular Interactions
Background:
- Coxsackievirus A9 (CAV9), an enterovirus, has an RGD motif in its VP1 capsid protein.
- CAV9 utilizes integrins alphaVbeta3 and alphaVbeta6 for cell attachment.
- CAV9 mutants (RGE, RGDdel) show differential infectivity in A549 and RD cell lines.
Purpose of the Study:
- To analyze the relationship between CAV9 infectivity in A549 and RD cells.
- To investigate the role of integrin expression and binding in CAV9 infection.
- To understand the differential internalization routes of CAV9 and its RGDdel mutant.
Main Methods:
- Assessing integrin expression (alphaVbeta3, alphaVbeta6) on A549 and RD cells.
- Conducting binding assays with native CAV9, RGD mutants, and VP1 proteins to integrins.
- Utilizing function-blocking antibodies against alphaV-integrins.
- Performing affinity assays with soluble integrins and immobilized CAV9.
Main Results:
- A549 cells express alphaVbeta3 and alphaVbeta6; RD cells express only alphaVbeta3.
- Native CAV9 binds efficiently to alphaVbeta3 and alphaVbeta6, while mutants do not.
- CAV9 adhesion to A549 cells is higher than to RD cells.
- AlphaV-integrin blocking antibodies inhibit CAV9 but not RGDdel mutant infectivity.
- Soluble alphaVbeta6 binds to CAV9 and blocks infectivity, suggesting a high-affinity interaction.
Conclusions:
- CAV9 infectivity correlates with alphaVbeta6 expression on target cells.
- AlphaVbeta6 engagement is crucial for high-affinity CAV9 binding and potentially influences viral entry.
- Differential internalization pathways explain the distinct infectivity kinetics of CAV9 and its RGDdel mutant.
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