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Mouse cells expressing human intercellular adhesion molecule-1 are susceptible to infection by coxsackievirus A21
D R Shafren1, D J Dorahy, S J Greive
1Department of Microbiology, Faculty of Medicine, The University of Newcastle, New South Wales, Australia. dshafren@medicine-dmb.newcastle.ed.au
Abstract:
Competitive viral binding assays have revealed previously that coxsackievirus A21 (CAV21) and human rhinovirus 14 (HRV14) share a common cell surface receptor. More recently, intercellular adhesion molecule-1 (ICAM-1) has been identified as the cellular receptor for HRV-14. Also, anti-ICAM-1 monoclonal antibodies (MAbs) blocked infection by HRV14, CAV13, CAV18, and CAV21, suggesting that these viruses share this receptor; however, this has never been established by more direct methods. In this study we show conclusively that CAV21 binds to ICAM-1 and that MAbs directed against the N-terminal domain of the molecule inhibit this attachment. Furthermore, we show that the specific interaction between ICAM-1 and 160S CAV21 virions induces formation of 135S A particles. Finally, we show transfection of normally nonsusceptible mouse L cells with human ICAM-1 cDNA renders them susceptible to infection by CAV21.
Insights
Coxsackievirus A21 (CAV21) uses intercellular adhesion molecule-1 (ICAM-1) as its cell surface receptor. This study confirms CAV21 binds ICAM-1, enabling viral infection in previously resistant cells.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Coxsackievirus A21 (CAV21) and human rhinovirus 14 (HRV14) share a receptor.
- Intercellular adhesion molecule-1 (ICAM-1) is the receptor for HRV14.
- Monoclonal antibodies (MAbs) against ICAM-1 inhibit HRV14, CAV13, CAV18, and CAV21 infections.
Purpose of the Study:
- To conclusively establish ICAM-1 as the receptor for CAV21.
- To investigate the interaction between CAV21 and ICAM-1.
- To determine if ICAM-1 expression confers CAV21 susceptibility.
Main Methods:
- Viral binding assays using CAV21 and ICAM-1.
- Inhibition assays with anti-ICAM-1 MAbs.
- Transfection of ICAM-1 cDNA into non-susceptible cells.
Main Results:
- CAV21 directly binds to ICAM-1.
- MAbs targeting the ICAM-1 N-terminal domain block CAV21 attachment.
- CAV21-ICAM-1 interaction induces viral A particle formation.
- Transfected cells become susceptible to CAV21 infection.
Conclusions:
- ICAM-1 is the specific cellular receptor for CAV21.
- The N-terminal domain of ICAM-1 is crucial for CAV21 binding.
- ICAM-1 mediates CAV21 entry and infection.