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The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus
T Jackson1, D Sheppard, M Denyer
1Department of Molecular Biology, Institute for Animal Health, Pirbright, Surrey GU24 ONF, United Kingdom. terry.jackson@bbsrc.ac.uk
Abstract:
Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin alphavbeta3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, alphavbeta6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin beta6 subunit and expression of alphavbeta6 at the cell surface. Integrin alphavbeta6 is the major site for virus attachment on the beta6-transfected cells, and binding to alphavbeta6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the beta6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes alphavbeta6. These studies establish a role for alphavbeta6 as a cellular receptor for FMDV.
Insights
Foot-and-mouth disease virus (FMDV) uses integrin alphavbeta6 as a cellular receptor. This discovery in epithelial cells advances understanding of FMDV infection mechanisms and potential therapeutic targets.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Foot-and-mouth disease virus (FMDV) utilizes RGD-dependent integrins for cellular entry.
- Integrin alphavbeta3 is a known FMDV receptor on cultured cells.
- Integrin alphavbeta6, expressed on epithelial cells, is a potential in vivo receptor due to viral tissue tropism.
Purpose of the Study:
- To investigate the role of integrin alphavbeta6 as a cellular receptor for FMDV.
- To determine if alphavbeta6 expression can render nonpermissive cells susceptible to FMDV infection.
- To elucidate the mechanism of FMDV binding and entry via alphavbeta6.
Main Methods:
- Transfection of SW480 cells with the integrin beta6 subunit to express alphavbeta6.
- Assessing FMDV attachment, entry, and infection in beta6-transfected cells.
- Utilizing a monoclonal antibody (10D5) against alphavbeta6 to inhibit virus binding and infection.
Main Results:
- SW480 cells expressing alphavbeta6 became susceptible to FMDV infection.
- Integrin alphavbeta6 was identified as the primary site for FMDV attachment and increased viral entry.
- FMDV binding and infection were mediated by an RGD-dependent interaction specifically inhibited by anti-alphavbeta6 antibody.
Conclusions:
- Integrin alphavbeta6 functions as a cellular receptor for FMDV.
- Expression of alphavbeta6 confers susceptibility to FMDV infection in previously nonpermissive cells.
- The RGD motif on FMDV interacts with alphavbeta6, mediating viral attachment and entry.