scholarly journals The αvβ6 integrin receptor for Foot-and-mouth disease virus is expressed constitutively on the epithelial cells targeted in cattle

2005 ◽  
Vol 86 (10) ◽  
pp. 2769-2780 ◽  
Author(s):  
Paul Monaghan ◽  
Sarah Gold ◽  
Jennifer Simpson ◽  
Zhidong Zhang ◽  
Paul H. Weinreb ◽  
...  

Field strains of Foot-and-mouth disease virus (FMDV) use a number of αv-integrins as receptors to initiate infection on cultured cells, and integrins are believed to be the receptors used to target epithelial cells in animals. In this study, immunofluorescence confocal microscopy and real-time RT-PCR were used to investigate expression of two of the integrin receptors of FMDV, αvβ6 and αvβ3, within various epithelia targeted by this virus in cattle. These studies show that αvβ6 is expressed constitutively on the surfaces of epithelial cells at sites where infectious lesions occur during a natural infection, but not at sites where lesions are not normally formed. Expression of αvβ6 protein at these sites showed a good correlation with the relative abundance of β6 mRNA. In contrast, αvβ3 protein was only detected at low levels on the vasculature and not on the epithelial cells of any of the tissues investigated. Together, these data suggest that in cattle, αvβ6, rather than αvβ3, serves as the major receptor that determines the tropism of FMDV for the epithelia normally targeted by this virus.

Vaccine ◽  
2011 ◽  
Vol 29 (52) ◽  
pp. 9655-9662 ◽  
Author(s):  
Miguel A. Martín-Acebes ◽  
Ángela Vázquez-Calvo ◽  
Mónica González-Magaldi ◽  
Francisco Sobrino

2001 ◽  
Vol 75 (1) ◽  
pp. 527-532 ◽  
Author(s):  
Sherry Neff ◽  
Barry Baxt

ABSTRACT The integrin αvβ3 has been shown to function as one of the integrin receptors on cultured cells for foot-and-mouth disease virus (FMDV), and high-efficiency utilization of the bovine homolog of this integrin is dependent on the cysteine-rich repeat region of the bovine β3 subunit. In this study we have examined the role of the cytoplasmic domains of the αv and β3 subunits in FMDV infection. We have found that truncations or extensions of these domains of either subunit, including deletions removing almost all of the cytoplasmic domains, had little or no effect on the ability of the integrin to function as a receptor for FMDV. The lysosomotropic agent monensin inhibited viral replication in cells transfected with either intact or cytoplasmic domain-truncated αvβ3. In addition, viral replication in transfected cells was inhibited by an αvβ3 function-blocking antibody but not by function-blocking antibodies to three other RGD-directed integrins, suggesting that these integrins are not involved in the infectious process. These results indicate that alterations to the cytoplasmic domains of either subunit, which lead to the inability of the integrin receptor to function normally, do not abolish the ability of the integrin to bind and internalize this viral ligand.


2010 ◽  
Vol 84 (18) ◽  
pp. 9149-9160 ◽  
Author(s):  
Pradyot Dash ◽  
Paul V. Barnett ◽  
Michael S. Denyer ◽  
Terry Jackson ◽  
Catrina M. A. Stirling ◽  
...  

ABSTRACT Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin αvβ6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-β) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-β mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-α mRNA was constitutively expressed in nasal mucosal epithelial cells in vitro and in vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response.


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