The Coxsackie-Adenovirus Receptor (CAR) Is Used by Reference Strains and Clinical Isolates Representing All Six Serotypes of Coxsackievirus Group B and by Swine Vesicular Disease Virus

Abstract

Group B coxsackieviruses are etiologically linked to many human diseases, and cell surface receptors are postulated to play an important role in mediating their pathogenesis. The coxsackievirus adenovirus receptor (CAR) has been shown to function as a receptor for selected strains of coxsackievirus group B (CVB) serotypes 3, 4, and 5 and is postulated to serve as a receptor for all six serotypes. In this study, we demonstrate that CAR can serve as a receptor for laboratory reference strains and clinical isolates of all six CVB serotypes. Infection of CHO cells expressing human CAR results in a 1000-fold increase in CVB progeny virus titer compared to mock transfected cells. CAR was shown to be a functional receptor for swine vesicular disease virus (SVDV), as CHO-CAR cells but not CHO mock transfected controls were susceptible to SVDV infection, produced progeny SVDV, and developed cytopathic effects. Moreover, SVDV infection could be specifically blocked by monoclonal antibody to CAR (RmcB). SVDV infection of HeLa cells was also inhibited by an anti-CD55 MAb, suggesting that this virus, like some CVB, may interact with CD55 (decay accelerating factor) in addition to CAR. Finally, pretreatment of CVB or SVDV with soluble CAR effectively blocks virus infection of HeLa cell monolayers.

Heparan sulphate mediates swine vesicular disease virus attachment to the host cell

“…Therefore, as proposed for other viruses, the binding of SVDV to cellular GAGs probably mediates an early step of the virus-cell interaction, facilitating the subsequent recognition of other receptors such as CAR (Martino et al, 2000). However, it cannot be ruled out that HS is being used as an alternative receptor.…”

“…It has been recently shown that, as in the case of coxsackievirus B1-6, the coxsackievirusadenovirus receptor (CAR) is a functional receptor for SVDV (Martino et al, 2000). Also, the decay-accelerating factor (DAF), used as co-receptor for coxsackievirus A21, B1, B3, B5, echovirus 6, 7, 11, and enterovirus 70 appears to have a role in SVDV entry into cells (Martino et al, 2000).…”

“…It has been recently shown that, as in the case of coxsackievirus B1-6, the coxsackievirusadenovirus receptor (CAR) is a functional receptor for SVDV (Martino et al, 2000). Also, the decay-accelerating factor (DAF), used as co-receptor for coxsackievirus A21, B1, B3, B5, echovirus 6, 7, 11, and enterovirus 70 appears to have a role in SVDV entry into cells (Martino et al, 2000). However, it has been shown that HS can be used as an alternative receptor for some picornaviruses, such as FMDV (Baranowski et al, 2000) and CVB3 (PD strain) (Zautner et al, 2003), in some conditions or when the 'classic' receptor is absent, a fact that supports the flexibility in picornavirus receptor usage.…”

Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells

“…It is possible that even in the presence of the antibody, other non-insulin-producing islet cells are infected with CBV-5 in a less cytolytic way. For coxsackie B viruses, two different receptors, HCAR and DAF, have been identified in established cell lines, and especially serotypes 1, 3, 5 are known to use either or both as receptors [24,25,27,52,65]. An important role of HCAR in the development of coxsackievirus diseases has been suggested in recent studies on clinical virus strains characterised after only one passage through primary green monkey kidney cells [27,65].…”

The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction

“…This disruption resulted in a decrease in the TER of the monolayers from 4,767 Ϯ 398 ⍀⅐cm 2 to 190 Ϯ 29 ⍀⅐cm 2 . EDTA was replaced with medium alone, medium containing 5 g of the hCAR extracellular domain produced as an Ig-Fc fusion protein (soluble CAR) (17), or medium containing 5 g of the avian sarcoma virus Cell Adhesion Assay. Cells were trypsinized into a single cell suspension at a concentration of 1 ϫ 10 6 cells per ml and mixed gently at room temperature for 5 h. The number of aggregated cells (Ͼ2 cells contacting each other) was determined by using a hemacytometer.…”