Junctional Adhesion Molecule 1 Is a Functional Receptor for Feline Calicivirus

Abstract

The life cycle of calicivirus is not fully understood because most of the viruses cannot be propagated in tissue culture cells. We studied the mechanism of calicivirus entry into cells using feline calicivirus (FCV) The family Caliciviridae comprises a diversity of pathogens in humans and animals. Studies of the life cycle of the virus have been quite limited because of the lack of cell culture methods for most caliciviruses (13). Porcine enteric calicivirus in the genus Sapovirus is known to propagate in vitro with the addition of an intestinal content fluid filtrate, and Chang et al. (6) recently identified bile acids as molecules responsible for culture in cells. Studies with virus-like particles showed that ABH histo-blood group antigens are ligands of noroviruses belonging to the genus Norovirus (24). Studies in vivo also showed that these antigens are critical for human susceptibility to norovirus infection (17,22). Because noroviruses are not cultivable in cell culture (9), it has not been established whether ABH histo-blood antigens function as receptors for them.,Feline calicivirus (FCV) is a member of the genus Vesivirus and causes upper respiratory tract disease and acute mouth ulceration, occasionally associated with chronic stomatitis and acute arthritis in cats (15,21). It is comparatively easy to study the life cycle of FCV, because the virus replicates efficiently in cell culture without specific supplementation. Kreutz et al. (20) investigated the binding of FCV to feline and nonfeline cells.They reported that FCV bound to feline cells but also showed poor binding ability to nonfeline cells. It was also demonstrated that when nonfeline cells were transfected with genomic RNA of FCV, infectious virus could be recovered from the cells (20). These data suggest that FCV host specificity is restricted in the early stage of FCV infection in cells.In this study, to elucidate the cellular determinant(s) of FCV host specificity, we applied an improved expression cloning method (28,29) to identify cell surface molecules that interact with FCV. As a result, feline junctional adhesion molecule 1 (JAM-1) was identified as a binding receptor for FCV. JAM-1 is a member of the immunoglobulin (Ig) superfamily expressed by various cells and is involved in regulation of cell-cell interactions in the immune system and apical tight junction formation (10, 23). We here demonstrate that feline JAM-1 (fJAM-1) possesses the characteristics required of a functional receptor for FCV. MATERIALS AND METHODS Cells.Crandell-Rees feline kidney (CRFK) cells and human embryonic kidney 293T cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Sigma, St. Louis, MO) supplemented with 10% fetal calf serum (FCS). Nonpermissive hamster lung (HmLu-1) cells and African green monkey kidney (Vero) cells were cultured in DMEM with 5% FCS. Murine myeloma P3X63Ag8U.1 (P3U1) cells were grown in RPMI 1640 medium (Sigma) with 10% FCS. Plat-E cells, a 293T-derived murine leukemia virus-based packaging cell line (25), were kindly pr...

Feline calicivirus

“…A big break through for FCV research was recently reported when the junctional adhesion molecule-1 (JAM-1) was identified as a cellular receptor for FCV in cell culture [62]. Transfection of nonpermissive cells with a JAM-1 expression system rendered the cell line permissive for FCV and anti-feline JAM-1 antibodies reduced replication of FCV in permissive cells.…”

The Cryo-Electron Microscopy Structure of Feline Calicivirus Bound to Junctional Adhesion Molecule A at 9-Angstrom Resolution Reveals Receptor-Induced Flexibility and Two Distinct Conformational Changes in the Capsid Protein VP1

“…Ossiboff and Parker have identified three amino acid residues, mutation of which led to reductions in binding to FCV strain 5: D42, K43, and S97 (18). In their initial study describing fJAM-A as the functional receptor for FCV, Makino et al (15) proposed that S91 and K155 may also be important, following comparison of sequences for fJAM-A and simian JAM-A (which bind FCV) with human JAM-A (which does not). Of these residues, only K155 is not close to or part of the footprint we have identified through our fitting experiments (Fig.…”

“…FCV is arguably the best characterized of these and to date is the only calicivirus for which a protein receptor has been identified. FCV binds to ␣-2,6-sialic acid and to feline junctional adhesion molecule A (fJAM-A, also known as fJAM-1) (15,25). Transfection of fJAM-A into nonpermissive cells renders them susceptible to FCV infection, while antibodies directed against fJAM-A can be used to inhibit FCV entry.…”

Targeting Norovirus: Strategies for the Discovery of New Antiviral Drugs

“…Recent findings of FCV and MNV binding to sialic acid (Rydell et al, 2009;Stuart & Brown, 2007;Taube et al, 2009) or heparan sulfate (Tamura et al, 2004) broadens the spectrum of sugar residues that interact with these viruses. Moreover, the identification of a membrane protein, the junctional adhesion molecule A (JAM-A), as a receptor for FCV (Makino et al, 2006) raises the hypothesis of this protein or other members of the Ig superfamily being also cellular receptors for caliciviruses, like they are for reoviruses and picornaviruses (Tan & Jiang, 2010). According to the proposed model for reoviruses, the virus interact firstly with a sugar residue like sialic acid, as a determinant of tropism that is responsible for initial virus attachment, and later use a membrane protein (JAM-1) to enter the host cell (Barton et al, 2001).…”