Characterization of the Epstein–Barr virus glycoprotein BMRF-2

Epstein–Barr virus (EBV) BMRF-2 protein interaction with the β1 family of integrins plays an important role in EBV infection of polarized oral epithelial cells. In this work, we characterized BMRF-2 protein expression in EBV-infected B lymphoblastoid and polarized oral epithelial cells, and in hairy leukoplakia (HL) epithelium. BMRF-2 expression in B cells and polarized oral epithelial cells was associated with the EBV lytic infection. In these cells, BMRF-2 is efficiently transported to the cell membrane and its integrin binding Arg–Gly–Asp (RGD) motif is exposed on the cell surface. BMRF-2 is highly expressed in HL epithelium and accumulates at the lateral border of oral keratinocytes. In EBV-infected polarized oral epithelial cells, this protein is transported to the basolateral membranes and co-localized with β1 integrin. These data suggest that BMRF-2 may play an important role in cell-to-cell spread of EBV within the oral epithelium. BMRF-2 is glycosylated through O-linked oligosaccharides; it forms oligomers and is associated with the virion envelope. Its C-terminal tail is localized in the cytoplasm. We found that β1, α5, and α3 integrins are present in purified EBV virions. We show that BMRF-2 is a ligand for β1, α5, α3, and αv integrins and our data are consistent with a role for BMRF-2 in viral lytic infection.