THE GLYCOSYLATED MATRIX PROTEIN OF BORNA-DISEASE VIRUS IS A TETRAMERIC MEMBRANE-BOUND VIRAL COMPONENT ESSENTIAL FOR INFECTION

Borna disease virus (BDV) is representative of the family of Bornaviri dae in the order Mononegavirales (negative-stranded, non-segmented, en veloped RNA viruses). It is the causal agent for Borna disease, charac terized as an encephalomyelitis (typical form) in a wide variety of do mestic animals (from rodents to birds). Recent information shows the i nvolvement of BDV in the pathogenesis of some human psychiatric disord ers. The 8.9-kb viral antigenome codes for five major ORE The third OR F codes for a 16-kDa protein (matrix protein) that is posttranslationa lly modified, yielding an N-linked glycoprotein. Our data show that th e glycosylated matrix protein exists as a stable tetrameric structure detectable either by electrospray ionization or matrix-assisted laser- desorption ionization mass spectrometry. Under native conditions, the tetramer, with a relative molecular mass of 68 kDa, was isolated from a sediment-free brain suspension of a BDV-infected horse. The 68-kDa e ntity is stable in the presence of ionic and nonionic detergents but d issociates into subunits when heated. We found that the tetrameric mat rix protein inhibits in vitro BDV infection in a dose-dependent manner . In contrast to inhibition of BDV infection with hydrophobic carbohyd rate derivatives and protein-bound glycoconjugates, the glycosylated m atrix protein is a very potent inhibitor of BDV infection, indicating that this protein represents an essential virus-specific membrane comp onent for viral attachment.