CHARACTERIZATION OF BORNA-DISEASE VIRUS P56 PROTEIN, A SURFACE GLYCOPROTEIN INVOLVED IN VIRUS ENTRY

Borna disease virus (BDV) is a nonsegmented negative-stranded (NNS) RN A virus, prototype of a new taxon in the Mononegavirales order. BDV ca uses neurologic disease manifested by behavioral abnormalities in seve ral animal species, and evidence suggests that it may be a human patho gen. To improve our knowledge about the biology of this novel virus, w e have identified and characterized the product of BDV open reading fr ame IV (BVp56). Based on sequence features, BVp56 encodes a virus surf ace glycoprotein. Glycoproteins play essential roles in the biology of NNS RNA viruses. Expression of BVp56 resulted in the generation of tw o polypeptides with molecular masses of about 84 and 43 kDa (GP-84 and GP-43). GP-84 and GP-43 likely correspond to the full length BVp56 ge ne and to its C terminus, respectively. Endoglycosidase studies demons trated that both products were glycosylated and that this process was required for the stabilization of newly synthesized products. Moreover , our results suggested that GP-43 is generated by cleavage of GP-84 b y a cellular protease. Subcellular localization studies demonstrated t hat GP-84 accumulates in the ER, whereas GP-43 reaches the cell surfac e. Both BVp56 products were found to be associated crith infectious vi rions, and antibodies to BVp56 had neutralizing activity. Our findings suggest that BVp56 exhibits a novel form of processing for an animal NNS RNA virus surface glycoprotein, which might influence the assembly and budding of BDV.