MOLECULAR-BASIS FOR THE DIFFERENTIAL SUBCELLULAR-LOCALIZATION OF THE 38-KILODALTON AND 39-KILODALTON STRUCTURAL PROTEINS OF BORNA-DISEASE VIRUS

Borna disease virus (BDV) is a nonsegmented negative-strand (NNS) RNA virus that is unusual because it replicates in the nucleus, The most a bundant viral protein in infected cells is a 38/39-kDa doublet that is presumed to represent the nucleocapsid, Infectious particles also con tain high levels of this protein, accounting for at least 50% of the v iral proteins. The two forms of the protein differ by an additional 13 amino acids that are present at the amino terminus of the 39-kDa form and missing from the 38-kDa form, To examine whether this difference in amino acid content affects the localization of this protein in cell s, the 39- and 38-kDa proteins were expressed in transfected cells, Th e 39-kDa form was concentrated in the nucleus, whereas the 38-kDa form was found in both the nucleus and cytoplasm, Inspection of the extra 13 amino acids present in the 39-kDa form revealed a sequence (Pro-Lys -Arg-Arg) that is very similar to the nuclear localization signals (in both sequence homology and amino-terminal location) of the VP1 protei ns of simian virus 40 and polyomavirus. Primer extension analysis of t otal RNA from infected cells suggests that there are two mRNA species encoding the two forms of the nucleocapsid protein, In infected cells, the 39-kDa form is expressed at about twofold-higher levels than the 38-kDa form at both the RNA and protein levels, The novel nuclear loca lization of the 39-kDa nucleocapsid-like protein suggests that this fo rm of the protein is targeted to the nucleus, the site for viral RNA r eplication, and that it may associate with genomic RNA.