The Nucleolus Is the Site of Borna Disease Virus RNA Transcription and Replication

Abstract

Borna disease virus (BDV) is a neurotropic nonsegmented negative-strand RNA virus with limited homology to rhabdoviruses and paramyxoviruses. A distinguishing feature of BDV is that it replicates in the nucleus of infected cells. Strand-specific probes used for in situ hybridization of infected rat brain showed that there was differential localization of positive- and negative-strand RNAs within the nucleus of neurons. Within nuclei, sense-strand RNAs were preferentially localized within nucleolar regions while genomic-sense RNAs were found in both nucleolar and nonnucleolar regions. These results suggested a role for the nucleolus in BDV replication. Nucleoli isolated from persistently infected neuroblastoma cells contained both genomic and antigenomic BDV RNA species as well as an enrichment of the 39/38-kDa and gp18 BDV proteins. Since the nucleolus is the site of rRNA transcription, we examined BDV transcription in the presence of inhibitors of RNA polymerase I. Inhibition of RNA polymerase I did not affect levels of BDV transcription.

Characterization of the nuclear and nucleolar localization signals of bovine herpesvirus-1 infected cell protein 27

“…Exogenous non-ribosomal proteins have been demonstrated to be transported to the nucleolus under certain conditions. Proteins from porcine reproductive and respiratory syndrome virus (Rowland et al, 1999), Semliki Forest virus (Favre et al, 1994), coronavirus (Hiscox et al, 2001), and Borna disease virus (Pyper et al, 1998) have been reported to localize in the nucleolus and be involved in various aspects of virus replication. A cluster of basic amino acids is responsible for targeting proteins to the nucleus or nucleolus (Kaffman and O'Shea, 1999).…”

Involvement of the Plant Nucleolus in Virus and Viroid Infections

“…Another animal virus, the (À)ssRNA containing Borna disease virus, uses the nucleolus as a site of genome replication (Pyper et al, 1998). An RNA-binding protein encoded by this virus has the appropriate trafficking signals for import and export to and from the nucleus (Cros and Palese, 2003)…”

Nucleolar localization of non-structural protein 3b, a protein specifically encoded by the severe acute respiratory syndrome coronavirus

“…A number of virus proteins have been shown to localize to nucleolus and dysregulated nucleolar functions for virus replication, including human immunodeficiency virus (HIV) type I Rev and Tat (Strebel, 2003), human T-cell leukemia virus (HTLV) Rex (Kubota et al, 1996), and herpes simplex virus (HSV) type 1 gamma (1) 34.5 protein (Cheng et al, 2002). The nucleolus is also the site of Borna disease virus replication and transcription (Pyper et al, 1998). Coronavirus was known to replicate and assembled in the cytoplasm.…”