scholarly journals Authentic Borna disease virus transcripts are spliced less efficiently than cDNA-derived viral RNAs

2000 ◽  
Vol 81 (8) ◽  
pp. 1947-1954 ◽  
Author(s):  
Christian Jehle ◽  
W. Ian Lipkin ◽  
Peter Staeheli ◽  
Rosa M. Marion ◽  
Martin Schwemmle
Keyword(s):  
Disease Virus ◽  
Rna Virus ◽  
Borna Disease Virus ◽  
Viral Rnas ◽  
Negative Strand ◽  
Intron 1 ◽  
Splicing Pattern ◽  
Alternatively Spliced ◽  
Infected Cells ◽  
Borna Disease

Borna disease virus (BDV) is a non-segmented, negative-strand RNA virus that replicates and transcribes its genome in the nucleus of infected cells. It uses the cellular splicing machinery to generate a set of alternatively spliced mRNAs from the 2·8 and 7·1 kb primary transcripts, each harbouring two introns. To determine whether splicing of these transcripts is regulated by viral factors, the extent of splicing was studied in infected cells and COS-7 cells transiently transfected with plasmids encoding the 2·8 kb RNA of BDV. Unspliced RNA was found to be the most abundant RNA species in infected cells, whereas viral transcripts lacking both introns were only found in minute amounts. In sharp contrast, plasmid-derived 2·8 kb RNA was predominantly intron 1-spliced and double-spliced. Co-expression of the BDV proteins P, N and X did not influence splicing of plasmid-expressed 2·8 kb RNA. Furthermore, the splicing pattern did not change when the 2·8 kb RNA was expressed in BDV-infected cells. Based on these results we speculate that splicing of authentic BDV transcripts is tightly linked to transcription by the viral polymerase.

scholarly journals Modulation of Borna Disease Virus Phosphoprotein Nuclear Localization by the Viral Protein X Encoded in the Overlapping Open Reading Frame

2003 ◽  
Vol 77 (14) ◽  
pp. 8099-8107 ◽  
Author(s):  
Takeshi Kobayashi ◽  
Guoqi Zhang ◽  
Byeong-Jae Lee ◽  
Satoko Baba ◽  
Makiko Yamashita ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Disease Virus ◽  
Viral Protein ◽  
Rna Virus ◽  
Viral Proteins ◽  
Borna Disease Virus ◽  
Negative Strand ◽  
Intracellular Movement ◽  
Infected Cells ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the Mononegavirales order. Unlike other animal viruses in this order, BDV replicates and transcribes in the nucleus of infected cells. Therefore, regulation of the intracellular movement of virus components must be critical for accomplishing the BDV life cycle in mammalian cells. Previous studies have demonstrated that BDV proteins are prone to accumulate in the nucleus of cells transiently transfected with each expression plasmid of the viral proteins. In BDV infection, however, cytoplasmic distribution of the viral proteins is frequently found in cultured cells and animal brains. In this study, to understand the modulation of subcellular localization of BDV proteins, we investigated the intracellular localization of the viral phosphoprotein (P). Transient-transfection analysis with a cDNA clone corresponding to a bicistronic transcript that expresses both viral X and P revealed that P efficiently localizes in the cytoplasm only when BDV X is expressed in the cells. Furthermore, our analysis revealed that the direct binding between X and P is necessary for the cytoplasmic localization of the P. Interestingly, we showed that X is not detectably expressed in the BDV-infected cells in which P is predominantly found in the nucleus, with little or no signal in the cytoplasm. These observations suggested that BDV P can modulate their subcellular localization through binding to X and that BDV may regulate the expression ratio of each viral product in infected cells to control the intracellular movement of the viral protein complexes. The results presented here provide a new insight into the regulation of the intracellular movement of viral proteins of a unique, nonsegmented, negative-strand RNA virus.

scholarly journals Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells.

1992 ◽  
Vol 89 (23) ◽  
pp. 11486-11489 ◽  
Author(s):  
T. Briese ◽  
J. C. de la Torre ◽  
A. Lewis ◽  
H. Ludwig ◽  
W. I. Lipkin
Keyword(s):  
Disease Virus ◽  
Rna Virus ◽  
Borna Disease Virus ◽  
Negative Strand ◽  
Infected Cells ◽  
Borna Disease

scholarly journals 1-β-d-Arabinofuranosylcytosine Inhibits Borna Disease Virus Replication and Spread

2002 ◽  
Vol 76 (12) ◽  
pp. 6268-6276 ◽  
Author(s):  
Jeffrey J. Bajramovic ◽  
Sylvie Syan ◽  
Michel Brahic ◽  
Juan Carlos de la Torre ◽  
Daniel Gonzalez-Dunia
Keyword(s):  
Disease Virus ◽  
Measles Virus ◽  
Rna Virus ◽  
Neurological Diseases ◽  
Borna Disease Virus ◽  
Negative Strand ◽  
Neuropsychiatric Diseases ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that causes neurological diseases in a variety of warm-blooded animal species. There is general consensus that BDV can also infect humans, being a possible zoonosis. Although the clinical consequences of human BDV infection are still controversial, experimental BDV infection is a well-described model for human neuropsychiatric diseases. To date, there is no effective treatment against BDV. In this paper, we demonstrate that the nucleoside analog 1-β-d-arabinofuranosylcytosine (Ara-C), a known inhibitor of DNA polymerases, inhibits BDV replication. Ara-C treatment inhibited BDV RNA and protein synthesis and prevented BDV cell-to-cell spread in vitro. Replication of other negative-strand RNA viruses such as influenza virus or measles virus was not inhibited by Ara-C, underscoring the particularity of the replication machinery of BDV. Strikingly, Ara-C treatment induced nuclear retention of viral ribonucleoparticles. These findings could not be attributed to known effects of Ara-C on the host cell, suggesting that Ara-C directly inhibits the BDV polymerase. Finally, we show that Ara-C inhibits BDV replication in vivo in the brain of infected rats, preventing persistent infection of the central nervous system as well as the development of clinical disease. These findings open the way to the development of effective antiviral therapy against BDV.

scholarly journals Characterization of the Nuclear Localization Signal of the Borna Disease Virus Polymerase

2002 ◽  
Vol 76 (16) ◽  
pp. 8460-8467 ◽  
Author(s):  
Michelle Portlance Walker ◽  
W. Ian Lipkin
Keyword(s):  
Disease Virus ◽  
Nuclear Localization ◽  
Nuclear Localization Signal ◽  
Rna Virus ◽  
Flag Epitope ◽  
Borna Disease Virus ◽  
Localization Signal ◽  
Infected Cells ◽  
Pass Through ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is a nonsegmented negative-strand RNA virus that replicates and transcribes its genome in the nucleus of infected cells. BDV proteins involved in replication and transcription must pass through the nuclear envelope to associate with the genomic viral RNA. The RNA-dependent RNA polymerase (L) of BDV is postulated to be the catalytic enzyme of replication and transcription. We demonstrated previously that BDV L localizes to the nucleus of BDV-infected cells and L-transfected cells. Nuclear localization of the protein presupposes the presence of a nuclear localization signal (NLS) within its primary amino acid sequence or cotransport to the nucleus with another karyophilic protein. Because L localized to the nucleus in the absence of other viral proteins, we investigated the possibility that L contains an NLS. The minimal sequence required for nuclear localization of L was identified by analyzing the subcellular distribution of deletion mutants of L fused to a flag epitope tag or β-galactosidase. Although the majority of the L fusion proteins localized to the cytoplasm of transfected BSR-T7 cells, a strong NLS (844RVVKLRIAP852) with basic and proline residues was identified. Mutation of this sequence resulted in cytoplasmic distribution of L, confirming that this sequence was necessary and sufficient to drive the nuclear localization of L.

RNA splicing contributes to the generation of mature mRNAs of Borna disease virus, a non-segmented negative strand RNA virus

1994 ◽  
Vol 34 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Beatrice Cubitt ◽  
Christopher Oldstone ◽  
Juan Valcarcel ◽  
Juan Carlos de la Torre
Keyword(s):  
Disease Virus ◽  
Rna Splicing ◽  
Rna Virus ◽  
Borna Disease Virus ◽  
Negative Strand ◽  
Mature Mrnas ◽  
Borna Disease

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

1998 ◽  
Vol 72 (9) ◽  
pp. 7697-7702 ◽  
Author(s):  
J. M. Pyper ◽  
J. E. Clements ◽  
M. C. Zink
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Rna Virus ◽  
Neuroblastoma Cells ◽  
Rna Polymerase I ◽  
Borna Disease Virus ◽  
Negative Strand ◽  
Sense Strand ◽  
Polymerase I ◽  
Borna Disease

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.

scholarly journals RNA splicing in Borna disease virus, a nonsegmented, negative-strand RNA virus.

1994 ◽  
Vol 68 (8) ◽  
pp. 5007-5012 ◽  
Author(s):  
P A Schneider ◽  
A Schneemann ◽  
W I Lipkin
Keyword(s):  
Disease Virus ◽  
Rna Splicing ◽  
Rna Virus ◽  
Borna Disease Virus ◽  
Negative Strand ◽  
Borna Disease
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