scholarly journals Fine Structure and Morphogenesis of Borna Disease Virus

1999 ◽  
Vol 73 (1) ◽  
pp. 760-766 ◽  
Author(s):  
Takehiro Kohno ◽  
Toshiyuki Goto ◽  
Tomohiko Takasaki ◽  
Chizuko Morita ◽  
Takaaki Nakaya ◽  
...  
Keyword(s):  
Fine Structure ◽  
Cell Surface ◽  
Disease Virus ◽  
Mdck Cells ◽  
Rna Virus ◽  
Borna Disease Virus ◽  
Persistently Infected ◽  
Virus Like Particles ◽  
Hemagglutinating Virus ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV), a negative nonsegmented single-stranded RNA virus, has not been fully characterized morphologically. Here we present what is to our knowledge the first data on the fine ultrastructure and morphogenesis of BDV. The supernatant of MDCK cells persistently infected with BDV treated with n-butyrate contained many virus-like particles and more BDV-specific RNA than that of untreated samples. The particles were spherical, enveloped, and approximately 130 nm in diameter; had spikes 7 nm in length; and reacted with BDV p40 antibody. A thin nucleocapsid, 4 nm in width, was present peripherally in contrast to the thick nucleocapsid of hemagglutinating virus of Japan. The BDV particles reproduced by budding on the cell surface.

scholarly journals Virus-like particles in MDCK cells persistently infected with Borna disease virus

1994 ◽  
Vol 33 (3) ◽  
pp. 261-268 ◽  
Author(s):  
Richard W. Compans ◽  
Lawrence R. Melsen ◽  
Juan Carlos de la Torre
Keyword(s):  
Disease Virus ◽  
Mdck Cells ◽  
Borna Disease Virus ◽  
Persistently Infected ◽  
Virus Like Particles ◽  
Borna Disease

scholarly journals Protein X of Borna Disease Virus Inhibits Apoptosis and Promotes Viral Persistence in the Central Nervous Systems of Newborn-Infected Rats

2009 ◽  
Vol 83 (9) ◽  
pp. 4297-4307 ◽  
Author(s):  
Marion Poenisch ◽  
Nils Burger ◽  
Peter Staeheli ◽  
Georg Bauer ◽  
Urs Schneider
Keyword(s):  
Disease Virus ◽  
Cultured Cells ◽  
Rna Virus ◽  
Viral Persistence ◽  
Apoptosis Induction ◽  
Wild Type ◽  
Borna Disease Virus ◽  
Persistently Infected ◽  
Protein X ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is a neurotropic member of the order Mononegavirales with noncytolytic replication and obligatory persistence in cultured cells and animals. Here we show that the accessory protein X of BDV represents the first mitochondrion-localized protein of an RNA virus that inhibits rather than promotes apoptosis induction. Rat C6 astroglioma cells persistently infected with wild-type BDV were significantly more resistant to death receptor-dependent and -independent apoptotic stimuli than uninfected cells or cells infected with a BDV mutant expressing reduced amounts of X. Confocal microscopy demonstrated that X colocalizes with mitochondria and expression of X from plasmid DNA rendered human 293T and mouse L929 cells resistant to apoptosis induction. A recombinant virus encoding a mutant X protein unable to associate with mitochondria (BDV-XA6A7) failed to block apoptosis in C6 cells. Furthermore, Lewis rats neonatally infected with BDV-XA6A7 developed severe neurological symptoms and died around day 30 postinfection, whereas all animals infected with wild-type BDV remained healthy and became persistently infected. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining revealed a significant increase in the number of apoptotic cells in the brain of BDV-XA6A7-infected animals, whereas the numbers of CD3+ T lymphocytes were comparable to those detected in animals infected with wild-type BDV. Our data thus indicate that inhibition of apoptosis by X promotes noncytolytic viral persistence and is required for the survival of cells in the central nervous system of BDV-infected animals.

scholarly journals Borna Disease Virus Phosphoprotein Represses p53-Mediated Transcriptional Activity by Interference with HMGB1

2003 ◽  
Vol 77 (22) ◽  
pp. 12243-12251 ◽  
Author(s):  
Guoqi Zhang ◽  
Takeshi Kobayashi ◽  
Wataru Kamitani ◽  
Satoshi Komoto ◽  
Makiko Yamashita ◽  
...  
Keyword(s):  
Disease Virus ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Rna Virus ◽  
Broad Host Range ◽  
Neural Cells ◽  
Cellular Functions ◽  
Borna Disease Virus ◽  
Multifunctional Protein ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that has a broad host range in warm-blooded animals, probably including humans. Recently, it was demonstrated that a 24-kDa phosphoprotein (P) of BDV directly binds to a multifunctional protein, amphoterin-HMGB1, and inhibits its function in cultured neural cells (W. Kamitani, Y. Shoya, T. Kobayashi, M. Watanabe, B. J. Lee, G. Zhang, K. Tomonaga, and K. Ikuta, J. Virol. 75:8742-8751, 2001). This observation suggested that expression of BDV P may cause deleterious effects in cellular functions by interference with HMGB1. In this study, we further investigated the significance of the binding between P and HMGB1. We demonstrated that P directly binds to the A-box domain on HMGB1, which is also responsible for interaction with a tumor suppression factor, p53. Recent works have demonstrated that binding between HMGB1 and p53 enhances p53-mediated transcriptional activity. Thus, we examined whether BDV P affects the transcriptional activity of p53 by interference with HMGB1. Mammalian two-hybrid analysis revealed that p53 and P competitively interfere with the binding of each protein to HMGB1 in a p53-deficient cell line, NCI-H1299. In addition, P was able to significantly decrease p53-mediated transcriptional activation of the cyclin G promoter. Furthermore, we showed that activation of p21waf1 expression was repressed in cyclosporine-treated BDV-infected cells, as well as p53-transduced NCI-H1299 cells. These results suggested that BDV P may be a unique inhibitor of p53 activity via binding to HMGB1.

scholarly journals Downregulation of an Astrocyte-Derived Inflammatory Protein, S100B, Reduces Vascular Inflammatory Responses in Brains Persistently Infected with Borna Disease Virus

2007 ◽  
Vol 81 (11) ◽  
pp. 5940-5948 ◽  
Author(s):  
Naohiro Ohtaki ◽  
Wataru Kamitani ◽  
Yohei Watanabe ◽  
Yohei Hayashi ◽  
Hideyuki Yanai ◽  
...  
Keyword(s):  
Disease Virus ◽  
Persistent Infection ◽  
Immune Modulation ◽  
Inflammatory Responses ◽  
Borna Disease Virus ◽  
Persistently Infected ◽  
Inflammatory Protein ◽  
Inflammatory Stimuli ◽  
Protein Immunoreactivity ◽  
Borna Disease

ABSTRACTBorna disease virus (BDV) is a neurotropic virus that causes a persistent infection in the central nervous system (CNS) of many vertebrate species. Although a severe reactive gliosis is observed in experimentally BDV-infected rat brains, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this regard, we examined the expression of an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. S100B is a Ca2+-binding protein produced mainly by astrocytes. A prominent role of this protein appears to be the promotion of vascular inflammatory responses through interaction with the receptor for advanced glycation end products (RAGE). Here we show that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even when incited with several inflammatory stimuli, including lipopolysaccharide. In addition, expression of the vascular cell adhesion molecule 1 (VCAM-1), as well as the infiltration of encephalitogenic T cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S100B in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection.

scholarly journals Rat Model of Borna Disease Virus Transmission: Epidemiological Implications

2003 ◽  
Vol 77 (23) ◽  
pp. 12886-12890 ◽  
Author(s):  
Christian Sauder ◽  
Peter Staeheli
Keyword(s):  
Disease Virus ◽  
Rat Model ◽  
Infectious Virus ◽  
Virus Transmission ◽  
Farm Animals ◽  
Borna Disease Virus ◽  
Persistently Infected ◽  
Rapid Transmission ◽  
Fresh Urine ◽  
Borna Disease

ABSTRACT Rapid transmission of Borna disease virus occurred upon cohabitation of persistently infected and naive rats. Infectious virus, which was abundantly present in fresh urine samples of carrier rats, entered the brains of recipient rats via the olfactory route. Thus, susceptible farm animals possibly acquire the virus from persistently infected rats.

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 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 Evidence of Borna disease virus genome detection in French domestic animals and in foxes (Vulpes vulpes)

2001 ◽  
Vol 82 (9) ◽  
pp. 2199-2204 ◽  
Author(s):  
G. Dauphin ◽  
V. Legay ◽  
C. Sailleau ◽  
S. Smondack ◽  
S. Hammoumi ◽  
...  
Keyword(s):  
Disease Virus ◽  
Roe Deer ◽  
Rna Virus ◽  
Internal Standard ◽  
Virus Genome ◽  
Red Foxes ◽  
Borna Disease Virus ◽  
Blood Samples ◽  
Horse Blood ◽  
Borna Disease

Borna disease virus (BDV) is an enveloped, non-segmented negative-stranded RNA virus which belongs to the Bornaviridae family. BDV is an aetiological agent of encephalitis in horses, sheep and several other vertebrate species. In order to extend our knowledge about the presence of BDV in France, a study based on BDV RNA detection by RT–nested-PCR was done with 196 animal tissues: 171 brain samples collected from different animal species (75 horses, 59 foxes, 31 cattle, 4 dogs, 1 sheep, 1 roe deer) and 25 horse blood samples. An RNA internal standard molecule was constructed and was co-amplified with the test template. This study reports the first detection of BDV RNA in France in 10 brain samples collected from horses, foxes and cattle, and from 14 horse blood samples. Detection of the BDV genome in the brains of six red foxes is the first evidence of BDV infection in this species.

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