scholarly journals N-Terminal Domain of Borna Disease Virus G (p56) Protein Is Sufficient for Virus Receptor Recognition and Cell Entry

2001 ◽  
Vol 75 (15) ◽  
pp. 7078-7085 ◽  
Author(s):  
Mar Perez ◽  
Michiko Watanabe ◽  
Michael A. Whitt ◽  
Juan Carlos de la Torre
Keyword(s):  
Amino Acids ◽  
G Protein ◽  
Disease Virus ◽  
Fluorescent Protein ◽  
Virus Entry ◽  
Surface Glycoprotein ◽  
Terminal Part ◽  
Borna Disease Virus ◽  
Receptor Recognition ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) surface glycoprotein (GP) (p56) has a predicted molecular mass of 56 kDa. Due to extensive posttranslational glycosylation the protein migrates as a polypeptide of 84 kDa (gp84). The processing of gp84 by the cellular protease furin generates gp43, which corresponds to the C-terminal part of gp84. Both gp84 and gp43 have been implicated in viral entry involving receptor-mediated endocytosis and pH-dependent fusion. We have investigated the domains of BDV p56 involved in virus entry. For this, we used a pseudotype approach based on a recently developed recombinant vesicular stomatitis virus (VSV) in which the gene for green fluorescent protein was substituted for the VSV G protein gene (VSVΔG*). Complementation of VSVΔG* with BDV p56 resulted in infectious VSVΔG* pseudotypes that contained both BDV gp84 and gp43. BDV-VSV chimeric GPs that contained the N-terminal 244 amino acids of BDV p56 and amino acids 421 to 511 of VSV G protein were efficiently incorporated into VSVΔG* particles, and the resulting pseudotype virions were neutralized by BDV-specific antiserum. These findings indicate that the N-terminal part of BDV p56 is sufficient for receptor recognition and virus entry.

scholarly journals Characterization of Borna disease virus p56 protein, a surface glycoprotein involved in virus entry.

1997 ◽  
Vol 71 (4) ◽  
pp. 3208-3218 ◽  
Author(s):  
D Gonzalez-Dunia ◽  
B Cubitt ◽  
F A Grasser ◽  
J C de la Torre
Keyword(s):  
Disease Virus ◽  
Virus Entry ◽  
Protein A ◽  
Surface Glycoprotein ◽  
Borna Disease Virus ◽  
Borna Disease

scholarly journals Identification of Host Factors Involved in Borna Disease Virus Cell Entry through a Small Interfering RNA Functional Genetic Screen

2010 ◽  
Vol 84 (7) ◽  
pp. 3562-3575 ◽  
Author(s):  
Roberto Clemente ◽  
Eugene Sisman ◽  
Pedro Aza-Blanc ◽  
Juan C. de la Torre
Keyword(s):  
Disease Virus ◽  
Small Interfering Rna ◽  
Cell Entry ◽  
Surface Glycoprotein ◽  
Cell Tropism ◽  
Borna Disease Virus ◽  
Virus Surface ◽  
Cellular Genes ◽  
Interfering Rna ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV), the prototypic member of the Bornaviridae family, within the order Mononegavirales, is highly neurotropic and constitutes an important model system for the study of viral persistence in the central nervous system (CNS) and associated disorders. The virus surface glycoprotein (G) has been shown to direct BDV cell entry via receptor-mediated endocytosis, but the mechanisms governing cell tropism and propagation of BDV within the CNS are unknown. We developed a small interfering RNA (siRNA)-based screening to identify cellular genes and pathways that specifically contribute to BDV G-mediated cell entry. Our screen relied on silencing-mediated increased survival of cells infected with rVSVΔG*/BDVG, a cytolytic recombinant vesicular stomatitis virus expressing BDV G that mimics the cell tropism and entry pathway of bona fide BDV. We identified 24 cellular genes involved in BDV G-mediated cell entry. Identified genes are known to participate in a broad range of distinct cellular functions, revealing a complex process associated with BDV cell entry. The siRNA-based screening strategy we have developed should be applicable to identify cellular genes contributing to cell entry mediated by surface G proteins of other viruses.

scholarly journals Mechanism of Borna Disease Virus Entry into Cells

1998 ◽  
Vol 72 (1) ◽  
pp. 783-788 ◽  
Author(s):  
Daniel Gonzalez-Dunia ◽  
Beatrice Cubitt ◽  
Juan Carlos de la Torre
Keyword(s):  
Disease Virus ◽  
Virus Entry ◽  
Host Cells ◽  
Cell Surface Receptor ◽  
Animal Cells ◽  
Borna Disease Virus ◽  
C Terminus ◽  
Surface Receptor ◽  
Infected Cells ◽  
Borna Disease

ABSTRACT We have investigated the entry pathway of Borna disease virus (BDV). Virus entry was assessed by detecting early viral replication and transcription. Lysosomotropic agents (ammonium chloride, chloroquine, and amantadine), as well as energy depletion, prevented BDV infection, indicating that BDV enters host cells by endocytosis and requires an acidic intracellular compartment to allow membrane fusion and initiate infection. Consistent with this hypothesis, we observed that BDV-infected cells form extensive syncytia upon low-pH treatment. Entry of enveloped viruses into animal cells usually requires the membrane-fusing activity of viral surface glycoproteins (GPs). BDV GP is expressed as two products of 84 and 43 kDa (GP-84 and GP-43, respectively). We show here that only GP-43 is present at the surface of BDV-infected cells and therefore is likely the viral polypeptide responsible for triggering fusion events. We also present evidence that GP-43, which corresponds to the C terminus of GP-84, is generated by cleavage of GP-84 by the cellular protease furin. Hence, we propose that BDV GP-84 is involved in attachment to the cell surface receptor whereas its furin-cleaved product, GP-43, is involved in pH-dependent fusion after internalization of the virion by endocytosis.

scholarly journals Generation and Characterization of a Recombinant Vesicular Stomatitis Virus Expressing the Glycoprotein of Borna Disease Virus

2007 ◽  
Vol 81 (11) ◽  
pp. 5527-5536 ◽  
Author(s):  
Mar Perez ◽  
Roberto Clemente ◽  
Clinton S. Robison ◽  
E. Jeetendra ◽  
Himangi R. Jayakar ◽  
...  
Keyword(s):  
Disease Virus ◽  
Vesicular Stomatitis Virus ◽  
Cell Entry ◽  
Surface Glycoprotein ◽  
Free Virus ◽  
Borna Disease Virus ◽  
Virus Family ◽  
Vesicular Stomatitis ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is an enveloped virus with a nonsegmented negative-strand RNA genome whose organization is characteristic of mononegavirales. However, based on its unique genetics and biological features, BDV is considered to be the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. BDV cell entry occurs via receptor-mediated endocytosis, a process initiated by the recognition of an as yet unidentified receptor at the cell surface by the BDV surface glycoprotein (G). The paucity of cell-free virus associated with BDV infection has hindered studies aimed at the elucidation of cellular receptors and detailed mechanisms involved in BDV cell entry. To overcome this problem, we generated and characterized a replication-competent recombinant vesicular stomatitis virus expressing BDV G (rVSVΔG*/BDVG). Cells infected with rVSVΔG*/BDVG produced high titers (107 PFU/ml) of cell-free virus progeny, but this virus exhibited a highly attenuated phenotype both in cell culture and in vivo. Attenuation of rVSVΔG*/BDVG was associated with a delayed kinetics of viral RNA replication and altered genome/N mRNA ratios compared to results for rVSVΔG*/VSVG. Likewise, incorporation of BDV G into virions appeared to be restricted despite its high levels of expression and efficient processing in rVSVΔG*/BDVG-infected cells. Notably, rVSVΔG*/BDVG recreated the cell tropism and entry pathway of bona fide BDV. Our results indicate that rVSVΔG*/BDVG represents a unique tool for the investigation of BDV G-mediated cell entry, as well as the roles of BDV G in host immune responses and pathogenesis associated with BDV infection.

scholarly journals Molecular Chaperone BiP Interacts with Borna Disease Virus Glycoprotein at the Cell Surface

2009 ◽  
Vol 83 (23) ◽  
pp. 12622-12625 ◽  
Author(s):  
Tomoyuki Honda ◽  
Masayuki Horie ◽  
Takuji Daito ◽  
Kazuyoshi Ikuta ◽  
Keizo Tomonaga
Keyword(s):  
Cell Surface ◽  
Disease Virus ◽  
Molecular Chaperone ◽  
Surface Glycoprotein ◽  
Target Cells ◽  
Borna Disease Virus ◽  
Virus Surface ◽  
Chaperone Protein ◽  
Glycoprotein G ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) is characterized by highly neurotropic infection. BDV enters its target cells using virus surface glycoprotein (G), but the cellular molecules mediating this process remain to be elucidated. We demonstrate here that the N-terminal product of G, GP1, interacts with the 78-kDa chaperone protein BiP. BiP was found at the surface of BDV-permissive cells, and anti-BiP antibody reduced BDV infection as well as GP1 binding to the cell surface. We also reveal that BiP localizes at the synapse of neurons. These results indicate that BiP may participate in the cell surface association of BDV.

scholarly journals Visualizing Viral Dissemination in the Mouse Nervous System, Using a Green Fluorescent Protein-Expressing Borna Disease Virus Vector

2010 ◽  
Vol 84 (10) ◽  
pp. 5438-5442 ◽  
Author(s):  
Andreas Ackermann ◽  
Timo Guelzow ◽  
Peter Staeheli ◽  
Urs Schneider ◽  
Bernd Heimrich
Keyword(s):  
Nervous System ◽  
Green Fluorescent Protein ◽  
Disease Virus ◽  
Fluorescent Protein ◽  
Gfp Expression ◽  
Borna Disease Virus ◽  
Viral Dissemination ◽  
Viral Spread ◽  
Green Fluorescent ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) frequently persists in the brain of infected animals. To analyze viral dissemination in the mouse nervous system, we generated a mouse-adapted virus that expresses green fluorescent protein (GFP). This viral vector supported GFP expression for up to 150 days and possessed an extraordinary staining capacity, visualizing complete dendritic arbors as well as individual axonal fibers of infected neurons. GFP-positive cells were first detected in cortical areas from where the virus disseminated through the entire central nervous system (CNS). Late in infection, GFP expression was found in the sciatic nerve, demonstrating viral spread from the central to the peripheral nervous system.

scholarly journals A Borna Disease Virus Vector for Expression of Foreign Genes in Neurons of Rodents

2007 ◽  
Vol 81 (13) ◽  
pp. 7293-7296 ◽  
Author(s):  
Urs Schneider ◽  
Andreas Ackermann ◽  
Peter Staeheli
Keyword(s):  
Disease Virus ◽  
Fluorescent Protein ◽  
Foreign Gene ◽  
Borna Disease Virus ◽  
Highly Active ◽  
The Central Nervous System ◽  
Foreign Genes ◽  
Green Fluorescent ◽  
A Site ◽  
Borna Disease

ABSTRACT An expression cassette for green fluorescent protein was successfully inserted at a site near the 5′ end of the genome of Borna disease virus (BDV). When introduced into a mutant virus with highly active polymerase, the foreign gene was strongly expressed in neurons of infected rats. Since BDV can establish long-term persistence in the central nervous system of rodents, it may be used to engineer efficient vectors for specific delivery of foreign genes into highly differentiated neurons.

scholarly journals Borna Disease Virus Infection Perturbs Energy Metabolites and Amino Acids in Cultured Human Oligodendroglia Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e44665 ◽  
Author(s):  
Rongzhong Huang ◽  
Hongchang Gao ◽  
Liang Zhang ◽  
Jianmin Jia ◽  
Xia Liu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Virus Infection ◽  
Disease Virus ◽  
Borna Disease Virus ◽  
Energy Metabolites ◽  
Borna Disease

scholarly journals Two Proline-Rich Nuclear Localization Signals in the Amino- and Carboxyl-Terminal Regions of the Borna Disease Virus Phosphoprotein

1998 ◽  
Vol 72 (12) ◽  
pp. 9755-9762 ◽  
Author(s):  
Yuko Shoya ◽  
Takeshi Kobayashi ◽  
Toshiaki Koda ◽  
Kazuyoshi Ikuta ◽  
Mitsuaki Kakinuma ◽  
...  
Keyword(s):  
Amino Acids ◽  
Disease Virus ◽  
Nuclear Localization ◽  
Rna Viruses ◽  
Animal Origin ◽  
Borna Disease Virus ◽  
Nuclear Localization Signals ◽  
P Protein ◽  
Carboxyl Terminal ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV) uses a unique strategy of replication and transcription which takes place in the nucleus, unlike other known, nonsegmented, negative-stranded RNA viruses of animal origin. In this process, viral constituents necessary for replication must be transported to the nucleus from the cytoplasm. We report here the evidence that BDV P protein, which may play an important role in viral replication and transcription, is transported into the nucleus in the absence of other viral constituents. This transportation is accomplished by its own nuclear localization signals (NLSs), which are present in both N-terminal (29PRPRKIPR36) and C-terminal (181PPRIYPQLPSAPT193) regions of the protein. These two NLSs can function independently and both have several Pro residues as key amino acids.

scholarly journals Cell Entry of Borna Disease Virus Follows a Clathrin-Mediated Endocytosis Pathway That Requires Rab5 and Microtubules

2009 ◽  
Vol 83 (20) ◽  
pp. 10406-10416 ◽  
Author(s):  
Roberto Clemente ◽  
Juan C. de la Torre
Keyword(s):  
Disease Virus ◽  
Critical Role ◽  
Cell Entry ◽  
Surface Glycoprotein ◽  
Specific Cell ◽  
Critical Determinant ◽  
Borna Disease Virus ◽  
Glycoprotein G ◽  
The Central Nervous System ◽  
Borna Disease

ABSTRACT Borna disease virus (BDV), the prototypic member of the Bornaviridae family within the order Mononegavirales, exhibits high neurotropism and provides an important and unique experimental model system for studying virus-cell interactions within the central nervous system. BDV surface glycoprotein (G) plays a critical role in virus cell entry via receptor-mediated endocytosis, and therefore, G is a critical determinant of virus tissue and cell tropism. However, the specific cell pathways involved in BDV cell entry have not been determined. Here, we provide evidence that BDV uses a clathrin-mediated, caveola-independent cell entry pathway. We also show that BDV G-mediated fusion takes place at an optimal pH of 6.0 to 6.2, corresponding to an early-endosome compartment. Consistent with this finding, BDV cell entry was Rab5 dependent but Rab7 independent and exhibited rapid fusion kinetics. Our results also uncovered a key role for microtubules in BDV cell entry, whereas the integrity and dynamics of actin cytoskeleton were not required for efficient cell entry of BDV.

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