Borna disease virus-specific antigens: two different proteins identified by monoclonal antibodies

Bause-Niedrig, Ingrid; Pauli, Georg; Ludwig, Hanns

doi:10.1016/0165-2427(91)90027-a

Cited by 23 publications

(13 citation statements)

References 16 publications

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“…Previous studies have demonstrated that BDV p24 protein is a major product among the viral proteins, and it is always detected in BDV-infected cultured cells and rat brain cells (2,3). These observations suggest a possibility that BDV p24 may directly alter the host cell environments by binding to host cellular factor(s).…”

Section: Bdv P24 Phosphoprotein Binds a 30-kda Proteinmentioning

confidence: 64%

“…The p24 phosphoprotein of BDV is an abundant protein in infected cultured cells and in infected animal brains (2,3). Although the precise role of the protein in the viral life cycle has not yet been determined, it is assumed that the protein associates and cooperates with the pol protein to play a pivotal role in viral transcription and replication in the nucleus (26,48).…”

Section: Discussionmentioning

confidence: 99%

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Borna Disease Virus Phosphoprotein Binds a Neurite Outgrowth Factor, Amphoterin/HMG-1

Kamitani

Shoya

Kobayashi

et al. 2001

J Virol

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The Borna disease virus (BDV) p24 phosphoprotein is an abundant protein in BDV-infected cultured cells and animal brains. Therefore, there is a possibility that binding of the p24 protein to cellular factor(s) induces functional alterations of infected neural cells in the brain. To identify a cellular protein(s) that interacts with BDV p24 protein, we performed far-Western blotting with extracts from various cell lines. Using recombinant p24 protein as a probe, we detected a 30-kDa protein in all cell lines examined. Binding between the 30-kDa and BDV p24 proteins was also demonstrated using BDV p24 affinity and ion-exchange chromatography columns. Microsequence analysis of the purified 30-kDa protein revealed that its N terminus showed complete homology with rat amphoterin protein, which is a neurite outgrowth factor abundant in the brain during development. Mammalian two-hybrid and immunoprecipitation analyses also confirmed that amphoterin is a specific target for the p24 protein in vivo. Furthermore, we showed that infection by BDV, as well as purified p24 protein in the medium, significantly decreased cell process outgrowth of cells grown on laminin, indicating the functional inhibition of amphoterin by interaction with the p24 protein. Immunohistochemical analysis revealed decreased levels of amphoterin protein at the leading edges of BDV-infected cells. Moreover, the expression of the receptor for advanced glycation end products, of which the extracellular moiety is a receptor for amphoterin, was not significantly activated in BDV-infected cells during the process of extension, suggesting that the secretion of amphoterin from the cell surface is inhibited by the binding of the p24 protein. These results suggested that BDV infection may cause direct damage in the developing brain by inhibiting the function of amphoterin due to binding by the p24 phosphoprotein.Borna disease virus (BDV) is the prototype of a new family, Bornaviridae, within the nonsegmented negative-strand RNA viruses, the Mononegavirales (12, 45), which is characterized by low productivity, neurotropism, and nuclear localization for transcription and replication (8). Although BDV was originally described as an agent of nonpurulent encephalomyelitis in horses in Germany (40), BDV infection has now been found in a wide range of vertebrate species, including sheep, cattle, cats, and ostriches (6,28,40). Recent epidemiological studies have suggested that BDV infection also occurs in humans and that it may be related to certain psychiatric diseases (7,13,22,27,43). Human BDV was isolated from the peripheral blood granulocyte cell fraction of a psychiatric patient (35). Furthermore, we have also demonstrated BDV infection in the brain of a schizophrenic patient with a very recent onset of disease (32).BDV shows noncytolytic replication in cultured cells. However, neonatal rats infected with BDV develop persistent infection and show developmental disturbances affecting specific areas of the brain (4,9,14,19,42). Neonatal BDV infection also result...

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Section: Bdv P24 Phosphoprotein Binds a 30-kda Proteinmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Borna Disease Virus Phosphoprotein Binds a Neurite Outgrowth Factor, Amphoterin/HMG-1

Kamitani

Shoya

Kobayashi

et al. 2001

J Virol

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“…Recognition of the association of N and P (soluble antigen complex) dates from the earliest attempts to purify BDV proteins from infected cells and tissues (23)(24)(25). Although the presence of the soluble antigen continues to be a mainstay in BDV clinical diagnostics, the basis for complex formation and its significance in the virus life cycle remain poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Interactions of the Borna Disease Virus P, N, and X Proteins and Their Functional Implications

Schwemmle

Salvatore

Shi

et al. 1998

Journal of Biological Chemistry

107

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Borna disease virus (BDV) causes persistent central nervous system infection and behavioral disturbances in warm-blooded animals. Protein interaction studies were pursued to gain insight into the functions of the putative nucleoprotein (N), phosphoprotein (P), atypical glycoprotein (gp18), and X protein (X) of BDV. Coimmunoprecipitation experiments indicated that N and P, and P and X, form complexes in infected cells. Twohybrid analyses confirmed interactions between P and P, P and X, and P and N, but not between P and gp18, N and gp18, X and gp18, or X and N. Analysis of P truncation mutants identified three nonoverlapping regions important for oligomerization (amino acids (aa) 135-172), and binding to X (aa 33-115) or N (aa 197-201). Coexpression of X stimulated oligomerization of P but decreased N-P complex formation. Immunocytochemistry of transfected noninfected CHO cells demonstrated that the distribution of X is dependent upon the presence of P-X expressed alone was found predominantly in the cytoplasm whereas coexpression of X and P resulted in nuclear localization. Immunocytochemistry of infected cells revealed nuclear colocalization of P and X. Interactions of P, N, and X may have implications for regulation of BDV transcription/replication and ribonucleoprotein assembly. Borna disease virus (BDV)1 is a nonsegmented, negativestrand RNA virus that infects a broad range of warm-blooded animal species to cause disturbances of movement and behavior (1-5). The antigenome of BDV contains at least six major open reading frames (ORFs) corresponding to the nucleoprotein (N), phosphoprotein (P), atypical glycoprotein (gp18), type I membrane glycoprotein (G), polymerase, and X-protein (X). Both N and P are abundant in infected cells. N is translated from a monocistronic RNA representing the first transcription unit. P is translated from an RNA representing the second transcription unit that contains coding sequences for both P and X. gp18, G, and polymerase are translated from RNAs generated from the third transcription unit by alternative splicing of one or two introns and are present only at low levels in infected cells (6). BDV replicates in the nucleus of infected cells (7-9). Thus, transport of viral RNA and protein between nucleus and cytoplasm is an essential feature of its life cycle. Nuclear localization signals are proposed for the P (10), N (11), and polymerase proteins (12, 13). In infected cells and tissues, N colocalizes with P and was recently reported to colocalize with X (14).The phosphoproteins of nonsegmented, negative-strand RNA viruses are essential for virus transcription and replication (7). Their phosphorylation by cellular kinases influences the ability of phosphoproteins to form homomultimers, bind other viral proteins, and serve as transcriptional activators. Here, we characterize the interactions between X, P, and N in vitro and in vivo and define X as a positive regulator of P-P multimerization. EXPERIMENTAL PROCEDURESCell Lines-COS-7 and C6 cells were maintained in Dulbecco's modifie...

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“…In addition, a small ORF X, which overlaps p24 ORF, was recently reported to encode a novel protein X (p10) that has an unknown function [15,23]. Of these proteins, BDV-p40 and -p24 are found as abundant proteins in BDV-infected brain cells of experimentally and naturally infected animals [1]. Furthermore, experimental infection of BDV demonstrated that antibodies against BDVp40 and -p24 proteins were readily detected in both sera and cerebrospinal fluid of infected hosts [8].…”

mentioning

confidence: 99%

“…The ORFs encode nucleoprotein (p40), phosphoprotein (p24), matrix protein (gp18), envelope protein (p56), and a predicted RNA-dependent RNA polymerase (p180) in 5' to 3' order [1,5,11,21]. In addition, a small ORF X, which overlaps p24 ORF, was recently reported to encode a novel protein X (p10) that has an unknown function [15,23].…”

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confidence: 99%

Antibodies to Borna Disease Virus in Infected Adult Rats: An Early Appearance of Anti-p10 Antibody and Recognition of Novel Virus-Specific Proteins in Infected Animal Brain Cells.

Watanabe

Kobayashi

Tomonaga

et al. 2000

The Journal of Veterinary Medical Science

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ABSTRACT. The time course for appearance of antibodies to Borna disease virus (BDV) major antigens, p40, p24, p18 and p10 were investigated in BDV-inoculated adult rats by Western blotting. Anti-p10 antibodies were detected in sera as early as anti-p40 and -p24 antibodies at four or five weeks after inoculation. Furthermore, in addition to these major antigens of BDV, the rat serum could detect additional 80-, 58-, 43-, 20-, and 16-kDa proteins in BDV-infected cultured cells and/or animal brain cells by Western blot analysis. Of these proteins, the 20-and 16-kDa proteins were shown to be related to p24 protein by their reactivity with anti-p24 monoclonal antibody. Interestingly, the 58-and 24-kDa were found only in BDV-infected animal brain cells but not in cultured cells. The results in this study could provide a useful information on the mechanism for the viral replication and pathogenesis.KEY WORDS: animal brain, antibody, Borna disease virus.

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Borna disease virus-specific antigens: two different proteins identified by monoclonal antibodies

Cited by 23 publications

References 16 publications

Borna Disease Virus Phosphoprotein Binds a Neurite Outgrowth Factor, Amphoterin/HMG-1

Borna Disease Virus Phosphoprotein Binds a Neurite Outgrowth Factor, Amphoterin/HMG-1

Interactions of the Borna Disease Virus P, N, and X Proteins and Their Functional Implications

Antibodies to Borna Disease Virus in Infected Adult Rats: An Early Appearance of Anti-p10 Antibody and Recognition of Novel Virus-Specific Proteins in Infected Animal Brain Cells.

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