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  1. Article ; Online: Linkage between the leader sequence and leader RNA production in Borna disease virus-infected cells.

    Honda, Tomoyuki / Sofuku, Kozue / Kojima, Shohei / Yamamoto, Yusuke / Ohtaki, Naohiro / Tomonaga, Keizo

    Virology

    2017  Volume 510, Page(s) 104–110

    Abstract: The 3'-untranslated region (UTR) of the non-segmented, negative-strand (NNS) RNA viral genome is called the leader sequence, and functions as the promoter for viral replication and transcription. NNS RNA viruses also use the sequence as a template to ... ...

    Abstract The 3'-untranslated region (UTR) of the non-segmented, negative-strand (NNS) RNA viral genome is called the leader sequence, and functions as the promoter for viral replication and transcription. NNS RNA viruses also use the sequence as a template to synthesize leader RNAs (leRNAs) with unknown functions. Borna disease virus (BDV) is unique because it establishes a persistent infection and replicates in the nucleus. No report has yet demonstrated the presence of leRNAs during BDV infection. Here, we report that BDV synthesizes leRNAs from the 3'-UTR of the genome. They started at position 5 in the 3'-UTR and ended by the transcription start signal of the nucleoprotein gene. The level of leRNA production is not correlated with the levels of viral replication and transcription. On the other hand, mutation of the 3'-UTR affects leRNA production. Our findings add a novel viral transcript to the BDV life cycle and shed light on BDV replication and/or transcription.
    MeSH term(s) 3' Untranslated Regions ; Borna disease virus/genetics ; Gene Expression Profiling ; RNA, Viral/biosynthesis ; Transcription, Genetic
    Chemical Substances 3' Untranslated Regions ; RNA, Viral
    Language English
    Publishing date 2017-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2017.07.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.

    Watanabe, Yohei / Ohtaki, Naohiro / Hayashi, Yohei / Ikuta, Kazuyoshi / Tomonaga, Keizo

    PLoS pathogens

    2009  Volume 5, Issue 11, Page(s) e1000654

    Abstract: Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression. The shortest transcript of BDV, X/P mRNA, encodes at least three open reading frames (ORFs): upstream ORF (uORF), X, and P ... ...

    Abstract Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression. The shortest transcript of BDV, X/P mRNA, encodes at least three open reading frames (ORFs): upstream ORF (uORF), X, and P in the 5' to 3' direction. The X is a negative regulator of viral polymerase activity, while the P phosphoprotein is a necessary cofactor of the polymerase complex, suggesting that the translation of X is controlled rigorously, depending on viral replication. However, the translation mechanism used by the X/P polycistronic mRNA has not been determined in detail. Here we demonstrate that the X/P mRNA autogenously regulates the translation of X via interaction with host factors. Transient transfection of cDNA clones corresponding to the X/P mRNA revealed that the X ORF is translated predominantly by uORF-termination-coupled reinitiation, the efficiency of which is upregulated by expression of P. We found that P may enhance ribosomal reinitiation at the X ORF by inhibition of the interaction of the DEAD-box RNA helicase DDX21 with the 5' untranslated region of X/P mRNA, via interference with its phosphorylation. Our results not only demonstrate a unique translational control of viral regulatory protein, but also elucidate a previously unknown mechanism of regulation of polycistronic mRNA translation using RNA helicases.
    MeSH term(s) Borna disease virus/genetics ; Gene Expression Regulation, Viral ; Host-Pathogen Interactions ; RNA Helicases/metabolism ; RNA, Viral/metabolism ; Viral Regulatory and Accessory Proteins/genetics
    Chemical Substances RNA, Viral ; Viral Regulatory and Accessory Proteins ; RNA Helicases (EC 3.6.4.13)
    Language English
    Publishing date 2009-11-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1000654
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Autogenous translational regulation of the Borna disease virus negative control factor X from polycistronic mRNA using host RNA helicases.

    Yohei Watanabe / Naohiro Ohtaki / Yohei Hayashi / Kazuyoshi Ikuta / Keizo Tomonaga

    PLoS Pathogens, Vol 5, Iss 11, p e

    2009  Volume 1000654

    Abstract: Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression. The shortest transcript of BDV, X/P mRNA, encodes at least three open reading frames (ORFs): upstream ORF (uORF), X, and P ... ...

    Abstract Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that employs several unique strategies for gene expression. The shortest transcript of BDV, X/P mRNA, encodes at least three open reading frames (ORFs): upstream ORF (uORF), X, and P in the 5' to 3' direction. The X is a negative regulator of viral polymerase activity, while the P phosphoprotein is a necessary cofactor of the polymerase complex, suggesting that the translation of X is controlled rigorously, depending on viral replication. However, the translation mechanism used by the X/P polycistronic mRNA has not been determined in detail. Here we demonstrate that the X/P mRNA autogenously regulates the translation of X via interaction with host factors. Transient transfection of cDNA clones corresponding to the X/P mRNA revealed that the X ORF is translated predominantly by uORF-termination-coupled reinitiation, the efficiency of which is upregulated by expression of P. We found that P may enhance ribosomal reinitiation at the X ORF by inhibition of the interaction of the DEAD-box RNA helicase DDX21 with the 5' untranslated region of X/P mRNA, via interference with its phosphorylation. Our results not only demonstrate a unique translational control of viral regulatory protein, but also elucidate a previously unknown mechanism of regulation of polycistronic mRNA translation using RNA helicases.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2009-11-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Prevalence of Borna disease virus antibodies in healthy Japanese black cattle in Kyushu.

    Watanabe, Yohei / Yanai, Hideyuki / Ohtaki, Naohiro / Ikuta, Kazuyoshi / Tomonaga, Keizo

    The Journal of veterinary medical science

    2006  Volume 68, Issue 2, Page(s) 171–174

    Abstract: Epidemiological studies have demonstrated that asymptomatic infection of Borna disease virus (BDV) is found in various species of animals in Japan. Recent reports have also revealed that neurological diseases caused by this virus could exist in horses, ... ...

    Abstract Epidemiological studies have demonstrated that asymptomatic infection of Borna disease virus (BDV) is found in various species of animals in Japan. Recent reports have also revealed that neurological diseases caused by this virus could exist in horses, cattle, a dog, and cats in this country. In this study, we investigated seroprevalence of BDV antibodies in Japanese black cows reared in Kyushu, the southernmost main island of Japan, using ELISA and Western-immunoblotting. Of 101 serum samples, 11 (10.9%) and 21(20.7%) sera were identified as having antibodies to the BDV N and P antigens, respectively. Among the positive sera, three cows (2.9%) were seropositive for both of the antigens. Furthermore, interestingly, only female cows showed antibodies to P, whereas N antibodies were detected in male and female cows with a comparative ratio. Together with previous studies, our results indicate that BDV might be widely spread in cattle raised in Japan. Furthermore, this is the first report to show that beef cattle, Japanese black cattle, have antibodies against a possible zoonotic pathogen, BDV.
    MeSH term(s) Animals ; Antibodies, Viral/blood ; Blotting, Western/veterinary ; Borna Disease/epidemiology ; Borna Disease/virology ; Borna disease virus/isolation & purification ; Cattle ; Cattle Diseases/epidemiology ; Cattle Diseases/virology ; Enzyme-Linked Immunosorbent Assay/veterinary ; Female ; Japan/epidemiology ; Male ; Nervous System Diseases/epidemiology ; Nervous System Diseases/veterinary ; Nervous System Diseases/virology ; Nucleocapsid Proteins ; Seroepidemiologic Studies
    Chemical Substances Antibodies, Viral ; Nucleocapsid Proteins
    Language English
    Publishing date 2006-03-05
    Publishing country Japan
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071753-5
    ISSN 1347-7439 ; 0916-7250
    ISSN (online) 1347-7439
    ISSN 0916-7250
    DOI 10.1292/jvms.68.171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Upregulation of insulin-like growth factor binding protein 3 in astrocytes of transgenic mice that express Borna disease virus phosphoprotein.

    Honda, Tomoyuki / Fujino, Kan / Okuzaki, Daisuke / Ohtaki, Naohiro / Matsumoto, Yusuke / Horie, Masayuki / Daito, Takuji / Itoh, Masayuki / Tomonaga, Keizo

    Journal of virology

    2011  Volume 85, Issue 9, Page(s) 4567–4571

    Abstract: In a previous study, we demonstrated that transgenic mice that express Borna disease virus (BDV) phosphoprotein (P) in astrocytes show striking neurobehavioral abnormalities resembling those in BDV-infected animals. To understand the molecular ... ...

    Abstract In a previous study, we demonstrated that transgenic mice that express Borna disease virus (BDV) phosphoprotein (P) in astrocytes show striking neurobehavioral abnormalities resembling those in BDV-infected animals. To understand the molecular disturbances induced by the expression of P in astrocytes, we performed microarray analysis with cultured astroglial cells transiently expressing P. We showed that expression of insulin-like growth factor binding protein 3 mRNA increases not only in P-expressing cultured cells but also in astrocytes from the cerebella of P transgenic mice (P-Tg). Furthermore, we demonstrated that insulin-like growth factor signaling is disturbed in the P-Tg cerebellum, a factor that might be involved in the increased vulnerability of Purkinje cell neurons in the brain.
    MeSH term(s) Animals ; Astrocytes/virology ; Borna disease virus/pathogenicity ; Cells, Cultured ; Gene Expression Profiling ; Insulin-Like Growth Factor Binding Protein 3/biosynthesis ; Mice ; Mice, Transgenic ; Microarray Analysis ; Phosphoproteins/metabolism ; Up-Regulation ; Viral Structural Proteins/metabolism
    Chemical Substances Insulin-Like Growth Factor Binding Protein 3 ; P protein, Borna disease virus ; Phosphoproteins ; Viral Structural Proteins
    Language English
    Publishing date 2011-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.01817-10
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Purification and concentration of non-infectious West Nile virus-like particles and infectious virions using a pseudo-affinity Cellufine Sulfate column.

    Ohtaki, Naohiro / Takahashi, Hidehiro / Kaneko, Keiko / Gomi, Yasuyuki / Ishikawa, Toyokazu / Higashi, Yasushi / Todokoro, Masami / Kurata, Takeshi / Sata, Tetsutaro / Kojima, Asato

    Journal of virological methods

    2011  Volume 174, Issue 1-2, Page(s) 131–135

    Abstract: Affinity column chromatography is a promising method for the purification of flavivirus particles that can supplement or potentially replace diafiltration and sucrose density centrifugation. In this study, the purification of West Nile Virus (WNV) ... ...

    Abstract Affinity column chromatography is a promising method for the purification of flavivirus particles that can supplement or potentially replace diafiltration and sucrose density centrifugation. In this study, the purification of West Nile Virus (WNV) antigens via Cellufine Sulfate column chromatography was examined. Virus-like particles (VLPs) produced by the expression of the prM and E genes were separated from most of the contaminant proteins with 0.2-0.4M NaCl, but still retained their spherical forms and immunogenicity in mice. The column, with a 1 mL bed-volume, concentrated WN-VLPs a minimum of 15 fold from culture supernatants. A heparin analogue, suramin, competitively eluted WN-VLPs, but sulphated polysaccharides, such as heparin, heparin sulfate and dextran sulfate, did not. Furthermore, 2.4 × 10⁹ plaque forming units of WNV and 196 μg of the viral antigens were recovered from 60 mL of infected culture medium at high yields (93% and 96%, respectively). These results indicate that, in addition to conventional methods, Cellufine Sulfate column chromatography is an effective preparation technique for WNV particulate antigens that does not impair the antigen virological characteristics.
    MeSH term(s) Animals ; Chromatography, Affinity/methods ; Chromatography, Liquid/methods ; Mice ; Virion/isolation & purification ; Virology/methods ; Virosomes/isolation & purification ; West Nile virus/isolation & purification
    Chemical Substances Virosomes
    Language English
    Publishing date 2011-06
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2011.03.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate.

    Ohtaki, Naohiro / Takahashi, Hidehiro / Kaneko, Keiko / Gomi, Yasuyuki / Ishikawa, Toyokazu / Higashi, Yasushi / Kurata, Takeshi / Sata, Tetsutaro / Kojima, Asato

    Vaccine

    2010  Volume 28, Issue 40, Page(s) 6588–6596

    Abstract: Virus-like particles (VLPs) of flaviviruses generated from the prM and E genes are a promising vaccine candidate. We have established cell clones continuously releasing VLPs of West Nile virus (WNV) in serum-free conditions. Two types of VLPs were ... ...

    Abstract Virus-like particles (VLPs) of flaviviruses generated from the prM and E genes are a promising vaccine candidate. We have established cell clones continuously releasing VLPs of West Nile virus (WNV) in serum-free conditions. Two types of VLPs were distinguished by sedimenting analyses in sucrose density gradients. Fast sedimenting VLPs (F-VLPs) were large (40-50 nm) and composed of the E and processed mature M proteins, whereas slowly sedimenting VLPs (S-VLPs) were small (20-30 nm) particles consisting of the E and immature prM proteins. F-VLPs induced higher neutralizing antibody and anti-WNV IgG titers than S-VLPs. Furthermore, IgG2a was dominant over IgG1 by immunization with F-VLPs as with whole virion-derived antigens. Mice vaccinated with a low dose (3 ng) of F-VLPs showed higher protective efficacy (83% survivals) against WNV infection than S-VLP-immune mice (17% survivals). These results indicate that F-VLPs more closely resemble the virions and take a better immunogenic form than S-VLPs as WNV vaccine candidates.
    MeSH term(s) Animals ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Antibody Formation ; CHO Cells ; Centrifugation, Density Gradient ; Cricetinae ; Cricetulus ; Immunoglobulin G/blood ; Mice ; Mice, Inbred C3H ; Particle Size ; Vaccines, Virus-Like Particle/immunology ; Viral Envelope Proteins/immunology ; Viral Matrix Proteins/immunology ; West Nile Fever/immunology ; West Nile Fever/prevention & control ; West Nile Virus Vaccines/immunology ; West Nile virus/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin G ; Vaccines, Virus-Like Particle ; Viral Envelope Proteins ; Viral Matrix Proteins ; West Nile Virus Vaccines
    Language English
    Publishing date 2010-09-14
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2010.07.055
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Downregulation of an astrocyte-derived inflammatory protein, S100B, reduces vascular inflammatory responses in brains persistently infected with Borna disease virus.

    Ohtaki, Naohiro / Kamitani, Wataru / Watanabe, Yohei / Hayashi, Yohei / Yanai, Hideyuki / Ikuta, Kazuyoshi / Tomonaga, Keizo

    Journal of virology

    2007  Volume 81, Issue 11, Page(s) 5940–5948

    Abstract: Borna 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 ... ...

    Abstract Borna 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 Ca(2+)-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.
    MeSH term(s) Animals ; Astrocytes/metabolism ; Astrocytes/pathology ; Borna Disease/metabolism ; Borna Disease/pathology ; Borna Disease/physiopathology ; Borna disease virus/physiology ; Brain/blood supply ; Brain/pathology ; Brain/virology ; Chronic Disease ; Down-Regulation/physiology ; Nerve Growth Factors/antagonists & inhibitors ; Nerve Growth Factors/biosynthesis ; Rats ; Rats, Inbred Lew ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins/antagonists & inhibitors ; S100 Proteins/biosynthesis ; Vasculitis, Central Nervous System/pathology ; Vasculitis, Central Nervous System/physiopathology ; Vasculitis, Central Nervous System/virology
    Chemical Substances Nerve Growth Factors ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; S100b protein, rat
    Language English
    Publishing date 2007-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.02137-06
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Development of a novel Borna disease virus reverse genetics system using RNA polymerase II promoter and SV40 nuclear import signal.

    Yanai, Hideyuki / Hayashi, Yohei / Watanabe, Yohei / Ohtaki, Naohiro / Kobayashi, Takeshi / Nozaki, Yasutoshi / Ikuta, Kazuyoshi / Tomonaga, Keizo

    Microbes and infection

    2006  Volume 8, Issue 6, Page(s) 1522–1529

    Abstract: Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that replicates and transcribes in the nucleus of infected cells. Therefore, efficient synthesis of BDV RNA in the nucleus is critical for the development of a reverse genetics system for ...

    Abstract Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that replicates and transcribes in the nucleus of infected cells. Therefore, efficient synthesis of BDV RNA in the nucleus is critical for the development of a reverse genetics system for this virus. Here, we report the development of such a system using the RNA polymerase II (Pol II) promoter. The BDV minigenome cDNA was flanked by hammerhead ribozyme and hepatitis delta ribozyme sequences and inserted downstream of the Pol II promoter. To improve the efficacy of minigenome expression, we estimated the effects of several signal sequences within the minigenome constructs. We found that insertion of the SV40 nuclear import sequence into the Pol II constructs significantly enhances the replication of the minigenome even in cells lacking the SV40 large T antigen. This novel system is theoretically applicable to any mammalian cell line and would be valuable for analyzing host- or cell-type-dependent differences in BDV replication and production. We could demonstrate here the cell-type-dependent inhibitory effect of the viral protein X on BDV polymerase activity. This system may be useful for various research fields not only of BDV but also of other negative-sense RNA viruses.
    MeSH term(s) Active Transport, Cell Nucleus/genetics ; Animals ; Base Sequence ; Borna disease virus/genetics ; Cell Line, Tumor ; Cercopithecus aethiops ; Cricetinae ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique, Indirect ; Humans ; Molecular Sequence Data ; Nucleic Acid Conformation ; Oligopeptides/genetics ; Plasmids/genetics ; Promoter Regions, Genetic ; RNA Polymerase II/genetics ; RNA, Catalytic/genetics ; Transfection ; Vero Cells
    Chemical Substances Oligopeptides ; RNA, Catalytic ; SV40 nuclear localization peptide ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2006-05
    Publishing country France
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1465093-9
    ISSN 1769-714X ; 1286-4579
    ISSN (online) 1769-714X
    ISSN 1286-4579
    DOI 10.1016/j.micinf.2006.01.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Persistent borna disease virus infection confers instability of HSP70 mRNA in glial cells during heat stress.

    Yamashita, Makiko / Kamitani, Wataru / Yanai, Hideyuki / Ohtaki, Naohiro / Watanabe, Yohei / Lee, Byeong-Jae / Tsuji, Shoutaro / Ikuta, Kazuyoshi / Tomonaga, Keizo

    Journal of virology

    2005  Volume 79, Issue 4, Page(s) 2033–2041

    Abstract: Borna disease virus (BDV) is a highly neurotropic RNA virus that causes neurological disorders in many vertebrate species. Although BDV readily establishes lasting persistence, persistently infected cells maintain an apparently normal cell phenotype in ... ...

    Abstract Borna disease virus (BDV) is a highly neurotropic RNA virus that causes neurological disorders in many vertebrate species. Although BDV readily establishes lasting persistence, persistently infected cells maintain an apparently normal cell phenotype in terms of morphology, viability, and proliferation. In this study, to understand the regulation of stress responses in BDV infection, we investigated the expression of heat shock proteins (HSPs) in glial cells persistently infected with BDV. Interestingly, we found that BDV persistence did not upregulate HSP70 expression even in cells treated with heat stress. Furthermore, BDV-infected glial cells exhibited rapid rounding and detachment from the culture plate under various stressful conditions. Immunofluorescence analysis demonstrated that heat stress rapidly disrupts the cell cytoskeleton only in persistently infected cells, suggesting a lack of thermotolerance. Intriguingly, we found that although persistently infected glial cells expressed HSP70 mRNA after heat stress, its expression rapidly disappeared during the recovery period. These observations indicated that persistent BDV infection may affect the stability of HSP70 mRNA. Finally, we found that the double-stranded RNA-dependent protein kinase (PKR) is expressed at a constant level in persistently infected cells with or without heat shock. Considering the interrelationship between HSP70 and PKR production, our data suggest that BDV infection disturbs the cellular stress responses to abolish antiviral activities and maintain persistence.
    MeSH term(s) Animals ; Borna Disease/metabolism ; Borna Disease/pathology ; Borna disease virus ; Cell Line ; Gene Expression Regulation, Viral ; HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/metabolism ; Hot Temperature ; Neuroglia/cytology ; Neuroglia/virology ; Protein Kinases/metabolism ; RNA, Double-Stranded/metabolism ; RNA, Messenger/metabolism ; Rats ; Stress, Physiological/metabolism ; Temperature ; Transcription, Genetic
    Chemical Substances HSP70 Heat-Shock Proteins ; RNA, Double-Stranded ; RNA, Messenger ; Protein Kinases (EC 2.7.-)
    Language English
    Publishing date 2005-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.79.4.2033-2041.2005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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