Base de dados : MEDLINE
Pesquisa : C02.782.580.124 [Categoria DeCS]
Referências encontradas : 560 [refinar]
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[PMID]:28465146
[Au] Autor:Tokunaga T; Yamamoto Y; Sakai M; Tomonaga K; Honda T
[Ad] Endereço:Laboratory of RNA Viruses, Department of Virus Research, Institute for Frontier Life and Medical Sciences (InFRONT), Kyoto University, Kyoto, Japan; Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
[Ti] Título:Antiviral activity of favipiravir (T-705) against mammalian and avian bornaviruses.
[So] Source:Antiviral Res;143:237-245, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bornaviruses, non-segmented, negative-strand RNA viruses, are emerging agents with the potential for causing various types of neurological symptoms. Previous studies have shown that ribavirin, a nucleic acid analog with broad-spectrum antiviral activity, has a potent antiviral effect on infections with a mammalian bornavirus, Borna disease virus (BoDV-1), as well as avian bornaviruses. However, ribavirin-based treatment does not eliminate bornaviruses from persistently infected cells and viral replication resumes after treatment cessation. Therefore, the development of a novel effective anti-bornavirus treatment is needed. To identify such agents, we screened nucleoside/nucleotide mimetics for agents with anti-bornavirus activity. We used Vero cells infected with recombinant BoDV-1 carrying Gaussia luciferase to monitor BoDV-1 replication and found that favipiravir (T-705) is a potent inhibitor of BoDV-1 replication. T-705 suppressed BoDV-1 replication in a dose- and time-dependent manner during the observation period of 4 weeks. Notably, no increase in luciferase activity or in the number of BoDV-1-positive cells was detected in the at least 4 weeks following T-705 removal. Finally, we demonstrated that T-705 effectively suppressed viral replication of both BoDV-1 and an avian bornavirus, suggesting that T-705 may have a strong antiviral activity against a broad range of bornaviruses. Our findings provide a novel and effective option for treating persistent bornavirus infection.
[Mh] Termos MeSH primário: Amidas/farmacologia
Antivirais/farmacologia
Bornaviridae/efeitos dos fármacos
Pirazinas/farmacologia
[Mh] Termos MeSH secundário: Amidas/administração & dosagem
Animais
Antivirais/administração & dosagem
Doenças das Aves/virologia
Doença de Borna/tratamento farmacológico
Doença de Borna/virologia
Vírus da Doença de Borna/genética
Bornaviridae/genética
Linhagem Celular
Cercopithecus aethiops
Testes de Sensibilidade Microbiana
Pirazinas/administração & dosagem
Codorniz
RNA Viral/análise
Fatores de Tempo
Células Vero
Carga Viral/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amides); 0 (Antiviral Agents); 0 (Pyrazines); 0 (RNA, Viral); EW5GL2X7E0 (favipiravir)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:28446679
[Au] Autor:Formisano S; Hornig M; Yaddanapudi K; Vasishtha M; Parsons LH; Briese T; Lipkin WI; Williams BL
[Ad] Endereço:Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.
[Ti] Título:Central Nervous System Infection with Borna Disease Virus Causes Kynurenine Pathway Dysregulation and Neurotoxic Quinolinic Acid Production.
[So] Source:J Virol;91(14), 2017 Jul 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Central nervous system infection of neonatal and adult rats with Borna disease virus (BDV) results in neuronal destruction and behavioral abnormalities with differential immune-mediated involvement. Neuroactive metabolites generated from the kynurenine pathway of tryptophan degradation have been implicated in several human neurodegenerative disorders. Here, we report that brain expression of key enzymes in the kynurenine pathway are significantly, but differentially, altered in neonatal and adult rats with BDV infection. Gene expression analysis of rat brains following neonatal infection showed increased expression of kynurenine amino transferase II (KATII) and kynurenine-3-monooxygenase (KMO) enzymes. Additionally, indoleamine 2,3-dioxygenase (IDO) expression was only modestly increased in a brain region- and time-dependent manner in neonatally infected rats; however, its expression was highly increased in adult infected rats. The most dramatic impact on gene expression was seen for KMO, whose activity promotes the production of neurotoxic quinolinic acid. KMO expression was persistently elevated in brain regions of both newborn and adult BDV-infected rats, with increases reaching up to 86-fold. KMO protein levels were increased in neonatally infected rats and colocalized with neurons, the primary target cells of BDV infection. Furthermore, quinolinic acid was elevated in neonatally infected rat brains. We further demonstrate increased expression of KATII and KMO, but not IDO, in BDV-infected C6 astroglioma cells. Our results suggest that BDV directly impacts the kynurenine pathway, an effect that may be exacerbated by inflammatory responses in immunocompetent hosts. Thus, experimental models of BDV infection may provide new tools for discriminating virus-mediated from immune-mediated impacts on the kynurenine pathway and their relative contribution to neurodegeneration. BDV causes persistent, noncytopathic infection yet still elicits widespread neurodegeneration of infected neurons in both immunoincompetent and immunocompetent hosts. Here, we show that BDV infection induces expression of key enzymes of the kynurenine pathway in brains of newborn and adult infected rats and cultured astroglioma cells, shunting tryptophan degradation toward the production of neurotoxic quinolinic acid. Thus, our findings newly implicate this metabolic pathway in BDV-induced neurodegeneration. Given the importance of the kynurenine pathway in a wide range of human infections and neurodegenerative and neuropsychiatric disorders, animal models of BDV infection may serve as important tools for contrasting direct viral and indirect antiviral immune-mediated impacts on kynurenine pathway dysregulation and the ensuing neurodevelopmental and neuropathological consequences.
[Mh] Termos MeSH primário: Doença de Borna/fisiopatologia
Vírus da Doença de Borna/crescimento & desenvolvimento
Encéfalo/patologia
Interações Hospedeiro-Patógeno
Cinurenina/metabolismo
Redes e Vias Metabólicas
Ácido Quinolínico/toxicidade
[Mh] Termos MeSH secundário: Animais
Doença de Borna/patologia
Linhagem Celular
Modelos Animais de Doenças
Perfilação da Expressão Gênica
Regulação da Expressão Gênica
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
343-65-7 (Kynurenine); F6F0HK1URN (Quinolinic Acid)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


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[PMID]:27902378
[Au] Autor:Charlier CM; Debaisieux S; Foret C; Thouard A; Schiavo G; Gonzalez-Dunia D; Malnou CE
[Ad] Endereço:1​Centre de Physiopathologie de Toulouse Purpan, INSERM UMR 1043, CNRS UMR 5282, Université Toulouse III Paul Sabatier, Toulouse, France.
[Ti] Título:Neuronal retrograde transport of Borna disease virus occurs in signalling endosomes.
[So] Source:J Gen Virol;97(12):3215-3224, 2016 Dec.
[Is] ISSN:1465-2099
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Long-range axonal retrograde transport is a key mechanism for the cellular dissemination of neuroinvasive viruses, such as Borna disease virus (BDV), for which entry and egress sites are usually distant from the nucleus, where viral replication takes place. Although BDV is known to disseminate very efficiently in neurons, both in vivo and in primary cultures, the modalities of its axonal transport are still poorly characterized. In this work, we combined different methodological approaches, such as confocal microscopy and biochemical purification of endosomes, to study BDV retrograde transport. We demonstrate that BDV ribonucleoparticles (composed of the viral genomic RNA, nucleoprotein and phosphoprotein), as well as the matrix protein, are transported towards the nucleus into endocytic carriers. These specialized organelles, called signalling endosomes, are notably used for the retrograde transport of neurotrophins and activated growth factor receptors. Signalling endosomes have a neutral luminal pH and thereby offer protection against degradation during long-range transport. This particularity could allow the viral particles to be delivered intact to the cell body of neurons, avoiding their premature release in the cytoplasm.
[Mh] Termos MeSH primário: Doença de Borna/virologia
Vírus da Doença de Borna/metabolismo
Endossomos/virologia
Neurônios/virologia
[Mh] Termos MeSH secundário: Animais
Doença de Borna/metabolismo
Vírus da Doença de Borna/genética
Núcleo Celular/metabolismo
Núcleo Celular/virologia
Endossomos/metabolismo
Neurônios/metabolismo
Fosfoproteínas/genética
Fosfoproteínas/metabolismo
RNA Viral/genética
RNA Viral/metabolismo
Ratos
Ratos Sprague-Dawley
Proteínas Virais/genética
Proteínas Virais/metabolismo
Vírion/genética
Vírion/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphoproteins); 0 (RNA, Viral); 0 (Viral Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170512
[Lr] Data última revisão:
170512
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161201
[St] Status:MEDLINE
[do] DOI:10.1099/jgv.0.000652


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[PMID]:27878262
[Au] Autor:Mao Q; Zhang L; Guo Y; Sun L; Liu S; He P; Huang R; Sun L; Chen S; Zhang H; Xie P
[Ad] Endereço:Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, P.R. China.
[Ti] Título:Identification of suitable reference genes for BDV-infected primary rat hippocampal neurons.
[So] Source:Mol Med Rep;14(6):5587-5594, 2016 Dec.
[Is] ISSN:1791-3004
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Borna disease virus (BDV) is a neurotropic RNA virus that infects the limbic system of mammals and results in behavioral disorders. The hippocampus is a core region in the limbic system, which contributes to memory and learning and is important in the regulation of emotion. However, no validated microRNA housekeeping genes have yet been identified in BDV­infected rat primary hippocampal neurons. Proper normalization is key in accurate miRNA expression analysis. The present study used reverse transcription­quantitative polymerase chain reaction (RT­qPCR) to evaluate the expression stability of 10 commonly used reference genes [miR­92a, 5S, U6, miR­103, miR­101a, miR-let-7a, miR­16, E2 small nucleolar RNA (snoRNA), U87 and miR­191] in BDV­infected rat hippocampal neurons and non­infected controls across 12 days post­infection. The data was analyzed by four statistical algorithms: geNorm, NormFinder, BestKeeper, and the comparative Δ­Ct method. Subsequently, the most suitable reference genes (miR­101a and U87) and the least suitable (snoRNA) were determined by the RankAggreg package. miR­155 was selected as a standard by which to evaluate the most and least suitable reference genes. When normalized to the most stable reference gene there were significant differences between the two groups. However, when the data were normalized to the less stably expressed gene, the results were not significant. miR­101a was recommended as a suitable reference gene for BDV-infected rat primary hippocampal neurons.
[Mh] Termos MeSH primário: Vírus da Doença de Borna/fisiologia
Regulação da Expressão Gênica
Células Piramidais/metabolismo
Células Piramidais/virologia
[Mh] Termos MeSH secundário: Animais
Doença de Borna/genética
Doença de Borna/virologia
Perfilação da Expressão Gênica
Imuno-Histoquímica
Masculino
MicroRNAs/genética
Estabilidade de RNA
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170406
[Lr] Data última revisão:
170406
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161124
[St] Status:MEDLINE
[do] DOI:10.3892/mmr.2016.5959


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[PMID]:27842550
[Au] Autor:Takino T; Okamura T; Ando T; Hagiwara K
[Ad] Endereço:School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.
[Ti] Título:Change in the responsiveness of interferon-stimulated genes during early pregnancy in cows with Borna virus-1 infection.
[So] Source:BMC Vet Res;12(1):253, 2016 Nov 14.
[Is] ISSN:1746-6148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Borna disease virus is a neurotropic pathogen and infects the central nervous system. This virus infected a variety of animal species including cows. The most of cows infected with Borna disease virus 1 (BoDV-1) exhibit subclinical infection without any neurological symptoms throughout their lifetime. We previously reported on the low conception rates in-seropositive cows. Interferon-τ (IFN-τ) plays an important role in stable fertilization, and is produced from the fetal side following embryo growth at 15-40 days of pregnancy. IFN-τ induces the expression of interferon-stimulated gene (ISG) 15 and Mx2 in peripheral blood mononuclear cells (PBMCs). To understand the embryo growth and maternal reaction during early pregnancy in cows with BoDV-1 infection, we aimed to assess the gene expression of ISG15 and Mx2 from PBMCs in BoDV-1-seropositive cows. RESULTS: None of the cows showed any clinical and neurological symptoms. Among the cows that conceived, the expressions of the ISG15 and Mx2 genes were greater in the BoDV-1-seropositive cows than in the BoDV-1-seronegative cows; the difference was significant between the cows that conceived and those that did not (P < 0.05). CONCLUSIONS: The expression of ISG15 and Mx2 genes during early pregnancy significantly increased in the BoDV-1-seropositive cows and may be important for the maintenance of stable pregnancy in BoDV-1-infected cows. In contrast, the gene expression levels of ISG15 and Mx2 did not significantly increase during early pregnancy in BoDV-1-seronegative cows. Thus, BoDV-1 infection may lead to instability in the maintenance of early pregnancy by interfering with INF-τ production.
[Mh] Termos MeSH primário: Doença de Borna/genética
Doença de Borna/imunologia
Doenças dos Bovinos/genética
Doenças dos Bovinos/imunologia
Citocinas/genética
Regulação da Expressão Gênica/imunologia
Proteínas de Resistência a Myxovirus/genética
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Vírus da Doença de Borna/fisiologia
Bovinos
Feminino
Interferons/metabolismo
Leucócitos Mononucleares/metabolismo
Gravidez
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Cytokines); 0 (Myxovirus Resistance Proteins); 9008-11-1 (Interferons)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161116
[St] Status:MEDLINE


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[PMID]:27809822
[Au] Autor:Zaliunaite V; Steibliene V; Bode L; Podlipskyte A; Bunevicius R; Ludwig H
[Ad] Endereço:Behavioral Medicine Institute, Lithuanian University of Health Sciences, Vyduno str. 4, Palanga, LT-00135, Lithuania. violeta.zaliunaite@lsmuni.lt.
[Ti] Título:Primary psychosis and Borna disease virus infection in Lithuania: a case control study.
[So] Source:BMC Psychiatry;16(1):369, 2016 Nov 03.
[Is] ISSN:1471-244X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The hypothesis that microbial infections may be linked to mental disorders has long been addressed for Borna disease virus (BDV), but clinical and epidemiological evidence remained inconsistent due to non-conformities in detection methods. BDV circulating immune complexes (CIC) were shown to exceed the prevalence of serum antibodies alone and to comparably screen for infection in Europe (DE, CZ, IT), the Middle East (IR) and Asia (CN), still seeking general acceptance. METHODS: We used CIC and antigen (Ag) tests to investigate BDV infection in Lithuania through a case-control study design comparing in-patients suffering of primary psychosis with blood donors. One hundred and six acutely psychotic in-patients with no physical illness, consecutively admitted to the regional mental hospital, and 98 blood donors from the Blood Donation Centre, Lithuania, were enrolled in the study. The severity of psychosis was assessed twice, prior and after acute antipsychotic therapy, by the Brief Psychiatric Rating Scale (BPRS). BDV-CIC and Ag markers were tested once after therapy was terminated. RESULTS: What we found was a significantly higher prevalence of CIC, indicating a chronic BDV infection, in patients with treated primary psychosis than in blood donor controls (39.6 % vs. 22.4 %, respectively). Free BDV Ag, indicating currently active infection, did not show significant differences among study groups. Higher severity of psychosis prior to treatment was inversely correlated to the presence of BDV Ag (42.6 vs. 34.1 BPRS, respectively; p = 0.022). CONCLUSIONS: The study concluded significantly higher BDV infection rates in psychotic than in healthy Lithuanians, thus supporting similar global trends for other mental disorders. The study raised awareness to consider the integration of BDV infection surveillance in psychiatry research in the future.
[Mh] Termos MeSH primário: Doença de Borna/epidemiologia
Doença de Borna/psicologia
Vírus da Doença de Borna
Transtornos Psicóticos/virologia
[Mh] Termos MeSH secundário: Animais
Doença de Borna/virologia
Escalas de Graduação Psiquiátrica Breve
Estudos de Casos e Controles
Feminino
Seres Humanos
Lituânia/epidemiologia
Masculino
Prevalência
Transtornos Psicóticos/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE


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[PMID]:27498995
[Au] Autor:Ando T; Takino T; Makita K; Tajima M; Koiwa M; Hagiwara K
[Ad] Endereço:Ishikari Agricultural Mutual Relief Association, Hokkaido 067-0055, Japan.
[Ti] Título:Sero-epidemiological analysis of vertical transmission relative risk of Borna disease virus infection in dairy herds.
[So] Source:J Vet Med Sci;78(11):1669-1672, 2016 Dec 01.
[Is] ISSN:1347-7439
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Borna disease virus (BDV) is a virus that causes a neurological disease in domestic animals, including a variety of animal species in Japan. Few studies have examined the mode of transmission of this virus in cattle, and the exact mechanisms underlying the transmission of the virus need to be elucidated. This study aimed to examine the contribution of vertical transmission of the virus, which occurs when the virus is transmitted from the mother to offspring during gestation or birth. We used an epidemiological approach. The relative risk (RR) was calculated for cattle born to BDV sero-positive cows from farms with a higher within-herd prevalence of BDV (56.8%). We tested the sera of 1,122 dairy cattle from 24 dairy herds in Hokkaido Prefecture, Japan, for BDV infection using the ELISA and western blotting method. The overall level of BDV sero-prevalence was 22.1%. Seroprevalence was significantly higher in closed-breeding herds that do not have buying in cows (39.7%) than in farms that restock cattle by buying in cows (4.4%, P<0.01). The overall RR of BDV vertical transmission from infected mothers to their daughters was 1.86 (95% confidence interval (CI): 1.54-2.56). Our results show that vertical transmission contributes significantly to BDV transmission in the farms tested in this study.
[Mh] Termos MeSH primário: Doença de Borna/transmissão
Doenças dos Bovinos/transmissão
Transmissão Vertical de Doença Infecciosa/veterinária
[Mh] Termos MeSH secundário: Criação de Animais Domésticos/métodos
Animais
Doença de Borna/epidemiologia
Vírus da Doença de Borna
Bovinos
Doenças dos Bovinos/epidemiologia
Feminino
Japão/epidemiologia
Prevalência
Estudos Soroepidemiológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160809
[St] Status:MEDLINE


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[PMID]:27212192
[Au] Autor:Tizard I; Ball J; Stoica G; Payne S
[Ad] Endereço:Department of Veterinary Pathobiology and the Schubot Exotic Bird Health Center,Texas A&M University,College of Veterinary Medicine and Biomedical Sciences,College Station,Texas 77843,USA.
[Ti] Título:The pathogenesis of bornaviral diseases in mammals.
[So] Source:Anim Health Res Rev;17(2):92-109, 2016 Dec.
[Is] ISSN:1475-2654
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.
[Mh] Termos MeSH primário: Doença de Borna/patologia
Vírus da Doença de Borna
Mamíferos
[Mh] Termos MeSH secundário: Animais
Doença de Borna/epidemiologia
Doença de Borna/virologia
Europa (Continente)/epidemiologia
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170823
[Lr] Data última revisão:
170823
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160524
[St] Status:MEDLINE
[do] DOI:10.1017/S1466252316000062


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[PMID]:26923969
[Au] Autor:Honda T
[Ad] Endereço:Department of Viral Oncology, Institute for Virus Research, Kyoto University.
[Ti] Título:Neuropathogenesis of persistent infection with Borna disease virus.
[So] Source:Uirusu;65(1):145-54, 2015.
[Is] ISSN:0042-6857
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:Borna disease virus (BDV), belonging to the non-segmented, negative-stranded RNA viruses, persistently infects the central nervous system of many mammals. Neonatal BDV infection in rodent models induces neurodevelopmental disturbance without overt inflammatory responses, resulting in a wide range of neurobehavioral abnormalities, such as anxiety, abnormal play behaviors, and cognitive deficits, resembling those of autism patients. Therefore, studies of BDV could provide a valuable model to investigate neuropathogenesis of neurodevelopmental disorders. However, the detailed neuropathogenesis of BDV has not been revealed. Here, we proposed two novel mechanisms that may contribute to BDV neuropathology. The first mechanism is abnormal IGF signaling. Using transgenic mice expressing BDV P protein in glial cells (P-Tg) that show neurobehavioral abnormalities resembling those in BDV-infected animals, we found that the upregulation of insulin-like growth factor (IGF) binding protein 3 in the astrocytes disturbs the IGF signaling and induces the Purkinje cell loss in BDV infection. The other is the integration of BDV sequences into the host genome. We recently found that BDV mRNAs are reverse-transcribed and integrated into the genome of infected cells. BDV integrants have the potential to produce their translated products or piRNAs, suggesting that BDV might exhibit the pathogenicity thorough these molecules. We also demonstrated that BDV integrants affect neighboring gene expression. Collectively, BDV integrants may alter transcriptome of infected cells, affecting BDV neuropathology.
[Mh] Termos MeSH primário: Doença de Borna/virologia
Vírus da Doença de Borna/patogenicidade
Transtornos do Neurodesenvolvimento/virologia
[Mh] Termos MeSH secundário: Animais
Astrócitos/metabolismo
Modelos Animais de Doenças
Seres Humanos
Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo
Camundongos
Camundongos Transgênicos
Células de Purkinje/patologia
Transdução de Sinais
Somatomedinas
Transcriptoma
Integração Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Insulin-Like Growth Factor Binding Protein 3); 0 (Somatomedins)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160301
[St] Status:MEDLINE
[do] DOI:10.2222/jsv.65.145


  10 / 560 MEDLINE  
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[PMID]:26287181
[Au] Autor:Liu S; Bode L; Zhang L; He P; Huang R; Sun L; Chen S; Zhang H; Guo Y; Zhou J; Fu Y; Zhu D; Xie P
[Ad] Endereço:Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. 18983145528@163.com.
[Ti] Título:GC-MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons.
[So] Source:Int J Mol Sci;16(8):19347-68, 2015 Aug 17.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC-MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V-infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.
[Mh] Termos MeSH primário: Doença de Borna/metabolismo
Vírus da Doença de Borna/metabolismo
Encéfalo/virologia
Neurônios/metabolismo
Neurônios/virologia
Ratos/virologia
[Mh] Termos MeSH secundário: Animais
Doença de Borna/patologia
Doença de Borna/virologia
Vírus da Doença de Borna/isolamento & purificação
Encéfalo/metabolismo
Encéfalo/patologia
Células Cultivadas
Feminino
Cromatografia Gasosa-Espectrometria de Massas
Seres Humanos
Metaboloma
Metabolômica
Neurônios/patologia
Ratos/metabolismo
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1605
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150820
[St] Status:MEDLINE
[do] DOI:10.3390/ijms160819347



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