RESUMEN
Members of the family Bornaviridae produce enveloped virions containing a linear negative-sense non-segmented RNA genome of about 9 kb. Bornaviruses are found in mammals, birds, reptiles and fish. The most-studied viruses with public health and veterinary impact are Borna disease virus 1 and variegated squirrel bornavirus 1, both of which cause fatal encephalitis in humans. Several orthobornaviruses cause neurological and intestinal disorders in birds, mostly parrots. Endogenous bornavirus-like sequences occur in the genomes of various animals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Bornaviridae, which is available at ictv.global/report/bornaviridae.
Asunto(s)
Virus de la Enfermedad de Borna/clasificación , Bornaviridae/clasificación , Animales , Enfermedad de Borna/virología , Virus de la Enfermedad de Borna/genética , Virus de la Enfermedad de Borna/fisiología , Virus de la Enfermedad de Borna/ultraestructura , Bornaviridae/genética , Bornaviridae/fisiología , Bornaviridae/ultraestructura , Genoma Viral , Especificidad del Huésped , Humanos , Virión/ultraestructura , Replicación ViralRESUMEN
Structures of the nucleoprotein of three negative strand RNA virus families, borna disease virus, rhabdovirus and influenza A virus, are now available. Structural comparisons showed that the topology of the RNA binding region from the three proteins is very similar. The RNA was shown to fit into a cavity formed by the two distinct domains of the RNA binding region in the rhabdovirus nucleoprotein. Two helices connecting the two domains characterize the center of the cavity. The nucleoproteins contain at least 5 conserved helices in the N-terminal domain and 3 conserved helices in the C-terminal domain. Since all negative strand RNA viruses are required to have the ribonucleoprotein complex as their active genomic templates, it is perceivable that the (5H+3H) structure is a common motif in the nucleoprotein of negative strand RNA viruses.
Asunto(s)
Virus de la Enfermedad de Borna/química , Virus de la Influenza A/química , Proteínas de la Nucleocápside/química , Nucleoproteínas/química , Virus ARN/química , Rhabdoviridae/química , Secuencia de Aminoácidos , Sitios de Unión , Virus de la Enfermedad de Borna/ultraestructura , Virus de la Influenza A/ultraestructura , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Virus ARN/ultraestructura , ARN Viral/química , Proteínas de Unión al ARN/química , Rhabdoviridae/ultraestructuraRESUMEN
The matrix protein M of Borna disease virus (BDV) is a constituent of the viral envelope covering the inner leaflet of the lipid bilayer. BDV-M was expressed as recombinant protein in Escherichia coli, purified to homogeneity and structurally analyzed. Recombinant M (i) forms non-covalently bound multimers with a Stoke's radius of 35 Angstroms estimated by size exclusion chromatography, (ii) consists of tetramers detected by analytical ultracentrifugation, and (iii) appears by electron microscopy studies as tetramers with the tendency to assemble into high molecular mass lattice-like complexes. The structural features suggest that BDV-M possesses a dominant driving force for virus particle formation.
Asunto(s)
Virus de la Enfermedad de Borna/química , Virus de la Enfermedad de Borna/fisiología , Proteínas de la Matriz Viral/química , Proteínas de la Matriz Viral/metabolismo , Ensamble de Virus/fisiología , Virus de la Enfermedad de Borna/genética , Virus de la Enfermedad de Borna/ultraestructura , Cromatografía en Gel , Clonación Molecular , Reactivos de Enlaces Cruzados/metabolismo , Electroforesis en Gel de Poliacrilamida , Desnaturalización Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Ultracentrifugación , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/aislamiento & purificación , Proteínas de la Matriz Viral/ultraestructuraRESUMEN
A 'disease of the head' affecting horses, as described in the 17th Century is now known as Borna disease. Research over the past 100 years has established that the aetiological agent, Borna disease virus (BDV), is an unsegmented, single- and negative-stranded, enveloped ribonucleic acid (RNA) virus which represents the family Bornaviridae in the order Mononegavirales. The virus exists world-wide in horses, sheep, cattle, cats, dogs and ostriches. The infection can be fatal, but the majority of carriers are persistently infected without showing symptoms. The association with psychiatric diseases in humans led to an international explosion of research on BDV, with centres established in Germany, the United States of America and Japan. Experimental infections of tree shrews and rats served to examine the effects of persistent and overt disease, most excitingly, virus-induced behavioural changes, and emotional and learning deficits. This 'emerging' virus infection shows complex pathogenetic mechanisms in the nervous system, but also spreads through myelo-monocytic cells. Diagnosis can be made serologically, but detection of antigen markers in peripheral white blood cells, combined with nucleic acid amplification is more profitable. Comparative RNA studies reveal an unusually high genetic homology of viruses. Isolates recovered from humans and equines suggest species-specificity. Vaccination is not an advisable strategy, but antiviral therapy, especially with amantadine sulphate, promises efficacy in human mood disorders, and is effective in vitro. Infections with BDV follow a vulnerability principle to cause disease. Although cross-species transmission of this commensal virus has not been proven, zoonotic aspects of BDV should be carefully considered.
Asunto(s)
Enfermedad de Borna/virología , Virus de la Enfermedad de Borna , Zoonosis , Animales , Enfermedades de las Aves/epidemiología , Enfermedades de las Aves/virología , Enfermedad de Borna/diagnóstico , Enfermedad de Borna/epidemiología , Enfermedad de Borna/terapia , Virus de la Enfermedad de Borna/química , Virus de la Enfermedad de Borna/fisiología , Virus de la Enfermedad de Borna/ultraestructura , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/virología , Gatos , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/virología , Pollos , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/virología , Perros , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/virología , Caballos , Humanos , Conejos , Ratas , Ovinos , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/virología , Struthioniformes , Zoonosis/epidemiología , Zoonosis/virologíaRESUMEN
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.
Asunto(s)
Virus de la Enfermedad de Borna/ultraestructura , Animales , Virus de la Enfermedad de Borna/aislamiento & purificación , Línea Celular , Perros , Morfogénesis , ARN Viral/análisis , Virión/aislamiento & purificaciónRESUMEN
The unique genetic and biological properties of this small enveloped RNA virus indicate that Borna disease virus (BDV) is an evolutionary old pathogen. It appears perfectly adapted to persist inside the limbic system, a most delicate and sensitive old area of the mammalian brain involved in the control of mood, behavior, and memory. In many infected individuals, BDV remains a commensal during their lifetime. In a minority of vulnerable subjects, BDV becomes frequently activated, leading to episodes of distinct, more or less severe disturbances of information processing, behavioral and mood alterations. BDV research in humans is anticipated to initiate new insights into the interplay of exogenous and endogenous factors governing mood disorders. In nature BDV preferentially behaves as a neurotropic virus, but may latently and/or persistently infect cells of the reticuloendothelial system. This has been shown to be of great diagnostic importance, because now BDV 'footprints' can be followed in vivo in animals and man. BDV, which has long been considered as a classical animal virus, is present in humans, and has been found to be associated with some defined psychiatric disorders in particularly vulnerable individuals. An interaction of BDV proteins with neurotransmitter activities is plausible in the light of experimental animal data. Interference with normal behavior and the influence on mood and cognitive functions as demonstrated in animals and assumed in humans require extensive future research on the molecular etiopathogenesis. Aside from these clinical aspects, BDV is an unusual agent with outstanding features, namely replication in the nucleus of its target cells by an elusive, partially unknown mechanism, showing no cytopathogenicity or disturbance of vital cell functions, but altering luxury functions, and with a lifelong persistence giving rise to periods of long latency and short activation.
Asunto(s)
Enfermedad de Borna/fisiopatología , Animales , Enfermedad de Borna/inmunología , Enfermedad de Borna/virología , Virus de la Enfermedad de Borna/inmunología , Virus de la Enfermedad de Borna/aislamiento & purificación , Virus de la Enfermedad de Borna/patogenicidad , Virus de la Enfermedad de Borna/ultraestructura , HumanosRESUMEN
The etiological agent of Borna disease, a persistent virus infection of the central nervous system with differently expressed symptomatology, was morphologically unknown. Here we provide the first convincing data on its phenotypic architecture. Salt-released virus comprising the biological parameters of Koch's postulates has an unsegmented single-stranded RNA. A dense band (1.22 g/cm3) in CsCl contains 90-nm particles which appear to be enveloped and a fraction of 50- to 60-nm particles. Labeling of the virions with neutralizing antisera and colloidal gold conjugates indicates that the 90-nm particles most likely represent the causative agent.
Asunto(s)
Virus de la Enfermedad de Borna/genética , Virus de la Enfermedad de Borna/ultraestructura , Genoma Viral , ARN Viral/ultraestructura , Animales , Aves , Gatos , Línea Celular , Sistema Libre de Células , Ensayo de Inmunoadsorción Enzimática , Caballos , Microscopía Inmunoelectrónica/métodos , Oligodendroglía , ARN Viral/análisis , Ovinos , Virión/genética , Virión/ultraestructuraRESUMEN
A line of Madin Darby canine kidney (MDCK) cells persistently infected with Borna disease virus was examined by electron microscopy. Thin sections revealed the presence of intracytoplasmic virus-like particles ranging from 50-100 nm in diameter. Nuclei of the infected cells exhibited accumulation of electron-dense granular structures 15-18 nm in diameter. The intracytoplasmic particles were roughly spherical with a limiting membrane, suggesting the presence of a lipid-containing envelope. The internal structure consisted of strand-like material which in some cases was condensed underneath the envelope. The possible relationship of these particles to Borna disease virions is discussed.
Asunto(s)
Virus de la Enfermedad de Borna/ultraestructura , Núcleo Celular/virología , Citoplasma/virología , Cuerpos de Inclusión Viral/ultraestructura , Animales , Virus de la Enfermedad de Borna/crecimiento & desarrollo , Línea Celular , Perros , Células Epiteliales , Riñón , Microscopía Electrónica , Virión/ultraestructuraRESUMEN
Borna disease virus infected rabbits were chosen to search for electronmicroscopic structures. Intensively investigated hippocampal neurons showed intranuclear inclusions; 100 nm particle-like structures surrounded by 20 nm granular forms were prominent. In connection with elsewhere reported in situ hybridization studies of virus-specific RNA to areas of the Joest-Degen inclusions we suggest that these particle structures may represent Borna virus. Jost-Degen (8) found intranuclear inclusion bodies in neurons to be pathognomonic for Borna disease (BD) in the horse. Half a century later these structures were suggested to represent BD virus (BDV)-specific antigen aggregates (15). A century later we characterized the virus to contain a single and negative stranded RNA of 8.5 kb, which transcribes in the nucleus (5) and could show that virus complementary RNA seems to hybridize spot-like to nuclear areas, probably representing the Jost-Degen inclusions (7). Electron microscopic (EM) findings on structures in BDV infected brain cells and about particle-like structures obtained from infected tissue culture cells have been reported by different groups (1, 2, 3, 4, 5, 6, 9, 11, 12, 13). The demonstration of crystalline aggregates and filament bundles in the cytoplasma and karyospheridia (nuclear bodies) were prominent. Such structures were seen in infected rabbits, hamsters, rats mice and naturally infected horses. The phenotypic description of filamentous structures, crystalline aggregates in the cytoplasma and large karyospheridia were prominent. Based on our experience with BDV infections in rabbits we selected this species for ultrastructural studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedad de Borna/patología , Virus de la Enfermedad de Borna/ultraestructura , Cuerpos de Inclusión Viral/ultraestructura , Neuronas/ultraestructura , Conejos , Animales , Enfermedad de Borna/microbiología , Microscopía ElectrónicaRESUMEN
BACKGROUND: Rabies and Borna disease viruses have been regarded as classical neurotropic agents. Many pathogenetic similarities are shared by these two negative strand RNA viruses. In view of recently gained data on the virology and pathology of these two diseases, and up-to-date comparative pathogenetic study seems to be justified. EXPERIMENTAL DESIGN: This study is based on a survey of experimental and natural infections of laboratory animals and natural hosts. The morphologic damage to the nervous system has been evaluated by light and electron microscopy, with special emphasis on immunocytochemical methods. RESULTS: This comparative study disclosed that both viruses are transported inside axons, pass synapses and propagate along neuronal networks. At the sites of synaptic transfer, full virus particles can never be detected in the early phase of rabies virus infection; in Borna disease virus (BDV) infection, virus particles cannot be found in any phase of disease progression. Thus, a major difference exists between the two agents insofar as rabies virus is morphologically well characterized, whereas BDV has never been visualized in tissue sections. Furthermore, rabies virus infects only neurons, whereas BDV also infects glial cells. The host range and the scale of infection of extraneural tissues by both agents is extremely similar. CONCLUSIONS: These observations allow us to postulate that the synaptic transfer of both viruses likely ensures in the form of bare nucleocapsids (ribonucleoprotein-transcriptase complexes). While in the later phases of replication complete rabies virions are regularly assembled, BDV propagates within the central nervous system in an incomplete form, so that it remains morphologically imperceptible. Thus, BDV may appear in a complete, enveloped form only when exiting the host organism. The dissemination patterns of the two agents may be influenced by specific affinities to neurotransmitter receptor sites. It remains unresolved, why BDV readily infects non-neuronal central nervous system cells, while rabies virus remains restricted to neuronal elements.