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immunological studies of subacute measles encephalitis in ferrets: similarities to human subacute sclerosing panencephalitis.ferrets inoculated with subacute sclerosing panencephalitis virus strains d.r. and biken developed a subacute encephalitis. brain extracts, at neutral ph, from these ferrets showed high measles antibody titers, increased concentrations of immunoglobulin g (igg), and higher igg/albumin ratios than those of controls. although the brain extracts of subacute encephalitic animals showed significant synthesis of measles-specific igg (20 to 60% of the total igg) within the central nervous system, the e ...197939084
comparison of wild-type and subacute sclerosing panencephalitis strains of measles virus. neurovirulence in ferrets and biological properties in cell cultures.the neurovirulence of two wild type (wt) and seven subacute sclerosing panencephalitis (sspe) measles virus strains was tested in young adult ferrets by intracerebral (ic) inoculation of infected vero cell suspensions. wt strains edmonston and woodfolk and sspe strains mantooth, halle, and lec-s did not produce a detectable encephalitis in the ferrets, but caused a significant formation of serum antibodies against measles virus. sspe strains lec, ip-3, biken, and d.r., on the other hand, were al ...1978702052
a non-productive subacute sclerosing panencephalitis (sspe) virus of human and ferret: an ultrastructural study.a non-productive syncytiogenic measles virus isolated from the brain of an sspe patient was grown on vero cells. the ultrastructure of the infected syncytia was studied by electron microscopic and immunoperoxidase techniques. it was compared with the isolate of the virus after passage in ferrets, the edmonston strain of wild measles virus and the halle productive strain of sspe, all on vero cells. the immunoperoxidase labeling of the cell membranes of the edmonston measles virus infected cells w ...1976818871
growth of measles virus in nervous tissues. iii. neurovirulence of sspe virus in ferrets.the niigata-1 strain isolated from a patient with subacute sclerosing panencephalitis (sspe) was inoculated intracerebrally into ferrets. neurological signs developed in about 1 week in most of the animals. histopathological examinations of the central nervous tissues revealed degenerative lesions in the parenchyma of the brains and inflammatory reactions predominantly in the meninges and choroid plexus. virus antigen was demonstrated mainly in the nerve cells by immunofluorescent staining. the ...19751165608
transmission of measles virus encephalitis to ferrets by intracardiac inoculation of a cell-associated sspe virus strain.ferret fibroblasts infected with a cell-associated strain of subacute sclerosing panencephalitis virus were inoculated into the hearts of ferrets in order to study whether the virus can spread from the blood to the brain in this animal model. five of 21 inoculated ferrets developed encephalitis 5-7 days later and were sacrificed. sick animals showed inflammatory lesions in the brain, both perivascular cuffings and infiltration of inflammatory cells in the choroid plexus and meninges. virus was i ...19883214585
demonstration of immunoglobulin in brains of ferrets inoculated with an sspe strain of measles virus: use of protein a conjugated to horseradish peroxidase.measles virus-specific immunoglobulin g (igg) has been found in the brains of patients with subacute sclerosing panencephalitis (sspe), a slowly progressing central nervous system (cns) disease affecting children. igg/albumin ratios indicate that the antibodies are probably synthesized in the cns. in a ferret model system, protein a conjugated to horseradish peroxidase (prapx) was used to localize ig's in brains of animals inoculated with a cell associated strain of sspe. ig's were found in plas ...19853883686
passage in ferrets of encephalitogenic cell-associated measles virus isolated from brain of a patient with subacute sclerosing panencephalitis. 19734574999
cell fusion by canine distemper virus-infected cells.av3 cells (continuous human amnion) infected with the onderstepoort strain of canine distemper virus produced cell fusion within 2 to 5 hr when added to av3 cell monolayers. an apparent requirement for intact, infected cells was demonstrated by showing that (i) frozen-and-thawed infected cells failed to induce fusion, (ii) infected cells frozen in the presence of glycerol retained their ability to induce fusion, (iii) infected cells subjected to swelling in hypotonic buffer and homogenization lo ...19724644630
absence of m protein in a cell-associated subacute sclerosing panencephalitis virus.measles virus has been suggested to cause subacute sclerosing panencephalitis (sspe), a slow central nervous system disease of children. however, several questions remain about the pathogenesis of sspe. for example, it is not known whether alteration of the measles virus genome has a role in the initiation and persistence of the disease. several studies have compared the rna and protein composition of wild-type (wt) and sspe strains of measles virus in a search for markers characteristic of the ...19806772958
pathogenesis of viral encephalitis: demonstration of viral antigen(s) in the brain endothelium.one of the enigmas in the pathogenesis of inflammation is why the white cells adhere to the endothelium. in trying to define the pathogenic mechanism, we carried out experiments on ferrets infected with an sspe strain of measles virus. using immunoperoxidase labeling techniques, viral antigens were demonstrated on the luminal surface and in the cytoplasm of endothelial cells, irrespective of the presence or absence of inflammatory changes. the degree of inflammation corresponded well with antibo ...19836880611
presence of oligoclonal immunoglobulin g bands and lack of matrix protein antibodies in cerebrospinal fluids and sera of ferrets with measles virus encephalitis.young adult ferrets were immunized with measles vaccine and 5 to 6 weeks later inoculated intracerebrally with vero cells persistently infected with cell-associated strain d.r. of measles virus isolated from a patient with subacute sclerosing panencephalitis. of nine ferrets which survived the infection for 3 weeks or longer, five showed neurological signs. at the time of death they had widespread inflammation in their brains, and cell-associated virus was isolated from three ferrets sacrificed ...19836885159
immunolabeling of sspe and wild-type measles viruses in ferret brain cell culture.immunocytochemical studies using horseradish peroxidase labeled antibody were undertaken in an attempt to determine whether there are detectable antigenic differences which correlate with the biological properties of differences which correlate with the biological properties of different strains of sspe and wild-type measles virus grown in ferret bran cell cultures. the rabbit anti-measles hyperimmune serum used in this experiment contained antibodies to all the measles virus proteins when teste ...19806998252
comparative cytopathology of canine distemper and measles viruses in ferret kidney cell cultures. 196414184624
nearby clusters of hemagglutinin residues sustain slam-dependent canine distemper virus entry in peripheral blood mononuclear cells.signaling lymphocytic activation molecule (slam, cd150) is the universal morbillivirus receptor. based on the identification of measles virus (mv) hemagglutinin (h) amino acids supporting human slam-dependent cell entry, we mutated canine distemper virus (cdv) h and identified residues necessary for efficient canine slam-dependent membrane fusion. these residues are located in two nearby clusters in a new cdv h structural model. to completely abolish slam-dependent fusion, combinations of mutati ...200515827201
canine distemper virus uses both the anterograde and the hematogenous pathway for neuroinvasion.canine distemper virus (cdv), a member of the morbillivirus genus that also includes measles virus, frequently causes neurologic complications, but the routes and timing of cdv invasion of the central nervous system (cns) are poorly understood. to characterize these events, we cloned and sequenced the genome of a neurovirulent cdv (strain a75/17) and produced an infectious cdna that expresses the green fluorescent protein. this virus fully retained its virulence in ferrets: the course and signs ...200616973542
paramyxovirus infections in ex vivo lung slice cultures of different host species.paramyxoviruses, including measles virus (mv), human metapneumovirus (hmpv), human respiratory syncytial virus (hrsv) and canine distemper virus (cdv), are transmitted via the respiratory route. despite their close phylogenetic relationship, the pathogenesis of these viruses is very different. to study viral tropism and replication ex vivo, a protocol for the inflation of lungs with low-melting-point agarose mixed with culture medium was established. lung slices were prepared and remained viable ...201323777750
canine distemper virus epithelial cell infection is required for clinical disease but not for immunosuppression.to characterize the importance of infection of epithelial cells for morbillivirus pathogenesis, we took advantage of the severe disease caused by canine distemper virus (cdv) in ferrets. to obtain a cdv that was unable to enter epithelial cells but retained the ability to enter immune cells, we transferred to its attachment (h) protein two mutations shown to interfere with the interaction of measles virus h with its epithelial receptor, human nectin-4. as expected for an epithelial receptor (epr ...201222278252
morbillivirus control of the interferon response: relevance of stat2 and mda5 but not stat1 for canine distemper virus virulence in ferrets.the v proteins of paramyxoviruses control the innate immune response. in particular, the v protein of the genus morbillivirus interferes with the signal transducer and activator of transcription 1 (stat1), stat2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. to characterize the contributions of these pathways to canine distemper virus (cdv) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus v protein with ...201424371065
an orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. the related, zoonotic canine distemper virus (cdv) induces morbillivirus disease in ferrets with 100% lethality. we report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral rna polymerase. prophylactic oral treatment of ferrets infected intranasally with a lethal cdv dose reduced viremia and prolonged survival. ferrets infected with the same ...201424739760
morbillivirus experimental animal models: measles virus pathogenesis insights from canine distemper virus.morbilliviruses share considerable structural and functional similarities. even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. thus, insights gained with one morbillivirus often apply to the other members of the genus. since the canine distemper virus (cdv) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate ...201627727184
canine distemper matrix protein modulates particle infectivity, particle composition, and envelope distribution in polarized epithelial cells, and virulence.in paramyxoviruses, the matrix (m) protein mediates the interaction between the envelope and internal proteins during particle assembly and egress. in measles virus (mev), m mutations such as in those found in sspe strains, and differences in vaccine and wild type m proteins can affect the strength of interaction with the envelope glycoproteins, assembly efficiency, and spread. however, the contribution of the m protein to virus replication and pathogenesis of the closely related canine distempe ...201121543493
disease manifestations of canine distemper virus infection in ferrets are modulated by vitamin a status.the measles virus (mv) causes half a million childhood deaths annually. vitamin a supplements significantly reduce measles-associated mortality and morbidity. the mechanisms whereby vitamin a acts against mv are not understood and currently there is no satisfactory small animal model for mv infection. we report on the development of a ferret model to study antiviral activity of vitamin a against canine distemper virus (cdv). cdv is closely related to mv at the molecular level and distemper in fe ...200717634264
genetic diversity of the attachment (h) protein gene of current field isolates of canine distemper virus.to characterize the variability of recent field isolates of canine distemper virus (cdv) from different hosts and geographical areas, we conducted nucleotide sequence analysis of the gene encoding the haemagglutinin (h), the attachment protein of this virus. pronounced differences between field isolates were revealed in comparison to the convac and onderstepoort vaccine strains. the diversity of cdv appeared to exceed that determined for measles virus. phylogenetic analysis also separated the fi ...19979018059
the pathogenesis of crohn's disease.this paper describes a program of research undertaken by the inflammatory bowel disease study group at the royal free hospital school of medicine. the group has tested the hypothesis that the primary pathological abnormality in crohn's disease is in the mesenteric blood supply. the first experiments involved microcorrosion resin casting of the arterial supply of specimens of resected intestine affected by crohn's disease. this revealed severe damage to submucosal blood vessels, even in areas tha ...19947921140
distemper virus infection in ferrets: an animal model of measles-induced immunosuppression.distemper virus is very similar antigenically to measles virus, and the disease produced in ferrets by distemper is a systemic illness quite similar to measles infection in humans. using an attenuated strain of distemper virus, we produced a mild systemic illness in ferrets and were able to study the effects of the viral infection on cell-mediated immunity (cmi). beginning on day 5 after viral inoculation and continuing to day 30, infected ferrets showed a marked lymphopenia, with a reduction in ...19827044625
measles virus encephalitis in ferrets as a model for subacute sclerosing panencephalitis.young adult ferrets were used as experimental animals to study subacute sclerosing panencephalitis (sspe). when cells infected with cell-associated measles virus strains isolated from sspe patients were inoculated intracerebrally (i.c.) into ferrets, they developed an acute encephalitis and died within 1 to 3 weeks without detectable antibody formation. immunization with live measles vaccine 5 weeks before i.c. inoculation changed the course of the infection in about 50% of the ferrets. these an ...19854021436
localization of measles virus antigens in subacute sclerosing panencephalitis in ferrets.young adult male ferrets were inoculated intracerebrally (i.c.) with a cell-associated encephalitogenic subacute sclerosing panencephalitis (sspe) virus strain to study the pathogenesis of the disease at the ultrastructural level. most became acutely ill in 8-13 days. areas of the brain were examined with indirect immunoperoxidase labeling techniques to detect measles antigen. none of these animals showed the characteristic viral nucleocapsids or marked inflammatory response associated with sspe ...19853894788
measles virus matrix protein gene expression in a subacute sclerosing panencephalitis patient brain and virus isolate demonstrated by cdna hybridization and immunocytochemistry.subacute sclerosing panencephalitis (sspe) is a rare, fatal disease of children caused by a persistent measles virus infection of the central nervous system. a defect in synthesis of measles virus matrix (m) protein may be a factor in virus persistence in the brain. this study details attempts to detect expression of m protein in the brain of an sspe patient, in the cell-associated virus isolated from this brain, and in brains of ferrets inoculated with the isolate. in situ hybridization with a ...19873324622
measles antibodies and immunoglobulins in sera from patients with subacute sclerosing panencephalitis (sspe) and from an infected ferret.cellulose acetate electrophoresis of sera from 2 patients with sspe revealed a slow-moving and a fast-moving gamma-globulin band. the igg fractions from sera were isolated by the combination of starch block electrophoresis, sephadex gel filtration and isoelectric focusing techniques. the purity of each protein was tested by immunoelectrophoresis using a potent goat anti-whole human serum. the isolated igg preparations were tested in hi, cf and n tests against measles virus envelope, measles viru ...19751185233
encephalitis in ferrets caused by a nonproductive strain of measles virus (d.r.) isolated from patient with subacute sclerosing panencephalitis.a nonproductive, syncytiogenic strain (d.r.) of measles virus, isolated from a patient with subacute sclerosing panencephalitis (sspe), was inoculated intracerebrally into ferrets in an attempt to induce subacute encephalitis. inoculation of freeze-thawed syncytia before immunization was the least effective procedure, and inoculation of live syncytia after immunization with measles virus vaccine was the most effective procedure, for induction of subacute or persistent subclinical encephalitis in ...1977894077
ultrastructural and histological studies of brains of ferrets inoculated with subacute sclerosing panencephalitis: similarities to human disease.similarities to human subacute sclerosing panencephalitis (sspe) were revealed in a study of the brains of ferrets inoculated with a cell associated measles virus originally isolated from an sspe patient. the similarities were greatest in animals that showed neurological signs 3-4 months after inoculation and had high titers of neutralizing antibodies against measles virus. these included dense core particles, nuclear bodies, alterations of basement membranes of small blood vessels, plasma cells ...1977886366
a chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.cdv infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles moraten vaccine strain with the envelope of a recent cdv wild type isolate. the resulting virus did not cause disease or immunosuppression in ferrets and conferred protect ...200919540272
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