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prevalence of naturally occurring viral infections, mycoplasma pulmonis and clostridium piliforme in laboratory rodents in western europe screened from 2000 to 2003.in this report prevalence rates of rodent viruses in laboratory animals are presented based on routine serological screening of mouse and rat colonies from european institutes. the prevalences found during the period 2000-2003 are compared with those reported for 1981-1984 and 1990-1993. it is shown that some infections were eliminated from laboratory animal colonies (e.g. k-virus and polyomavirus) by taking preventative measures whereas other infections such as mouse hepatitis virus and parvovi ...200616600073
studies on pneumonia virus of mice (pvm) : ii. immunological evidence of latent infection with the virus in numerous mammalian species.the results of neutralization tests with pvm and serum obtained from numerous animal species indicate that antibodies agaiust this virus were present in the blood of all mammalian species tested, as not in that of fowls, and that their incidence in various species was widely different. they indicate, also, that in certain species, particularly the cotton rat, there were marked seasonal variations in the incidence of such antibodies; in the late winter and spring the incidence was much higher tha ...194619871515
stimulation of pneumovirus-specific cd8+ t-cells using a non-toxic recombinant ricin delivery system.internalisation of the plant toxin ricin occurs by retrograde transport which delivers the toxin to the er where it intersects with the mhc class i system for peptide antigen display. here, we describe the generation of an inactivated, non-toxic, ricin molecule fused to a peptide which elicits a cd8+ t-cell response in mice directed against pneumonia virus of mice, a pneumovirus related to human respiratory syncytial virus. the ricin fusion elicited a significant t-cell response when delivered b ...200716650896
effect of adrenal hormones on infection of mice with pneumonia virus of mice (pvm). 195114911933
diminished inflammatory responses to natural pneumovirus infection among older mice.immune responses to virus infection undergo significant change as part of the aging process. here we examine the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (pvm). although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators, including mip-1alpha, je/mcp-1, ifn-gamma and ifn-gamma-induced mig and ip-10, and interleukins (il)-6 and il-17. levels of ...200717655904
roles of the pvm m2-1, m2-2 and p gene orf 2 (p-2) proteins in viral replication.a plasmid-based reverse genetics system for pneumonia virus of mice (pvm) using a synthetic minigenome is described. the system was used to investigate the functions of several viral proteins. the m2-1 protein of pvm was shown to enhance reporter gene expression when present at low levels, similar to the situation for the equivalent respiratory syncytial virus (rsv) m2-1 protein, but at high levels was shown to reduce gene expression from the minigenome activity, which differs significantly form ...200817881076
concurrent infection with influenza virus and mumps virus or pneumonia virus of mice as bearing on the inhibition of virus multiplication by bacterial polysaccharides.preexisting infection with pvm or mumps virus does not prevent multiplication of the virus of influenza a or b in the same tissue. similarly, pre-existing infection with one or another of the influenza viruses does not prevent multiplication of either pvm or mumps virus in the same tissue. the failure of these two groups of viruses to interfere with the multiplication of each other is discussed in relation to the mechanism of inhibition of multiplication of mumps virus and pvm by the capsular po ...194918099164
the effect of diet on the susceptibility of the mouse to pneumonia virus of mice; influence of pyridoxine in the period after the inoculation of virus.young mice fed diets deficient in pyridoxine or fed desoxypyridoxine after the inoculation of the pneumonia virus of mice were more resistant to infection than well nourished controls. the susceptibility of young mice to pvm increased with the duration of pyridoxine administration after inoculation. dietary protein restriction when pyridoxine was provided did not affect the susceptibility of mice to pvm. the pvm-combining capacity of mouse lung and the titer of humoral antibody against pvm were ...194918107969
the effect of diet on the susceptibility of the mouse to pneumonia virus of mice; influence of pyridoxine administered in the period before as well as after the inoculation of virus.young mice fed diets deficient in pyridoxine for 8 days or longer before the inoculation of pvm, as well as after inoculation, were more susceptible to infection than control mice fed complete diets. young mice fed a pyridoxine-deficient diet gained weight as well as controls fed a complete diet for 5 weeks, but they lost weight in the 6th week. the ratio of thymus or spleen weight to body weight was less in mice fed a pyridoxine-deficient diet for 6 weeks than in controls fed a complete diet. h ...194918107970
pneumonia virus of mice: severe respiratory infection in a natural host.pneumonia virus of mice (pvm; family paramyxoviridae, genus pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial viruses. among the prominent features of this infection, robust replication of pvm takes place in bronchial epithelial cells in response to a minimal virus inoculum. virus replication in situ results in local production of proinflammatory cytokines (mip-1alpha, mip-2, mcp-1 and ifngamma) and granulocyte recruitment to the lung. if ...200818471897
functionally competent eosinophils differentiated ex vivo in high purity from normal mouse bone marrow.we have devised an ex vivo culture system which generates large numbers of eosinophils at high purity (>90%) from unselected mouse bone marrow progenitors. in response to 4 days of culture with recombinant mouse flt3-l and recombinant mouse stem cell factor followed by recombinant mouse il-5 alone thereafter, the resulting bone marrow-derived eosinophils (bmeos) express immunoreactive major basic protein, siglec f, il-5r alpha-chain, and transcripts encoding mouse eosinophil peroxidase, ccr3, th ...200818768855
role of t cells in virus control and disease after infection with pneumonia virus of mice.infection of mice with pneumonia virus of mice (pvm) is used as a natural host experimental model for studying the pathogenesis of infection with the closely related human respiratory syncytial virus. we analyzed the contribution of t cells to virus control and pathology after pvm infection. control of a sublethal infection with pvm strain 15 in c57bl/6 mice was accompanied by a 100-fold increase in pulmonary cytotoxic t lymphocytes, 20% of which were specific for pvm. t-cell-deficient mice fail ...200818815308
eosinophils and their interactions with respiratory virus pathogens.eosinophils are implicated in the pathophysiology of respiratory virus infection, most typically in negative roles, such as promoting wheezing and bronchoconstriction in conjunction with virus-induced exacerbations of reactive airways disease and in association with aberrant hypersensitivity responses to viral vaccines. however, experiments carried out in vitro and in vivo suggest positive roles for eosinophils, as they have been shown to reduce virus infectivity in tissue culture and promote cl ...200918818885
the antagonistic effect of certain substances of bacterial origin on the course of infection with pneumonia virus of mice (pvm). 194718917237
deletion of nonstructural proteins ns1 and ns2 from pneumonia virus of mice attenuates viral replication and reduces pulmonary cytokine expression and disease.pneumonia virus of mice (pvm) strain 15 causes fatal pneumonia in mice and provides a convenient model for human respiratory syncytial virus pathogenesis and immunobiology. we prepared pvm mutants lacking the genes for nonstructural proteins ns1 and/or ns2. in vero cells, which lack type i interferon (ifn), deletion of these proteins had no effect on the efficiency of virus growth. in ifn-competent mouse embryo fibroblasts, wild-type (wt) pvm and the deltans1 virus grew efficiently and strongly ...200919052095
interferon-gamma coordinates ccl3-mediated neutrophil recruitment in vivo.we have shown previously that acute infection with the respiratory pathogen, pneumonia virus of mice (pvm), results in local production of the proinflammatory chemokine, ccl3, and that neutrophil recruitment in response to pvm infection is reduced dramatically in ccl3 -/- mice.200919298652
pulmonary eosinophils and their role in immunopathologic responses to formalin-inactivated pneumonia virus of mice.enhanced disease is the term used to describe the aberrant th2-skewed responses to naturally acquired human respiratory syncytial virus (hrsv) infection observed in individuals vaccinated with formalin-inactivated viral ags. here we explore this paradigm with pneumonia virus of mice (pvm), a pathogen that faithfully reproduces features of severe hrsv infection in a rodent host. we demonstrate that pvm infection in mice vaccinated with formalin-inactivated ags from pvm-infected cells (pvm ags) yi ...200919542471
pneumoviruses infect eosinophils and elicit myd88-dependent release of chemoattractant cytokines and interleukin-6.eosinophils are recruited to the lung in response to infection with pneumovirus pathogens and have been associated with both the pathophysiologic sequelae of infection and, more recently, with accelerated virus clearance. here, we demonstrate that the pneumovirus pathogens, respiratory syncytial virus (rsv) and pneumonia virus of mice (pvm), can infect human and mouse eosinophils, respectively, and that virus infection of eosinophils elicits the release of disease-related proinflammatory mediato ...200919652202
studies on pneumonia virus of mice (pvm) : i. the precision of measurements in vivo of the virus and antibodies against it.this study on pneumonia virus of mice (pvm) was carried out in order to obtain as accurate data as possible on the degree of variation which may be expected in titrations of the virus or of antibodies against it in vivo. it is believed that the knowledge gained will facilitate further investigations on this latent pneumotropic virus and make possible a more exact assessment of the significance of experimental results obtained with the agent. the reproducibility of 50 per cent maximum score titra ...194619871514
mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and interferon-gamma receptor deficient mice.protective mechanisms underlying the responses to mucosal vaccination are not yet clearly defined. using the natural mouse pneumovirus pathogen, pneumonia virus of mice (pvm), we explore responses of wild type and interferon-gamma (ifngamma) receptor gene-deleted mice to virulent challenge after mucosal vaccination with an attenuated virus strain. serum neutralizing antibodies develop after intranasal inoculation with 30 pfu of attenuated, replication-competent pvm strain 15, which correlate wit ...200717052820
infectious microorganisms in mice (mus musculus) purchased from commercial pet shops in germany.in this study, we investigated the prevalence of infectious microorganisms (viruses, bacteria, fungi and eukaryotic parasites) in mice from different pet shops in germany; such animals may compromise the hygienic integrity of laboratory animal vivaria if private pet holders act as unintended vectors of infections carried by them. house mice sold as pets or feed specimens were purchased from different pet shops and tested for a comprehensive panel of unwanted microorganisms. we found a number of ...201121508117
microbiological monitoring of guinea pigs reared conventionally at two breeding facilities in korea.in this study, microbiological monitoring of guinea pigs reared conventionally in two facilities was performed twice in 2004, with a three-month-interval between surveys. this study was based on the recommendations of the felasa working group, with some modifications. in serological tests in the first survey, some animals from facility a showed positive results for encephalitozoon cuniculi, sendai virus, pneumonia virus of mice (pvm), and reovirus-3 (reo-3); facility b showed a positive result o ...200617090958
immunization strategies for the prevention of pneumovirus infections.pneumoviruses, which are viruses of the family paramyxoviridae, subfamily pneumovirinae, are pathogens that infect the respiratory tract of their host species. the human pneumovirus pathogen, human respiratory syncytial virus (rsv), has counterparts that infect cows (bovine rsv), sheep (ovine rsv), goats (caprine rsv) and rodents (pneumonia virus of mice). each pneumovirus is host specific and results in a spectrum of disease, ranging from mild upper-respiratory illness to severe bronchiolitis a ...200717408367
coupled translation of the second open reading frame of m2 mrna is sequence dependent and differs significantly within the subfamily pneumovirinae.coupled translation, first described in the m2 gene of pneumovirus respiratory syncytial virus (rsv), is an alternative mechanism of translational initiation in which the ribosomes which translate the first (m2-1) open reading frame (orf) move a short distance upstream after termination and reinitiate translation from a second (m2-2) overlapping orf. here, we show that the same mechanism occurs in two closely related viruses, avian pneumovirus (apv) and pneumonia virus of mice (pvm), although wi ...200717522208
efficient replication of pneumonia virus of mice (pvm) in a mouse macrophage cell line.pneumonia virus of mice (pvm; family paramyxoviridae, subfamily pneumovirinae) is a natural respiratory pathogen of rodent species and an important new model for the study of severe viral bronchiolitis and pneumonia. however, despite high virus titers typically detected in infected mouse lung tissue in vivo, cell lines used routinely for virus propagation in vitro are not highly susceptible to pvm infection. we have evaluated several rodent and primate cell lines for susceptibility to pvm infect ...200717547763
identification of a novel virulence factor in recombinant pneumonia virus of mice.pneumonia virus of mice (pvm) is a murine relative of human respiratory syncytial virus (hrsv). here we developed a reverse genetics system for pvm based on a consensus sequence for virulent strain 15. recombinant pvm and a version engineered to express green fluorescent protein replicated as efficiently as the biological parent in vitro but were 4- and 12.5-fold attenuated in vivo, respectively. the g proteins of hrsv and pvm have been suggested to contribute to viral pathogenesis, but this had ...200717567693
identification of a cd4 t cell epitope in the pneumonia virus of mice glycoprotein and characterization of its role in protective immunity.pneumonia virus of mice (pvm) causes bronchiolitis and pneumonia in mice. infection is associated with high levels of viral replication in the lungs and results in the functional inactivation of pulmonary virus-specific cd8 t cells. due to its similarity to severe human respiratory syncytial virus (rsv) infection, pvm infection in mice has been proposed as an alternative rsv model. here, we have delineated the minimal requirements for protective t cell immunity in the pvm model. immunization wit ...200717632195
the modifying effects of certain substances of bacterial origin on the course of infection with pneumonia virus of mice (pvm).evidence is presented which indicates that certain polysaccharide preparations derived from various bacterial species, as well as similar materials not of bacterial origin, are capable of lessening the severity of infection with pneumonia virus of mice (pvm) and inhibiting multiplication of the virus in mouse lungs infected with this agent. it seems probable that modification with respect to the virus is mediated by a substance which may be polysaccharide in nature.194719871640
the effect of sulfhydryl groups on pneumonia virus of mice (pvm).evidence is presented which indicates that pvm is affected adversely in concentrated lung tissue suspensions or in the presence of glutathione. because iodoacetamide inhibits or eliminates these effects in a similar manner, it is concluded that sulfhydryl groups are essential to their development.194719871685
studies on a lung tissue component which combines with pneumonia virus of mice (pvm).evidence has been obtained which indicates that the lung tissues of mammalian species susceptible to infection with pvm contain a specific component which combines with the virus. the concentration of this tissue component appears to be directly proportional to the suceptibility of the species; in its absence infection with pvm cannot be established. the available evidence suggests that the presence of the virus-combining component in lung tissue may play a decisive ro1e in the initiation of inf ...194719871686
helicobacter spp. in wild mice (peromyscus leucopus) found in laboratory animal facilities.wild rodents are a potential source for pathogen introduction into laboratory animal research facilities. a study was designed to assess wild mice found at our institution by infectious disease surveillance. wild white-footed mice (peromyscus leucopus) were captured with live capture traps placed in areas in which wild mice had been reported in several animal facilities. captured animals were euthanized by inhalation of co(2), blood was collected by cardiocentesis (n = 10), and necropsy was perf ...200919930823
granzyme a- and b-cluster deficiency delays acute lung injury in pneumovirus-infected mice.lower respiratory tract infection by the human pneumovirus respiratory syncytial virus is a frequent cause of acute lung injury in children. severe pneumovirus disease in humans is associated with activation of the granzyme pathway by effector lymphocytes, which may promote pathology by exaggerating proapoptotic caspase activity and proinflammatory activity. the main goal of this study was to determine whether granzymes contribute to the development of acute lung injury in pneumovirus-infected m ...201020018616
early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice.early-life respiratory viral infections, notably with respiratory syncytial virus (rsv), increase the risk of subsequent development of childhood asthma. the purpose of this study was to assess whether early-life infection with a species-specific model of rsv and subsequent allergen exposure predisposed to the development of features of asthma.201020122285
studies on pneumonia virus of mice (pvm); the precision of measurements in vivo of the virus and antibodies against it. 194621007274
studies on pneumonia virus of mice (pvm); immunological evidence of latent infection with the virus in numerous mammalian species. 194621007275
studies on pneumonia virus of mice (pvm); hemagglutination by the virus; the occurrence of combination between the virus and a tissue substance. 194621010048
inflammatory responses to acute pneumovirus infection in neonatal mice.the innate immune responses of neonates differ dramatically from those of adults. here we examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (pvm), a rodent pathogen (family paramyxoviridae, genus pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection.201021078159
lactobacillus-mediated priming of the respiratory mucosa protects against lethal pneumovirus infection.the inflammatory response to respiratory virus infection can be complex and refractory to standard therapy. lactobacilli, when targeted to the respiratory epithelium, are highly effective at suppressing virus-induced inflammation and protecting against lethal disease. specifically, wild-type mice primed via intranasal inoculation with live or heat-inactivated lactobacillus plantarum or lactobacillus reuteri were completely protected against lethal infection with the virulent rodent pathogen, pne ...201021169550
both nonstructural proteins ns1 and ns2 of pneumonia virus of mice are inhibitors of the interferon type i and type iii responses in vivo.infection of mice with pneumonia virus of mice (pvm) provides a convenient experimental pathogenesis model in a natural host for a human respiratory syncytial virus-related virus. extending our previous work showing that the pvm nonstructural (ns) proteins were pathogenicity factors in mice, we identify both the ns1 and ns2 proteins as antagonists of alpha/beta interferon (ifn-a/ß) and ifn-? by use of recombinant pvm (rpvm) with single and combined deletions of the ns proteins (?ns1, ?ns2, and ? ...201121307191
a novel broad-spectrum treatment for respiratory virus infections: influenza-based defective interfering virus provides protection against pneumovirus infection in vivo.respiratory viruses represent a major clinical burden. few vaccines and antivirals are available, and the rapid appearance of resistant viruses is a cause for concern. we have developed a novel approach which exploits defective viruses (defective interfering (di) or protecting viruses). these are naturally occurring deletion mutants which are replication-deficient and multiply only when coinfection with a genetically compatible infectious virus provides missing function(s) in trans. interference ...201121320545
plasmacytoid dendritic cells promote host defense against acute pneumovirus infection via the tlr7-myd88-dependent signaling pathway.human respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infection in infants. in human infants, plasmacytoid dendritic cells (pdc) are recruited to the nasal compartment during infection and initiate host defense through the secretion of type i ifn, il-12, and il-6. however, rsv-infected pdc are refractory to tlr7-mediated activation. in this study, we used the rodent-specific pathogen, pneumonia virus of mice (pvm), to determine the contribution of pdc and tlr7 s ...201121482736
blocking induction of t helper type 2 responses prevents development of disease in a model of childhood asthma.early-life respiratory viral infections are linked to subsequent development of allergic asthma in children. we assessed the underlying immunological mechanisms in a novel model of the induction phase of childhood asthma. balb/c mice were infected neonatally with pneumonia virus of mice, then sensitized intranasally with ovalbumin following recovery. animals were challenged with low levels of aerosolized ovalbumin for 4 weeks to induce changes of chronic asthma, then received a single moderate-l ...201121501148
studies on pneumonia virus of mice (pvm) : iii. hemagglutination by the virus; the occurrence of combination between the virus and a tissue substance.1. the cause for the phenomenon of hemagglutination with heated pvm suspensions has been sought. 2. evidence in wide variety indicates that the component responsible for hemagglutination is the virus particle itself. 3. the virus is capable of combining with a substance present in lung tissue of certain mammalian host species susceptible to infection by pvm. the occurrence of such combination accounts for a number of unusual properties manifested by this pneumotropic virus.194619871517
centrifugation studies on pneumonia virus of mice (pvm) : the relative sizes of free and combined virus.a technique has been devised for obtaining free or uncombined pneumonia virus of mice (pvm). free pvm, liberated from infected mouse lungs by means of this technique, is infectious and causes hemagglutination directly. the results of quantitative studies carried out in the high speed angle centrifuge indicate that the free virus is relatively small, with dimensions of the order of 40 millimicrons. when it is in combination with lung tissue particles, pvm appears to be a relatively large virus wi ...194719871597
animal models of human respiratory syncytial virus disease.infection with the human pneumovirus pathogen, respiratory syncytial virus (hrsv), causes a wide spectrum of respiratory disease, notably among infants and the elderly. laboratory animal studies permit detailed experimental modeling of hrsv disease and are therefore indispensable in the search for novel therapies and preventative strategies. current animal models include several target species for hrsv, including chimpanzees, cattle, sheep, cotton rats and mice, as well as alternative animal pne ...201121571908
canine pneumovirus replicates in mouse lung tissue and elicits inflammatory pathology.canine pneumovirus (cnpnv) was recently isolated from the respiratory tracts of shelter dogs and shares sequence similarity with the rodent pathogen, pneumonia virus of mice (pvm). we show here that cnpnv replicates in and can elicit local proinflammatory cytokine production and neutrophil recruitment to lung tissue and the airways. in contrast to pvm j3666 infection, fatal cnpnv infections are observed only in response to high titer intranasal inocula (>67 tcid(50) units). sera from mice that r ...201121600624
role of the fas/fasl system in a model of rsv infection in mechanically ventilated mice.infection with respiratory syncytial virus (rsv) in children can progress to respiratory distress and acute lung injury (ali) necessitating mechanical ventilation (mv). mv enhances apoptosis and inflammation in mice infected with pneumonia virus of mice (pvm), a mouse pneumovirus that has been used as a model for severe rsv infection in mice. we hypothesized that the fas/fas ligand (fasl) system, a dual pro-apoptotic/pro-inflammatory system involved in other forms of lung injury, is required for ...201121743025
chemr23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia.viral diseases of the respiratory tract, which include influenza pandemic, children acute bronchiolitis, and viral pneumonia of the elderly, represent major health problems. plasmacytoid dendritic cells play an important role in anti-viral immunity, and these cells were recently shown to express chemr23, the receptor for the chemoattractant protein chemerin, which is expressed by epithelial cells in the lung. our aim was to determine the role played by the chemerin/chemr23 system in the physiopa ...201122072972
properties of pneumonia virus of mice (pvm) in relation to its state.additional evidence is presented that pvm is capable of combining firmly with lung tissue particles or erythrocytes from certain susceptible species. release of the virus from such combination can be effected by treatment with alkali as well as by heating. free virus expressed from infected lungs without grinding the tissues is infectious and causes hemagglutination when tested directly. the concentration of virus can be estimated more accurately by means of the hemagglutination technique than f ...194719871598
the pneumonia virus of mice (pvm) model of acute respiratory infection.pneumonia virus of mice (pvm) is related to the human and bovine respiratory syncytial virus (rsv) pathogens, and has been used to study respiratory virus replication and the ensuing inflammatory response as a component of a natural host—pathogen relationship. as such, pvm infection in mice reproduces many of the clinical and pathologic features of the more severe forms of rsv infection in human infants. here we review some of the most recent findings on the basic biology of pvm infection and it ...201223342367
lactobacillus priming of the respiratory tract: heterologous immunity and protection against lethal pneumovirus infection.we showed previously that wild-type mice primed via intranasal inoculation with live or heat-inactivated lactobacillus species were fully (100%) protected against the lethal sequelae of infection with the virulent pathogen, pneumonia virus of mice (pvm), a response that is associated with diminished expression of proinflammatory cytokines and diminished virus recovery. we show here that 40% of the mice primed with live lactobacillus survived when pvm challenge was delayed for 5months. this robus ...201223274789
priming of the respiratory tract with immunobiotic lactobacillus plantarum limits infection of alveolar macrophages with recombinant pneumonia virus of mice (rk2-pvm).pneumonia virus of mice (pvm) is a natural rodent pathogen that replicates in bronchial epithelial cells and reproduces many clinical and pathological features of the more severe forms of disease associated with human respiratory syncytial virus. in order to track virus-target cell interactions during acute infection in vivo, we developed rk2-pvm, bacterial artificial chromosome-based recombinant pvm strain j3666 that incorporates the fluorescent tag monomeric katushka 2 (mkate2). the rk2-pvm pa ...201526537680
activated mouse eosinophils protect against lethal respiratory virus infection.eosinophils are recruited to the airways as a prominent feature of the asthmatic inflammatory response where they are broadly perceived as promoting pathophysiology. respiratory virus infections exacerbate established asthma; however, the role of eosinophils and the nature of their interactions with respiratory viruses remain uncertain. to explore these questions, we established acute infection with the rodent pneumovirus, pneumonia virus of mice (pvm), in 3 distinct mouse models of th2 cytokine ...201424297871
animal models of respiratory syncytial virus infection.human respiratory syncytial virus (hrsv) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. there is no licensed hrsv vaccine or effective therapeutic agent. however, there are a growing number of hrsv vaccine candidates that have been developed targeting different populations at risk of hrsv infection. animal models of hrsv play an important role in the preclinical testi ...201727908639
cross-neutralization of four paramyxoviruses by a human monoclonal antibody.broadly neutralizing antibodies reactive against most and even all variants of the same viral species have been described for influenza and hiv-1 (ref. 1). however, whether a neutralizing antibody could have the breadth of range to target different viral species was unknown. human respiratory syncytial virus (hrsv) and human metapneumovirus (hmpv) are common pathogens that cause severe disease in premature newborns, hospitalized children and immune-compromised patients, and play a role in asthma ...201323955151
pre-existing virus-specific cd8(+) t-cells provide protection against pneumovirus-induced disease in mice.pneumoviruses such as pneumonia virus of mice (pvm), bovine respiratory syncytial virus (brsv) or human (h)rsv are closely related pneumoviruses that cause severe respiratory disease in their respective hosts. it is well-known that t-cell responses are essential in pneumovirus clearance, but pneumovirus-specific t-cell responses also are important mediators of severe immunopathology. in this study we determined whether memory- or pre-existing, transferred virus-specific cd8(+) t-cells provide pr ...201222940382
pneumovirus-induced lung disease in mice is independent of neutrophil-driven inflammation.the human pneumovirus respiratory syncytial virus (rsv) is the most common pathogen causing lower respiratory tract disease in young children worldwide. a hallmark of severe human rsv infection is the strong neutrophil recruitment to the airways and lungs. massive neutrophil activation has been proven detrimental in numerous diseases, yet in rsv the contribution of neutrophils to disease severity, and thereby, the relevance of targeting them, is largely unknown. to determine the relevance of pot ...201628005954
the caspase inhibitor zvad increases lung inflammation in pneumovirus infection in mice.severe respiratory syncytial virus (rsv) disease is a frequent cause of acute respiratory distress syndrome (ards) in young children, and is associated with marked lung epithelial injury and neutrophilic inflammation. experimental studies on ards have shown that inhibition of apoptosis in the lungs reduces lung epithelial injury. however, the blockade of apoptosis in the lungs may also have deleterious effects by hampering viral clearance, and importantly, by enhancing or prolonging local proinf ...201525780096
unique nonstructural proteins of pneumonia virus of mice (pvm) promote degradation of interferon (ifn) pathway components and ifn-stimulated gene proteins.pneumonia virus of mice (pvm) is the only virus that shares the pneumovirus genus of the paramyxoviridae family with respiratory syncytial virus (rsv). a deadly mouse pathogen, pvm has the potential to serve as a robust animal model of rsv infection, since human rsv does not fully replicate the human pathology in mice. like rsv, pvm also encodes two nonstructural proteins that have been implicated to suppress the ifn pathway, but surprisingly, they exhibit no sequence similarity with their rsv e ...201627905537
intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice.pneumonia virus of mice (pvm) infection of balb/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. this model system was used to investigate delivery of the internal structural proteins of pvm as a potential vaccination strategy to protect against pneumovirus disease. ...201526529077
the effect of tip on pneumovirus-induced pulmonary edema in mice.pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (rsv)-induced respiratory failure. in this study we determined whether treatment with tip (ap301), a synthetic cyclic peptide that mimics the lectin-like domain of human tnf, decreases pulmonary edema in a mouse model of severe human rsv infection. tip is currently undergoing clinical trials as a therapy for pulmonary permeability edema and has been shown to decrease pulmonary edema in different lung injur ...201425047452
animal model of respiratory syncytial virus: cd8+ t cells cause a cytokine storm that is chemically tractable by sphingosine-1-phosphate 1 receptor agonist therapy.the cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components. the cytokine storm during influenza virus infection, whereby the amplified innate immune response is primarily responsible for pulmonary damage, has been well characterized. now we describe a novel event where virus-specific t cells induce a cytokine storm. the paramyxovirus pneumonia virus of mice (pvm) is a model of human respiratory syncytial virus (hrsv). ...201424672024
cd8+ t-cell epitope mapping for pneumonia virus of mice in h-2b mice.the paramyxovirus pneumonia virus of mice (pvm) is a rodent model of human respiratory syncytial virus (hrsv) pathogenesis. here we characterized the pvm-specific cd8(+) t-cell repertoire in susceptible c57bl/6 mice. in total, 15 pvm-specific cd8(+) t-cell epitopes restricted by h-2d(b) and/or h-2k(b) were identified. these data open the door for using widely profiled, genetically manipulated c57bl/6 mice to study the contribution of epitope-specific cd8(+) t cells to pvm pathogenesis.201323824814
novel pneumoviruses (pnvs): evolution and inflammatory pathology.a previous report of a novel pneumovirus (pnv) isolated from the respiratory tract of a dog described its significant homology to the rodent pathogen, pneumonia virus of mice (pvm). the original pnv-ane4 pathogen replicated in and could be re-isolated in infectious state from mouse lung but elicited minimal mortality compared to pvm strain j3666. here we assess phylogeny and physiologic responses to 10 new pnv isolates. the g/glycoprotein sequences of all pnvs include elongated amino-termini whe ...201323763766
toll-like receptor 7 gene deficiency and early-life pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice.respiratory tract viruses are a major environmental risk factor for both the inception and exacerbations of asthma. genetic defects in toll-like receptor (tlr) 7-mediated signaling, impaired type i interferon responses, or both have been reported in asthmatic patients, although their contribution to the onset and exacerbation of asthma remains poorly understood.201323561801
evaluation of pneumonia virus of mice as a possible human pathogen.pneumonia virus of mice (pvm), a relative of human respiratory syncytial virus (rsv), causes respiratory disease in mice. there is serologic evidence suggesting widespread exposure of humans to pvm. to investigate replication in primates, african green monkeys (agm) and rhesus macaques (n = 4) were inoculated with pvm by the respiratory route. virus was shed intermittently at low levels by a subset of animals, suggesting poor permissiveness. pvm efficiently replicated in cultured human cells and ...201222438539
s. mansoni bolsters anti-viral immunity in the murine respiratory tract.the human intestinal parasite schistosoma mansoni causes a chronic disease, schistosomiasis or bilharzia. according to the current literature, the parasite induces vigorous immune responses that are controlled by th2 helper cells at the expense of th1 helper cells. the latter cell type is, however, indispensable for anti-viral immune responses. remarkably, there is no reliable literature among 230 million patients worldwide describing defective anti-viral immune responses in the upper respirator ...201425398130
immunobiotic lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.we reported previously that priming of the respiratory tract with immunobiotic lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (pvm). we present here the results of gene microarray which document differential expression of proinflammatory mediators in response to pvm infection alone and those suppressed in response to lactobacillus plantarum. we also demonstrate for the first time that intranasal inoculation with live or heat- ...201526145728
b cells are not essential for lactobacillus-mediated protection against lethal pneumovirus infection.we have shown previously that priming of respiratory mucosa with live lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. because b cells have been shown to p ...201424748495
characterisation of murine pneumonia virus proteins. 1979462813
persistent infection of bhk-21 cells with pneumonia virus of mice.trypsinization of bhk-21 cells 72 h after primary infection with pneumonia virus of mice yielded clones of persistently infected cells which specifically adsorbed murine erythrocytes. we describe one clone of cells, the progeny of which, after more than 100 passages, still bore viral antigen demonstrable by immunofluorescence and immune electron microscopy, but produced little or no detectable infectious virus.1978565825
immortalized mh-s cells lack defining features of primary alveolar macrophages and do not support mouse pneumovirus replication.the sv-40-transformed mh-s cell line maintains some, but not all, features of primary alveolar macrophages (ams) from balb/c mice. we show here that mh-s cells produce inflammatory cytokines il-6 and cxcl10 in response to challenge with gram-positive lactobacillus reuteri, and to tlr2 and nod2 ligands pam3csk4 and mdp, respectively. in contrast, although wild-type ams are infected in vivo by pneumonia virus of mice (pvm), no virus replication was detected in mh-s cells. interestingly, the surfac ...201626916143
epidemiological and phylogenetic analysis of institutional mouse parvoviruses.mouse parvoviruses (mpvs) are small, single-stranded, 5 kb dna viruses that are subclinical and endemic in many laboratory mouse colonies. mpvs cause more distinctive deleterious effects in immune-compromised or genetically-engineered mice than immuno-competent mice. at the university of louisville (u of l), there was an unexpected increase of mpv sero-positivity for mpv infections in mouse colonies between january 2006 and february 2007, resulting in strategic husbandry changes aimed at control ...201323545399
hygienic monitoring of mongolian gerbils: which mouse viruses should be included?the mongolian gerbil (meriones unguiculatus) serves as an animal model for a wide range of diseases. a practical limitation in its use is the definition of the hygienic status, as not much is known about viruses that potentially infect gerbils and might be transmitted to other rodents. as successful re-derivation was recently described for gerbils, we now aimed at investigating which mouse viruses induce seroconversion in gerbils and might be transmitted to mice. gerbils were inoculated with vir ...201222334874
prevalence of viral, bacterial and parasitological diseases in rats and mice used in research environments in australasia over a 5-y period.viral, bacterial and parasitological infections in rats and mice used in biomedical research continue to occur despite improved housing and biosurveillance. the presence of disease in laboratory animals can lead to spurious results for research undertaken in universities, research institutes and the pharmaceutical industry. here the authors report the results of serological, microbiological, parasitological and molecular tests done on mice and rats from australasia submitted to a rodent health m ...201122012194
Depletion of alveolar macrophages prolongs survival in response to acute pneumovirus infection.Alveolar macrophages are immunoregulatory effector cells that interact directly with respiratory virus pathogens in vivo. We examined the role of alveolar macrophages in acute infection with pneumonia virus of mice (PVM), a rodent pneumovirus that replicates the clinical sequelae of severe human respiratory syncytial virus disease. We show that PVM replicates in primary mouse macrophage culture, releasing infectious virions and proinflammatory cytokines. Alveolar macrophages isolated from PVM-in ...201222129848
il-21 promotes the pathologic immune response to pneumovirus infection.il-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of b cells, increased ig production, and the development of th17 and t follicular helper cells. il-21 is also implicated in the development of autoimmune disease and has antitumor activity. in this study, we investigated the role of il-21 in host defense to pneumonia virus of mice (pvm), which initiates an infection in mice resembling that of respiratory syncytial virus disease in humans. we found that pvm-infected ...201222238461
feral swine virome is dominated by single-stranded dna viruses and contains a novel orthopneumovirus which circulates both in feral and domestic swine.feral swine are known reservoirs for various pathogens that can adversely affect domestic animals. to assess the viral ecology of feral swine in the usa, metagenomic sequencing was performed on 100 pooled nasal swabs. the virome was dominated by small, ssdna viruses belonging to the families circoviridae, anelloviridae and parvovirinae. only four rna viruses were identified: porcine kobuvirus, porcine sapelovirus, atypical porcine pestivirus and a novel orthopneumovirus, provisionally named swin ...201627417702
il-12p40 gene-deficient balb/c mice exhibit lower weight loss, reduced lung pathology and decreased sensitization to allergen in response to infection with pneumonia virus of mice.respiratory syncytial virus (rsv) is a major cause of bronchiolitis and pneumonia in infants and pneumonia virus of mice (pvm) causes similar disease. balb/c mice are highly susceptible, while c57bl/6 mice are more resistant to pvm. il-12 was significantly more up-regulated in response to pvm infection in balb/c than in c57bl/6 mice. il-12p40-deficient neonatal and adult balb/c mice showed significantly less weight loss than wild-type mice after pvm challenge. the percentage of regulatory t cell ...201627400340
aeroallergen-induced il-33 predisposes to respiratory virus-induced asthma by dampening antiviral immunity.frequent viral lower respiratory infections in early life are an independent risk factor for asthma onset. this risk and the development of persistent asthma are significantly greater in children who later become sensitized.201627236500
timing of cd8 t cell effector responses in viral infections.cd8 t cell or cytotoxic t lymphocyte (ctl) responses are an important branch of the immune system in the fight against viral infections. the dynamics of anti-viral ctl responses have been characterized in some detail, both experimentally and with mathematical models. an interesting experimental observation concerns the timing of ctl responses. a recent study reported that in pneumonia virus of mice the effector ctl tended to arrive in the lung only after maximal virus loads had been achieved, an ...201626998338
the response of aged mice to primary infection and re-infection with pneumonia virus of mice depends on their genetic background.the pneumonia virus of mice (pvm) model is used to study respiratory syncytial virus (rsv) pathogenesis. the outcome of pvm infection varies in different inbred mouse strains, balb/c being highly susceptible and c57bl/6 more resistant. as the disease symptoms induced by rsv infection can become more severe as people age, we examined the primary and secondary immune responses to infection with pvm in aged balb/c and c57bl/6 mice. based on clinical parameters, aged c57bl/6 mice displayed less seve ...201626621546
blunted inflammatory and mucosal iga responses to pneumonia virus of mice in c57bl/6 neonates are correlated to reduced protective immunity upon re-infection as elderly mice.respiratory syncytial virus is a major cause of bronchiolitis in infants and pneumonia virus of mice (pvm) causes similar disease in mice. the impact of pvm infection in balb/c and c57bl/6 neonates, and upon re-infection as elderly mice, was compared. as previously shown for adult mice, pvm caused more disease in balb/c than in c57bl/6 neonates. after pvm-15 infection balb/c neonates showed higher production of inflammatory mediators, more influx of plasmacytoid dendritic cells and higher ifn-α ...201526298860
il-21-mediated non-canonical pathway for il-1β production in conventional dendritic cells.the canonical pathway for il-1β production requires tlr-mediated nf-κb-dependent il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-il-1β. here we show that il-21 unexpectedly induces il-1β production in conventional dendritic cells (cdcs) via a stat3-dependent but nf-κb-independent pathway. il-21 does not induce il1b expression in cd4(+) t cells, with differential histone marks present in these cells versus cdcs. il-21-induced il-1β processing in cdcs do ...201526269257
sustained inflammation and differential expression of interferons type i and iii in pvm-infected interferon-gamma (ifnγ) gene-deleted mice.interferon gamma (ifnγ) has complex immunomodulatory and antiviral properties. while ifnγ is detected in the airways in response to infection with the pneumovirus pathogen, pneumonia virus of mice (pvm; family paramyxoviridae), its role in promoting disease has not been fully explored. here, we evaluate pvm infection in ifnγ(-/-) mice. although the ifnγ gene-deletion has no impact on weight loss, survival or virus kinetics, expression of ifnβ, ifnλ2/3 and ifn-stimulated 2-5' oligoadenylate synth ...201425173090
detection of a pneumonia virus of mice (pvm) in an african hedgehog (atelerix arbiventris) with suspected wobbly hedgehog syndrome (whs).a pneumonia virus of mice (pvm) from an african hedgehog (atelerix arbiventris) with suspected wobbly hedgehog syndrome (whs) was detected and genetically characterized. the affected hedgehog had a nonsuppurative encephalitis with vacuolization of the white matter, and the brain samples yielded rna reads highly homogeneous to pvm strain 15 (96.5% of full genomic sequence homology by analysis of next generation sequencing). pvm antigen was also detected in the brain and the lungs immunohistochemi ...201425129384
eosinophils and respiratory virus infection: a dual-standard curve qrt-pcr-based method for determining virus recovery from mouse lung tissue.several lines of investigation have indicated a role for eosinophilic leukocytes in limiting virus infectivity and promoting virion clearance. we have established a respiratory virus infection model with pneumonia virus of mice (pvm; family paramyxoviridae), a natural mouse pathogen that replicates the more severe forms of human disease elicited by the phylogenetically related respiratory syncytial virus (rsv). in this chapter, we present a rapid and highly reproducible dual-standard curve qrt-p ...201424986623
in situ evolution of virus-specific cytotoxic t cell responses in the lung.cytotoxic t cells (ctl) play a critical role in the clearance of respiratory viral infections, but they also contribute to disease manifestations. in this study, we infected mice with a genetically modified pneumonia virus of mice (pvm) that allowed visualization of virus-specific ctl and infected cells in situ. the first virus-specific t cells entered the lung via blood vessels in the scattered foci of pvm-infected cells, which densely clustered around the bronchi at day 7 after infection. at t ...201323946463
cardiac dysfunction in pneumovirus-induced lung injury in mice.to determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice.201323867445
innate and adaptive immune response to pneumonia virus of mice in a resistant and a susceptible mouse strain.respiratory syncytial virus (rsv) is the leading cause of infant bronchiolitis. the closely related pneumonia virus of mice (pvm) causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. this project was designed to compare the immune responses to lethal and sublethal doses of pvm strain 15 in balb/c and c57bl/6 mice. balb/c mice responded to pvm infection with an earlier and stronger innate response that failed to control viral repl ...201323337382
protective role of p2y2 receptor against lung infection induced by pneumonia virus of mice.atp released in the early inflammatory processes acts as a danger signal by binding to purinergic receptors expressed on immune cells. a major contribution of the p2y(2) receptor of atp/utp to dendritic cell function and th2 lymphocyte recruitment during asthmatic airway inflammation was previously reported. we investigated here the involvement of p2y(2) receptor in lung inflammation initiated by pneumonia virus of mice infection. we demonstrated that p2y(2) (-/-) mice display a severe increase ...201223185614
characterization of the resistance of sjl/j mice to pneumonia virus of mice, a model for infantile bronchiolitis due to a respiratory syncytial virus.respiratory syncytial virus (rsv), a prominent cause of airway morbidity in children, maintains an excessive hospitalization rate despite decades of research. host factors are assumed to influence the disease severity. as a first step toward identifying the underlying resistance mechanisms, we recently showed that inbred mouse strains differ dramatically as regards their susceptibility to pneumonia virus of mice (pvm), the murine counterpart of rsv. pvm infection in mice has been shown to faithf ...201223077483
in vivo modulation of the innate response to pneumovirus by type-i and -iii interferon-induced bos taurus mx1.the respiratory syncytial virus (rsv) is a major pathogen of the human species. this pneumovirus is a prominent cause of airway morbidity in children and maintains an excessive hospitalization rate despite decades of research. as involvement of a genetic vulnerability is a possibility supported by recent data, we addressed the question of whether the mx gene products, the typical target of which consists in single-stranded negative-polarity rna viruses, could alter the course of pneumovirus-asso ...201222385204
plaque assay for pneumonia virus of mice.a plaque assay for the quantitation of pneumonia virus of mice is described. to obtain reproducible plaque formation, proteolytic enzymes had to be incorporated in the overlay medium. the plaque morphology observed in the presence of pancreatin and chymotrypsin was superior to that seen with trypsin. although the plaque assay was found to be slightly less sensitive than the tcid(50) determination described by harter and choppin, it enables cloning of the virus by plaque selection and permits fur ...19705530275
a comparison of some properties of polyoma virus and pneumonia virus of mice. 196113894685
epitope mapping and kinetics of cd4 t cell immunity to pneumonia virus of mice in the c57bl/6 strain.pneumonia virus of mice (pvm) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hrsv). while t cells are indispensable for viral clearance, they also contribute to immunopathology. to gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific t cells in c57bl/6 mice as the majority of transgenic mice are only available on this background. while pvm-specific cd8 t cell epitopes were recently ...201728615708
the absence of interferon-β promotor stimulator-1 (ips-1) predisposes to bronchiolitis and asthma-like pathology in response to pneumoviral infection in mice.respiratory syncytial virus (rsv)-bronchiolitis is a major cause of infant morbidity and mortality and a risk factor for subsequent asthma. we showed previously that toll-like receptor (tlr)7 in plasmacytoid dendritic cells (pdcs) is critical for protection against bronchiolitis and asthma in mice infected with pneumonia virus of mice (pvm), the mouse homolog of rsv. this lack of redundancy was unexpected as interferon-β promotor stimulator-1 (ips-1) signalling, downstream of rig-i-like receptor ...201728539639
rage deficiency predisposes mice to virus-induced paucigranulocytic asthma.asthma is a chronic inflammatory disease. although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. the aetiology of paucigranulocytic asthma is unknown. however, both respiratory syncytial virus (rsv) infection and mutations in the receptor for advanced glycation endproducts (rage) are risk factors for asthma development. here, we show that rage def ...201728099113
intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice.respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract infections in infants and young children. there are no licensed rsv vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. immunomodulation mediated by a novel formulation consisting of the toll-like receptor 3 agonist poly(i:c), an innate defense regulator peptide and a polyphosphazene (p-i-p) was evaluated in the con ...201627771388
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