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host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
molecular epidemiology of human respiratory syncytial virus subgroups a and b identified in adults with hematological malignancy attending an irish hospital between 2004 and 2009.human respiratory syncytial virus (hrsv) is an important cause of respiratory infection in patients with hematological malignancy, particularly hematopoietic stem cell transplant recipients. this study investigated the genetic variability of the attachment (g) protein gene among hrsv isolates collected from adult patients with hematological malignancy. between december 2004 and march 2009, 60 samples collected from 58 adults attending an irish hospital were positive for hrsv by direct immunofluo ...201121181932
myocarditis in the setting of rsv bronchiolitis.myocarditis in the pediatric population is commonly caused by viral pathogens, notably entero virus and adeno virus. respiratory syncytial virus, although widespread among this population, is rarely associated with myocarditis. the incidence of myocarditis is unknown due to the variability of clinical presentation and diagnostic limitations. data regarding prognosis is lacking in children. patients should be monitored in a pediatric intensive care unit secondary to the risk of hemodynamic compro ...201121204669
the cellular endosomal sorting complex required for transport pathway is not involved in avian metapneumovirus budding in a virus-like-particle expression system.avian metapneumovirus (ampv) is a paramyxovirus that principally causes respiratory disease and egg production drops in turkeys and chickens. together with its closely related human metapneumovirus (hmpv), they comprise the genus metapneumovirus in the family paramyxoviridae. little is currently known about the mechanisms involved in the budding of metapneumovirus. by using ampv as a model system, we showed that the matrix (m) protein by itself was insufficient to form virus-like-particles (vlps ...201121248175
differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells.human respiratory syncytial virus (rsv) causes severe respiratory disease in infants. airway epithelial cells are the principle targets of rsv infection. however, the mechanisms by which it causes disease are poorly understood. most rsv pathogenesis data are derived using laboratory-adapted prototypic strains. we hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (pbecs).201121272337
soluble respiratory syncytial virus fusion protein in the fully cleaved, pretriggered state is triggered by exposure to low-molarity buffer.the paramyxovirus fusion (f) glycoprotein is anchored in the virion membrane in a metastable, pretriggered form. once triggered, the f protein undergoes a dramatic conformational extension that inserts its hydrophobic fusion peptide into the target cell membrane, then folds back on itself to bring the membranes together and initiate fusion. unlike most other paramyxoviruses, the respiratory syncytial virus (rsv) f protein alone is sufficient to mediate membrane fusion and virus infection. to stu ...201121307202
large-scale seroprevalence analysis of human metapneumovirus and human respiratory syncytial virus infections in beijing, china.human metapneumovirus (hmpv), a recently identified virus, causes acute respiratory tract infections (artis) in infants and children. however, studies on the seroepidemeology of hmpv are very limited in china. to assess the seroprevalence of hmpv infection in china, we tested a total of 1,156 serum specimens for the presence of anti-hmpv igg antibody in children and adults free of acute respiratory illness in beijing, china by using hmpv nucleocapsid (n) protein as an antigen. as a control, we u ...201121310026
a novel capillary electrophoresis-based multiplex pcr assay for detection of respiratory pathogens.the field of infectious disease testing has recently experienced rapid expansion in the number of multiplexed pcr-based assays available for detecting respiratory pathogens. this study provides a preliminary evaluation of a multiplex assay from seegene that uses capillary electrophoresis as the detection platform for viral and bacterial respiratory pathogens. we compared this technology to a real-time pcr assay for 3 viral targets. thirty respiratory samples were collected that had previously te ...201121325252
use of palivizumab and infection control measures to control an outbreak of respiratory syncytial virus in a neonatal intensive care unit confirmed by real-time polymerase chain reaction.respiratory syncytial virus (rsv) is a potentially life-threatening infection in premature infants. we report an outbreak involving four infants in the neonatal intensive care unit (nicu) of our hospital that occurred in february 2010. rsv a infection was confirmed by real-time polymerase chain reaction. palivizumab was administered to all infants in the nicu. there were no additional symptomatic cases and repeat rsv surveillance confirmed that there was no further cross-transmission within the ...201121330007
dexamethasone in children mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus: a randomized controlled trial.to determine the efficacy of dexamethasone in the treatment of mechanically ventilated children with respiratory syncytial virus-severe lower respiratory tract infection.201121460709
acute lower respiratory tract infection due to respiratory syncytial virus in a group of egyptian children under 5 years of age.respiratory syncytial virus (rsv) is one of the most important causes of acute lower respiratory tract infections (alrti) in infants and young children. this study was conducted to describe the epidemiology of alrti associated with rsv among children = 5 years old in egypt.201121466713
modeling the variations in pediatric respiratory syncytial virus seasonal epidemics.abstract:201121510889
detection of ki polyomavirus and wu polyomavirus dna by real-time pcr in nasopharyngeal swabs and in normal lung and lung adenocarcinoma tissues.polyomaviruses ki (kipyv) and wu (wupyv) were detected from 7 (3.0%) and 38 (16.4%) of 232 children with respiratory tract infections by real-time pcr. the rates of single infection of kipyv and wupyv were 3 (42.9%) of 7 and 20 (52.6%) of 38, respectively. in other samples, various viruses (human respiratory syncytial virus, human metapneumovirus (hmpv), human rhinovirus, parainfluenza virus 1 and human bocavirus) were detected simultaneously. one case was positive for kipyv and wupyv and also f ...201121545509
inhibition of respiratory syncytial virus in vitro and in vivo by the immunosuppressive agent leflunomide.respiratory syncytial virus (rsv) is the primary cause of bronchiolitis and pneumonia in infants and young children worldwide and is often the cause of infections in bone marrow, solid organ transplant, cystic fibrosis and congenital heart disease patients, as well as respiratory tract disease in elderly adults. treatment options are limited to ribavirin, which is only marginally effective, and passive immunoprophylaxis, which is very expensive. the immunosuppressive agent leflunomide has been s ...201121555813
relationship between rantes polymorphisms and respiratory syncytial virus bronchiolitis in a japanese infant population.respiratory syncytial virus (rsv) is the most important virus associated with bronchiolitis in infants and young children. the regulated upon activation, normal t-cell expressed and secreted protein (rantes, also known as ccl5) appears to be a key player in the etiology of rsv-infected airway inflammation. in this study, we genotyped three single-nucleotide polymorphisms in the rantes gene: -403g/a, -28c/g, and in1.1t/c in 59 infants with severe rsv bronchiolitis and 201 control subjects. the fr ...201121617311
a novel mechanism for inhibition of irf-3-dependent gene expression by human respiratory syncytial virus ns1 protein.human respiratory syncytial virus (rsv), a leading cause of respiratory tract infections in infants, inhibits type i interferon (ifn)-dependent signaling, as well as ifn synthesis. rsv nonstructural protein ns1 plays a significant role in this inhibition, however the mechanism(s) responsible are not fully known. the transcription factor interferon regulatory factor (irf)-3 is essential for viral-induced ifn-α synthesis. in this study, we found that ns1 protein inhibits irf-3-dependent gene trans ...201121632562
whole genome characterization of non-tissue culture adapted hrsv strains in severely infected children.abstract: background: human respiratory syncytial virus (hrsv) is the most important virus causing lower respiratory infection in young children. the complete genetic characterization of rsv clinical strains is a prerequisite for understanding hrsv infection in the clinical context. current information about the genetic structure of the hrsv genome has largely been obtained using tissue culture adapted viruses. during tissue culture adaptation genetic changes can be introduced into the virus gen ...201121794174
Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice.Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral death in infants. Despite decades of research with traditional or subunit vaccine approaches, there are no approved RSV vaccines. New approaches are therefore urgently needed to develop effective RSV vaccines.201121881112
activation of toll-like receptor 9 and production of epitope specific antibody by liposome-encapsulated cpg-dna.several investigators have shown that cpg-dna has outstanding effects as a th1-responsive adjuvant and that its potent adjuvant effects are enhanced by encapsulation with a liposome of proper composition. in this study, we showed that encapsulation with phosphatidyl-β-oleoyl-γ-palmitoyl ethanolamine (dope): cholesterol hemisuccinate (chems) complex enhances the immunostimulatory activity of cpg dna and the binding of cpg-dna to tlr9. we also examined involvement of myeloid differentiation protei ...201121944255
disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (daly) model.the most common acute infections occur in the respiratory tract. recent discoveries of several novel viruses have markedly increased the repertoire of agents understood to cause presentations of acute respiratory disease.201121880543
The respiratory syncytial virus transcription antiterminator M(2-1) is a highly stable, zinc binding tetramer with strong pH-dependent dissociation and a monomeric unfolding intermediate.The human respiratory syncytial virus M(2-1) transcription antiterminator is an essential elongation factor required by the RNA polymerase for effective transcription beyond the first two nonstructural genes. Its exclusive presence in pneumovirus among all paramyxovirus suggests a unique function within this small genus. With the aim of understanding its biochemical properties, we investigated this a-helical tetramer by making use of a biophysical approach. We found that the tetramer hydrodynami ...201121877705
whole genome sequencing and evolutionary analysis of human respiratory syncytial virus a and b from milwaukee, wi 1998-2010.respiratory syncytial virus (rsv) is the leading cause of lower respiratory-tract infections in infants and young children worldwide. despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for rsv group a and group b respectively.201121998661
the prophylaxis and treatment with antiviral agents of respiratory syncytial virus infections.in this review, we consider recent advances in the discovery and development of antiviral agents for respiratory syncytial virus (rsv) infections. a background to the various manifestations of human rsv infection and current treatments is provided. the technical, clinical and commercial issues surrounding the development of such antiviral agents are discussed.201122182737
different cytokine profile and eosinophil activation are involved in rhinovirus- and rs virus-induced acute exacerbation of childhood wheezing.because little information is available on eosinophil activation and cytokine response in virus-induced wheezing, we attempted to detect respiratory viruses and measure eosinophil cationic protein (ecp), and 27 types of cytokines/chemokines in both serum and nasal secretions from children with wheezing. this study was an observational, case-control investigation of 267 subjects, who were visited and/or hospitalized with acute respiratory symptoms (with wheezing: men, 115; women, 59; mean/median ...201120408969
serum antibody response to respiratory syncytial virus f and n proteins in two populations at high risk of infection: children and elderly.human respiratory syncytial virus (hrsv) is the main viral cause of severe respiratory infections in children and a common cause of morbidity in the elderly. the nucleocapsid (n) and fusion (f) proteins of hrsv were expressed in insect cells and used as antigens in two independent enzyme-linked immunosorbent assays (elisas) to measure the serum antibody response in two populations at high risk of hrsv infection, children and the elderly. fifty-seven serum specimens from children aged from 1 to 1 ...201020488207
ten years of global evolution of the human respiratory syncytial virus ba genotype with a 60-nucleotide duplication in the g protein gene.the emergence of natural isolates of human respiratory syncytial virus group b (hrsv-b) with a 60-nucleotide (nt) duplication in the g protein gene in buenos aires, argentina, in 1999 (a. trento et al., j. gen. virol. 84:3115-3120, 2003) and their dissemination worldwide allowed us to use the duplicated segment as a natural tag to examine in detail the evolution of hrsv during propagation in its natural host. viruses with the duplicated segment were all clustered in a new genotype, named ba (a. ...201020504933
viral respiratory infections in hospitalized and community control children in alaska.respiratory syncytial virus (rsv) in alaska native children from the yukon kuskokwim (yk) delta is associated with a hospitalization rate five times higher than that reported for the general us child population. the role of other viral respiratory pathogens has not been studied in this population. yk delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between october 2005 and september 2007. polymerase chain ...201020513097
neutralization of human respiratory syncytial virus infectivity by antibodies and low-molecular-weight compounds targeted against the fusion glycoprotein.human respiratory syncytial virus (hrsv) fusion (f) protein is an essential component of the virus envelope that mediates fusion of the viral and cell membranes, and, therefore, it is an attractive target for drug and vaccine development. our aim was to analyze the neutralizing mechanism of anti-f antibodies in comparison with other low-molecular-weight compounds targeted against the f molecule. it was found that neutralization by anti-f antibodies is related to epitope specificity. thus, neutra ...201020534864
[bronchiolitis viruses].in normandy (france), human respiratory syncytial virus (hrsv) was detected in 64.1% of acute bronchiolitis in hospitalized children, rhinovirus in 26.8%, human metapneumovirus (hmpv) in 7.6%, and parainfluenza virus (piv) in 3.4%. the viruses causing acute bronchiolitis in the community were hrsv (42%), rhinovirus (19.5%), coronavirus (8%), piv (3.5%), and hmpv (2.5%). in 53.7% of the cases, hrsv infected infants (86.9%), 53.7% being less than 6 months of age. of the hrsv cases, 48.2% were dete ...201020558050
virologically confirmed population-based burden of hospitalization caused by respiratory syncytial virus, adenovirus, and parainfluenza viruses in children in hong kong.to determine virologically confirmed hospitalization rates associated with respiratory syncytial virus (rsv), adenovirus, and parainfluenza viruses in hong kong children.201020622713
fosfomycin suppresses rs-virus-induced streptococcus pneumoniae and haemophilus influenzae adhesion to respiratory epithelial cells via the platelet-activating factor receptor.human respiratory syncytial virus (rsv) sometimes causes acute and severe lower respiratory tract illness in infants and young children. the platelet-activating factor (paf) receptor, which is a receptor for streptococcus pneumoniae and haemophilus influenzae, is upregulated by rsv infection in the pulmonary epithelial cell line a549. fosfomycin, an antimicrobial agent, significantly suppressed paf receptor induction by rsv infection at the mrna and cell surface expression levels. fosfomycin als ...201020629755
molecular quantification of respiratory syncytial virus in respiratory samples: reliable detection during the initial phase of infection.quantitative real-time pcr for the detection of respiratory syncytial virus (rsv) rna is increasingly used to study the causal role of rsv in lower airway disease. the objective of our study was to evaluate variations in rsv rna loads at different steps in the rna quantification process: (i) variation in rsv rna load within one sample (step 1), (ii) variation in the load in samples from patients who were sampled twice on the same day (step 2), and (iii) variation in the load between simultaneous ...201020660210
report of the 2nd "french clinical vaccinology meeting jean-gerard guillet": immunization and respiratory diseases.the 2nd french clinical vaccinology conference held on 20th april 2009 in paris (france) was a unique opportunity to discuss basic and translational research in vaccinology and its implications for patients for respiratory diseases. this conference is organized by the clinical research center cochin-pasteur, that has been involved for several years clinical research in vaccines. we report on here the key findings of the conference, especially the immunization of the chronic respiratory diseases, ...201020674881
respiratory morbidity in adulthood after respiratory syncytial virus hospitalization in infancy.a prospective >25-year follow-up study evaluated the outcome of patients hospitalized for respiratory syncytial virus (rsv) infection at <24 months of age. questionnaires were sent to 51 study subjects and to population controls. self-reported asthma was present in 30% of the former rsv patients, compared with 3.8% of controls. in adjusted analyses, rsv hospitalization was an independent risk factor of adulthood asthma.201020803817
nationwide survey of severe respiratory syncytial virus infection in children who do not meet indications for palivizumab in japan.in japan, palivizumab, a humanized monoclonal antibody specific for respiratory syncytial virus (rsv), has been available since 2002. however, its use is limited to children at risk of severe rsv infection, with specific criteria that have been validated in large-scale clinical studies. the pharmaceutical committee of the japan pediatric society established a committee to conduct a nationwide questionnaire survey to determine which diseases place children at risk of severe rsv infection and requ ...201020872156
immunohistochemical assessment of respiratory viruses in necropsy samples from lethal non-pandemic seasonal respiratory infections.acute respiratory infections are an important cause of childhood morbidity and mortality throughout the world, and viruses have often been reported to be an aetiological agent. this study aimed to identify respiratory viruses in paraffin-embedded samples of paediatric lung necropsy specimens, using immunohistochemistry on tissue microarray slides.201020876328
pulmonary infection of mice with human metapneumovirus induces local cytotoxic t-cell and immunoregulatory cytokine responses similar to those seen with human respiratory syncytial virus.human metapneumovirus (hmpv) is a major cause of upper and lower respiratory-tract infection in infants, the elderly and immunocompromised individuals. virus-directed cellular immunity elicited by hmpv infection is poorly understood, in contrast to the phylogenetically and clinically related pathogen human respiratory syncytial virus (hrsv). in a murine model of acute lower respiratory-tract infection with hmpv, we demonstrate the accumulation of gamma interferon (ifn-gamma)-producing cd8+ t cel ...201020053825
decreased replication of human respiratory syncytial virus treated with the proteasome inhibitor mg-132.many enveloped viruses require components of the host protein ubiquitin system including members of the paramyxoviridae family of viruses (piv5, sev). until recently, little has been known about the requirements of the subfamily pneumovirinae. we report here that treatment of vero cells with the proteasome inhibitor mg-132 results in the reduction of human respiratory syncytial virus (hrsv) titers by as much as 2.2log(10). inhibition of hrsv by mg-132 was only observed early in infection (4-14h ...201020080137
multiple, non-conserved, internal viral ligands naturally presented by hla-b27 in human respiratory syncytial virus-infected cells.cytotoxic t lymphocyte (ctl)-mediated death of virus-infected cells requires prior recognition of short viral peptide antigens that are presented by human leukocyte antigen (hla) class i molecules on the surface of infected cells. the ctl response is critical for the clearance of human respiratory syncytial virus (hrsv) infection. using mass spectrometry analysis of complex hla-bound peptide pools isolated from large amounts of hrsv-infected cells, we identified nine naturally processed hla-b27 ...201020081153
structural basis of respiratory syncytial virus neutralization by motavizumab.motavizumab is approximately tenfold more potent than its predecessor, palivizumab (synagis), the fda-approved monoclonal antibody used to prevent respiratory syncytial virus (rsv) infection. the structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the rsv fusion (f) glycoprotein reveals the structural basis for this greater potency. modeling suggests that motavizumab recognizes a different quaternary configuration of the f glycoprotein than that observed ...201020098425
single molecule sensitive multivalent polyethylene glycol probes for rna imaging.the imaging of rna in live cells presents a methodological challenge both in the mechanism by which the probes are delivered to the cell and in the sensitivity of the probe. probes must be delivered to the correct cellular compartment and, once inside the cell, should bind to the target rna rapidly and with enough sensitivity to detect small numbers of rna molecules. here, we report the characterization of a single-molecule sensitive, multivalent rna imaging probe that utilizes an eight-armed po ...201020141184
identification of and human serum reactogenicity to neutralizing epitopes within the central unglycosylated region of the respiratory syncytial virus attachment protein.we identified two overlapping neutralizing epitopes within residues 151 to 172 of the central unglycosylated region of the respiratory syncytial virus (rsv) attachment protein. in approximately 40% of hospitalized and outpatient adults infected with rsv subtype a, these contiguous residues are the target of > or =4-fold increases in igg response between acute- and convalescent-phase sera.201020164253
down syndrome and respiratory syncytial virus infection.we reviewed the medical records of all children with down syndrome (ds), hospitalized in our medical center due to infection with respiratory syncytial virus. during the 9-year study period, there were 41 hospitalizations of 39 children with ds. mean age was 1.3 years; mean duration of hospitalization was 10.9 days. patients with ds were older than healthy controls with respiratory syncytial virus infection and needed longer hospitalization.201020228692
a new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus.human and bovine respiratory syncytial viruses (hrsv and brsv) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. we reported that nasal vaccination with the hrsv nucleoprotein produced as recombinant ring-shaped nanoparticles (n(srs)) protects mice against a viral challenge with hrsv. the aim of this work was t ...201020307593
potential role of soluble trail in epithelial injury in children with severe rsv infection.lower respiratory tract infection by respiratory syncytial virus (rsv) is a frequent cause of acute lung injury in young children and infants. studies in adults and animals suggest that tumor necrosis factor receptor (tnfr) ligands may mediate lung injury by causing apoptosis of epithelial cells. the main goal of the present study was to determine whether the tnf-related apoptosis-inducing ligand (apo2l/trail) pathway may be implicated in epithelial injury during severe rsv infection in children ...201019635930
vaccination to induce antibodies blocking the cx3c-cx3cr1 interaction of respiratory syncytial virus g protein reduces pulmonary inflammation and virus replication in mice.respiratory syncytial virus (rsv) infection causes substantial morbidity and some deaths in the young and elderly worldwide. there is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-rsv antibody prophylaxis. rsv has been shown to modify the immune response to infection, a feature linked in part to rsv g protein cx3c chemokine mimicry. this study determined if vaccination with g protein polypeptides or peptides spa ...201019864390
treatment of human respiratory syncytial virus infected balb/c mice with the proteasome inhibitor bortezomib (velcade, ps-341) results in increased inflammation and mortality.human respiratory syncytial virus (hrsv) is an important pathogen and is associated with mortality in the young, old, and immuno-compromised. due to the lack of effective therapeutic antivirals or a vaccine, there is a critical need for continued research in this field. here we tested the ability of the fda approved proteasome inhibitor bortezomib to inhibit hrsv in vitro and in vivo. we observed significant inhibition of hrsv replication in vero cells at bortezomib concentrations from 20 to 40 ...201019931343
binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the rsv fusion protein.six-helix bundle (6hb) formation is an essential step for many viruses that rely on a class i fusion protein to enter a target cell and initiate replication. because the binding modes of small molecule inhibitors of 6hb formation are largely unknown, precisely how they disrupt 6hb formation remains unclear, and structure-based design of improved inhibitors is thus seriously hampered. here we present the high resolution crystal structure of tmc353121, a potent inhibitor of respiratory syncytial v ...201019966279
population based external validation of a european predictive model for respiratory syncytial virus hospitalization of premature infants born 33 to 35 weeks of gestational age.prospectively collected population-based data on 2529 danish infants born at 33 to 35 weeks of gestation were used to validate an european predictive model of respiratory syncytial virus (rsv) hospitalization. the model was found to be robust with a diagnostic accuracy of 65.9% to distinguish between rsv-hospitalized versus non-rsv-hospitalized danish infants born at 33 to 35 weeks of gestation.201020016397
streptococcus pneumoniae coinfection is correlated with the severity of h1n1 pandemic influenza.initial reports in may 2009 of the novel influenza strain h1n1pdm estimated a case fatality rate (cfr) of 0.6%, similar to that of seasonal influenza. in july 2009, however, argentina reported 3056 cases with 137 deaths, representing a cfr of 4.5%. potential explanations for increased cfr included virus reassortment or genetic drift, or infection of a more vulnerable population. virus genomic sequencing of 26 argentinian samples representing both severe and mild disease indicated no evidence of ...200920046873
[not only rsv can cause bronchiolitis in small children. human metapneumovirus maybe the the second most common cause]. 200919998817
human respiratory syncytial virus reduces the number of cells in s-phase and increases gadd153 expression in hep-2 cells.human respiratory syncytial virus (hrsv) associated with bronchiolitis and asthma is known to replicate actively in ciliated epithelial cells. however, little is known about the influence of hrsv replication on the cell cycle. we found that hrsv infection of hep-2 cells led to a reduction of the number of cells in s-phase, to an increase in the number of cells in g1-phase, together with an increase of gadd153 mrna levels and gadd153 protein expression. these results implied that a shorter s-phas ...200919953728
novel therapies for an old virus: treatment of rsv infections in the 21st century.respiratory syncytial virus (rsv) is a pathogen whose existence has been known for decades, causing mild-to-severe upper and lower respiratory tract infections that bear the risk of subsequent asthma and can even lead to a fatal outcome. rsv infects all groups of patients and is a major cause of hospitalization in children and in the elderly. this review briefly summarizes the current status of rsv drug development and clinical trials for drugs available for the treatment of rsv infections.200919883332
codon stabilization analysis of the "248" temperature sensitive mutation for increased phenotypic stability of respiratory syncytial virus vaccine candidates.human respiratory syncytial virus (rsv) is the most important viral agent of serious pediatric respiratory tract illness worldwide. presently, the most promising vaccine candidate is a live, attenuated, cdna-derived virus, rsv ra2cp248/404/1030deltash, whose attenuation phenotype is based in large part on a series of point mutations including a glutamine to leucine (q to l) substitution at amino acid residue 831 of the polymerase protein l, a mutation originally called "248". this mutation speci ...200919646406
respiratory syncytial virus infection induces a reactive oxygen species-msk1-phospho-ser-276 rela pathway required for cytokine expression.respiratory syncytial virus (rsv) is a human pathogen that induces airway inflammation, at least in part, by modulating gene expression programs in airway epithelial cells. the presence of rsv replication is detected by the intracellular retinoic acid-inducible gene i (rig-i) rna helicase that forms a productive signaling complex with the mitochondrion-anchored mavs protein, resulting in nuclear translocation of the nf-kappab transcription factor. although nuclear translocation is a prerequisite ...200919706715
mutational analysis reveals a noncontractile but interactive role of actin and profilin in viral rna-dependent rna synthesis.as obligatory parasites, viruses co-opt a variety of cellular functions for robust replication. the expression of the nonsegmented negative-strand rna genome of respiratory syncytial virus (rsv), a significant pediatric pathogen, absolutely requires actin and is stimulated by the actin-regulatory protein profilin. as actin is a major contractile protein, it was important to determine whether the known functional domains of actin and profilin were important for their ability to activate rsv trans ...200919710142
development of a real-time multiplex rsv detection assay for difficult respiratory samples, using ultrasone waves and mnazyme technology.elderly infected with human respiratory syncytial virus (rsv) often bear low viral loads that stay below the detection limits of commercial assays. a more sensitive detection of rsv infections can improve patient management, guide containment strategies, and possibly prevent morbidity and mortality among populations most severely affected by rsv.200919758841
[construction of minireplicon of human respiratory syncytial virus].the reverse genetics technology is an important way to develop genetically engineered attenuated living human respiratory syncytial virus (rsv) vaccine candidates. as the pilot experiment,it is necessary to prepare rsv minireplicon and investigate its biological activity.200919835166
potent high-affinity antibodies for treatment and prophylaxis of respiratory syncytial virus derived from b cells of infected patients.native human abs represent attractive drug candidates; however, the low frequency of b cells expressing high-quality abs has posed a barrier to discovery. using a novel single-cell phenotyping technology, we have overcome this barrier to discover human abs targeting the conserved but poorly immunogenic central motif of respiratory syncytial virus (rsv) g protein. for the entire cohort of 24 subjects with recent rsv infection, b cells producing abs meeting these stringent specificity criteria wer ...200919841167
evaluation of nanogen mgb alert detection reagents in a multiplex real-time pcr for influenza virus types a and b and respiratory syncytial virus.a multiplex real-time rt-pcr assay that detects influenza a, influenza b and respiratory syncytial virus (rsv) using the mgb alert influenza a&b/rsv detection reagent ruo (nanogen, san diego, ca) was developed. the nanogen detection reagents consist of pcr primers and minor groove binder-conjugated hybridization probes for each virus and an internal control. virus typing was determined by post-pcr melt curve analysis. a non-competitive armored rna internal control was co-extracted with each samp ...200919061916
positive selection results in frequent reversible amino acid replacements in the g protein gene of human respiratory syncytial virus.human respiratory syncytial virus (hrsv) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. multiple lineages of the hrsva and hrsvb serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. in the present study we utilized phylogenetic methods to detect ...200919119418
comparison of viral isolation and multiplex real-time reverse transcription-pcr for confirmation of respiratory syncytial virus and influenza virus detection by antigen immunoassays.we evaluated the prodesse proflu-1 real-time reverse transcription-pcr multiplex assay with the smartcycler instrument for the detection of human respiratory syncytial virus (rsv) and influenza a and b viruses in comparison to conventional cell culture and antigen immunoassays with the bd directigen a+b and binax now rsv assays over two successive respiratory virus seasons. ninety-two percent of the 361 specimens tested were nasopharyngeal aspirates obtained from individual patients, of which 11 ...200919129410
cigarette smoke alters respiratory syncytial virus-induced apoptosis and replication.individuals exposed to cigarette smoke have a greater number and severity of viral infections, including respiratory syncytial virus (rsv) infections, than do nonsmokers, but the cellular mechanism is unknown. our objective was to determine the mechanism by which cigarette smoke augments viral infection. we hypothesize that cigarette smoke causes necrosis and prevents virus-induced cellular apoptosis, and that this is associated with increased inflammation and viral replication. primary airway e ...200919131644
human respiratory syncytial virus nonstructural protein ns2 antagonizes the activation of beta interferon transcription by interacting with rig-i.a wide variety of rna viruses have been shown to produce proteins that inhibit interferon (ifn) production and signaling. for human respiratory syncytial virus (rsv), the nonstructural ns1 and ns2 proteins have been shown to block ifn signaling by causing the proteasomal degradation of stat2. in addition, recombinant rsvs lacking either ns1 or ns2 induce more ifn production than wild-type (wt) rsv in infected cells. however, the mechanisms by which the ns proteins perform this function are unkno ...200919193793
human piv-2 recombinant sendai virus (rsev) elicits durable immunity and combines with two additional rsevs to protect against hpiv-1, hpiv-2, hpiv-3, and rsv.the human parainfluenza viruses (hpivs) and respiratory syncytial viruses (rsvs) are the leading causes of hospitalizations due to respiratory viral disease in infants and young children, but no vaccines are yet available. here we describe the use of recombinant sendai viruses (rsevs) as candidate vaccine vectors for these respiratory viruses in a cotton rat model. two new sendai virus (sev)-based hpiv-2 vaccine constructs were generated by inserting the fusion (f) gene or the hemagglutinin-neur ...200919200447
[expression and purification of a secreted form of fusion glycoprotein of human respiratory syncytial virus encoded by recombinant baculovirus].to study the expression and purification of a secreted form of fusion glycoprotein (sf) of human respiratory syncytial virus (rsv) encoded by recombinant baculovirus.200920387479
[the correlation factor about respiratory syncytial virus bronchiolitis and post-bronchiolitis wheezing in infant].to observe the correlation factor about early-life rsv bronchiolitis and sequential recurrent wheezing for two years.200920387490
[genetic characterization of the n protein of subgroups a and b human respiratory syncytial viruses].to clarify the genetic characteristics of n protein coding region of hrsv isolates from beijing and genbank downloaded sequences.200920104752
antiviral activity of nrf2 in a murine model of respiratory syncytial virus disease.respiratory syncytial virus (rsv) is the most frequent cause of significant lower respiratory illness in infants and young children, but its pathogenesis is not fully understood. the transcription factor nrf2 protects lungs from oxidative injury and inflammation via antioxidant response element (are)-mediated gene induction.200918931336
bronchiolitis: from empiricism to scientific evidence.bronchiolitis is the most common viral infection of the lower respiratory tract in infants in their first year of life, with an incidence peak between 3 and 9 months of age. the clinical profile of bronchiolitis results from the inflammatory obstruction of the small airways. the etiological agent involved is respiratory syncytial virus (rsv) in more than 50% of cases. the first international guidelines on the management of children with bronchiolitis have recently been published. the first was p ...200919322125
ari situation in our country: aren't we oblivious of bronchiolitis in bangladesh?ari/pneumonia has been the leading cause of morbidity and mortality in under five children for a long time. ari control/integrated management of childhood illness (imci) program have been in progress in the country for more than a decade. there have been recent reports of outbreak of rsv bronchiolitis in the country. this study was done to determine the causes of death and morbidity of under five children with possible explanations. a cross sectional national survey was conducted between january ...200919377432
formulation of bovine respiratory syncytial virus fusion protein with cpg oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances humoral and cellular responses and induces a protective type 1 immune response in mice.respiratory syncytial virus (rsv) is the leading cause of serious respiratory tract disease in children and calves; however, rsv vaccine development has been slow due to early observations that formalin-inactivated vaccines induced th2-type immune responses and led to disease enhancement upon subsequent exposure. hence, there is a need for novel adjuvants that will promote a protective th1-type or balanced immune response against rsv. cpg oligodeoxynucleotides (odns), indolicidin, and polyphosph ...200919386785
gene expression of nucleic acid-sensing pattern recognition receptors in children hospitalized for respiratory syncytial virus-associated acute bronchiolitis.given the critical role of pattern recognition receptors (prrs) in acid nucleic recognition in the initiation of innate immunity and the orchestration of adaptive immunity, the aim of this study was to determine whether any heterogeneity of prr expression in the airway tracts of infants with respiratory syncytial virus (rsv) infection might explain the broad clinical spectrum of rsv-associated bronchiolitis in infants. for this purpose, the levels of melanoma differentiation-associated protein-5 ...200919386802
genetic variability of group a human respiratory syncytial virus strains circulating in germany from 1998 to 2007.the variability between respiratory syncytial virus (rsv) strains is one of the features of rsv infections that might contribute to the ability of the virus to infect people repeatedly and cause yearly outbreaks. to study the molecular epidemiology of rsv, more than 1,400 rsv isolates from human nasopharyngeal aspirates or nasal or throat swabs from patients with respiratory illness were identified and differentiated by taqman reverse transcription-pcr into groups a and b. rsv group a was domina ...200919386848
chlamydia trachomatis respiratory infection in dutch infants.chlamydia trachomatis is the most common bacterial pathogen causing sexually transmitted infections in dutch adults. as prenatal screening for c trachomatis and treatment of pregnant women is not routine practice in the netherlands, perinatal transmission of c trachomatis may therefore occur. the presence of c trachomatis in infants less than 6 months of age who presented with respiratory complaints to the erasmus mc-sophia hospital was evaluated. respiratory specimens, primarily nasopharyngeal ...200919395401
recurrent wheezing after respiratory syncytial virus or non-respiratory syncytial virus bronchiolitis in infancy: a 3-year follow-up.recent studies have suggested that rhinovirus-associated early wheezing is a greater risk factor for development of recurrent wheezing in children than is early wheezing associated with respiratory syncytial virus (rsv). we determined the development of recurrent wheezing in young children within 3 years after hospitalization for rsv or non-rsv bronchiolitis.200919416146
surveillance for healthcare-acquired febrile respiratory infection in pediatric hospitals participating in the canadian nosocomial infection surveillance program.to determine the rates of healthcare-acquired febrile respiratory infection (ha-fri) in canadian pediatric hospitals and to determine the vaccination status of patients with healthcare-acquired respiratory syncytial virus (rsv) infection, influenza, or pneumococcal infection who were also eligible for immunoprophylaxis.200919496653
rna interference-mediated silencing of the respiratory syncytial virus nucleocapsid defines a potent antiviral strategy.we describe the design and characterization of a potent human respiratory syncytial virus (rsv) nucleocapsid gene-specific small interfering rna (sirna), aln-rsv01. in in vitro rsv plaque assays, aln-rsv01 showed a 50% inhibitory concentration of 0.7 nm. sequence analysis of primary isolates of rsv showed that the sirna target site was absolutely conserved in 89/95 isolates, and aln-rsv01 demonstrated activity against all isolates, including those with single-mismatch mutations. in vivo, intrana ...200919506055
respiratory syncytial virus and other respiratory viruses in the setting of bone marrow transplantation.several epidemiologic studies have enhanced our understanding of the impact of respiratory viruses on bone marrow transplant recipients.200919532020
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
[construction and identification of replication deficient recombinant adenovirus encoding f gene of subgroup a human respiratory syncytial virus].a strain of replication deficient recombinant adenvirus encoding fusion glycoprotein (f) of subgroup a human respiratory syncytial virus (rsv) was constructed and the expression of f was identified.200819544635
potential anti-respiratory syncytial virus lead compounds from aglaia species.although the global prevalence of respiratory syncytial virus (rsv) infection, especially among infants and young children is on the increase, there are only limited therapeutic options for treatment of this disease. therefore, the search for novel antiviral inhibitors of rsv has become more intensive. in a pilot screening of eighteen compounds from various aglaia species for anti-rsv activity, we identified dammarenolic acid (ignt1), aglaiol (dupt1) and niloticin (cuct1) as potential anti-rsv c ...200818972843
one-step reverse transcriptase polymerase chain reaction for the diagnosis of respiratory syncytial virus in children.human respiratory syncytial virus (hrsv) is the main cause of acute lower respiratory tract infections in infants and children. rapid diagnosis is required to permit appropriate care and treatment and to avoid unnecessary antibiotic use. reverse transcriptase (rt-pcr) and indirect immunofluorescence assay (ifa) methods have been considered important tools for virus detection due to their high sensitivity and specificity. in order to maximize use-simplicity and minimize the risk of sample cross-c ...200818068812
editorial commentary: respiratory viral infections in developing countries: common, severe, and unrecognized. 200818171214
viral infection in asthma.in bronchial asthma, respiratory virus infection involves several issues: 1) respiratory virus infection in infancy is a risk factor for, and may predispose to, the development of asthma later in life; 2) respiratory virus infection is associated with the acute exacerbation of bronchial asthma; and, 3) glucocorticosteroids (gc) are not adequate for controlling asthma-related symptoms upon respiratory virus infection. various cells, inflammatory mediators and cytokines participate in the producti ...200818209504
specificity and functional interaction of the polymerase complex proteins of human and avian metapneumoviruses.human metapneumovirus (hmpv) and avian metapneumovirus (ampv) have a similar genome organization and protein composition, but a different host range. ampv subgroup c (ampv-c) is more closely related to hmpv than other ampvs. to investigate the specificity and functional interaction of the polymerase complex proteins of human and avian metapneumoviruses, a minireplicon system was generated for ampv-c and used in combination with minireplicon systems for hmpv lineages a1 and b1. viral rna-like mol ...200818343839
human and bovine respiratory syncytial virus vaccine research and development.human (hrsv) and bovine (brsv) respiratory syncytial viruses (rsv) are two closely related viruses, which are the most important causative agents of respiratory tract infections of young children and calves, respectively. brsv vaccines have been available for nearly 2 decades. they probably have reduced the prevalence of rsv infection but their efficacy needs improvement. in contrast, despite decades of research, there is no currently licensed vaccine for the prevention of hrsv disease. developm ...200817720245
positive natural selection in the evolution of human metapneumovirus attachment glycoprotein.human metapneumovirus (hmpv), a newly discovered virus of the family paramyxoviridae, has been associated with upper and lower respiratory tract infections in different age groups in many countries. the putative attachment (g) glycoprotein of this virus was previously reported to have shown more extensive nucleotide and deduced amino acid sequence polymorphism than any other genomic regions of this virus, leading to four sub-lineages. using a maximum likelihood-based codon substitution model of ...200817931731
identification and evaluation of a highly effective fusion inhibitor for human metapneumovirus.human metapneumovirus (hmpv) can cause acute upper and lower respiratory tract infections that are particularly severe in young children, elderly subjects, and immunocompromised patients. to date, no treatments or vaccines are available for hmpv infections. our objective was to assess the inhibitory potential of several peptides derived from the heptad repeat a and b (hra and hrb) domains of the hmpv fusion protein. nine candidate peptides were expressed in escherichia coli or obtained synthetic ...200817967906
dual role of nox2 in respiratory syncytial virus- and sendai virus-induced activation of nf-kappab in airway epithelial cells.human respiratory syncytial virus (rsv), a member of the paramyxoviridae family, is the most important viral agent of pediatric respiratory tract disease worldwide. human airway epithelial cells (aec) are the primary targets of rsv. aec are responsible for the secretion of a wide spectrum of cytokines and chemokines that are important mediators of the exacerbated airway inflammation triggered by the host in response to rsv infection. nf-kappab is a key transcription factor responsible for the re ...200818453612
[re: utility of real time polymerase chain reaction in the diagnosis of respiratory syncytial virus infection among adult patients]. 200818483647
use of the rapid antigenic test to determine the duration of isolation in infants hospitalized for respiratory syncytial virus infections.infants hospitalized for bronchiolitis associated with respiratory syncytial virus are isolated for the duration of their hospitalization. this article reviews whether a negative rapid antigenic test could be used to shorten the duration of isolation measures. rapid respiratory syncytial virus tests were performed from day 3 on alternate days in all patients hospitalized for bronchiolitis. isolation measures were removed when the test result was negative. the result of the antigenic test was con ...200818509148
rsv infection--an immune balancing act: commentary on the article by bem et al. on page 650. 200818520329
nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells.human respiratory syncytial virus (rsv) is the most important agent of serious pediatric respiratory tract disease worldwide. one of the main characteristics of rsv is that it readily reinfects and causes disease throughout life without the need for significant antigenic change. the virus encodes nonstructural protein 1 (ns1) and ns2, which are known to suppress type i interferon (ifn) production and signaling. in the present study, we monitored the maturation of human monocyte-derived myeloid d ...200818562519
soluble g protein of respiratory syncytial virus inhibits toll-like receptor 3/4-mediated ifn-beta induction.monocyte-derived dendritic cells (mdcs) recognize viral rna extrinsically by toll-like receptor (tlr) 3 on the membrane and intrinsically retinoic acid-inducible gene i (rig-i)/melanoma differentiation-associated gene 5 (mda5) in the cytoplasm to induce type i ifns and mdc maturation. when mdcs were treated with live or uv-irradiated respiratory syncytial virus (rsv), early ( approximately 4 h) induction of ifn-beta usually occurs in other virus infections was barely observed. live rsv subsequen ...200818611945
respiratory syncytial virus uses a vps4-independent budding mechanism controlled by rab11-fip2.respiratory syncytial virus (rsv) infects polarized epithelia, which have tightly regulated trafficking because of the separation and maintenance of the apical and basolateral membranes. previously we established a link between the apical recycling endosome (are) and the assembly of rsv. the current studies tested the role of a major are-associated protein, rab11 family interacting protein 2 (fip2) in the virus life cycle. a dominant-negative form of fip2 lacking its n-terminal c2 domain reduced ...200818621683
incidence and risk factors of lower respiratory tract illnesses during infancy in a mediterranean birth cohort.to investigate the incidence rate, viral respiratory agents and determinants of lower respiratory tract illnesses (lrtis) in infants younger than 1 year.200818631341
improved outcomes with home-based administration of palivizumab: results from the 2000-2004 palivizumab outcomes registry.palivizumab outcomes registry data collected during 4 years were examined to assess compliance and respiratory syncytial virus (rsv) hospitalization rates in high-risk children receiving palivizumab prophylaxis at home compared with an outpatient setting.200818776822
prevalence and clinical aspects of respiratory syncytial virus a and b groups in children seen at hospital de clínicas of uberlândia, mg, brazil.respiratory syncytial virus (rsv) is well recognized as the most important pathogen causing acute respiratory disease in infants and young children, mainly in the form of bronchiolitis and pneumonia. two major antigenic groups, a and b, have been identified; however, there is disagreement about the severity of the diseases caused by these two types. this study investigated a possible association between rsv groups and severity of disease. reverse transcription-polymerase chain reaction was used ...200818797752
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
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