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effects of surface material, ventilation, and human behavior on indirect contact transmission risk of respiratory infection.infectious particles can be deposited on surfaces. susceptible persons who contacted these contaminated surfaces may transfer the pathogens to their mucous membranes via hands, leading to a risk of respiratory infection. the exposure and infection risk contributed by this transmission route depend on indoor surface material, ventilation, and human behavior. in this study, quantitative infection risk assessments were used to compare the significances of these factors. the risks of three pathogens ...201424955468
characterization of recombinant influenza a virus as a vector expressing respiratory syncytial virus fusion protein epitopes.respiratory syncytial virus (rsv) is the most common cause of respiratory infection in infants and the elderly, and no vaccine against this virus has yet been licensed. here, we report a recombinant pr8 influenza virus with the rsv fusion (f) protein epitopes of the subgroup a gene inserted into the influenza virus non-structural (ns) gene (rflu/rsv/f) that was generated as an rsv vaccine candidate. the rescued viruses were assessed by microscopy and western blotting. the proper expression of ns ...201424914066
the pulmonary localization of virus-specific t lymphocytes is governed by the tissue tropism of infection.the migration of pathogen-specific t cells into nonlymphoid tissues, such as the lung, is critical to control peripheral infections. use of in vivo intravascular labeling of leukocytes has allowed for improved discrimination between cells located in the blood from cells present within peripheral tissues, such as the lung. this is particularly important in the lung, which is comprised of an intricate network of blood vessels that harbors a large proportion of the total blood volume at any given t ...201424899187
screening of respiratory pathogens by respiratory multi well system (mws) r-gene™ assay in hospitalized patients.novel respiratory viruses have been identified as possible agents of upper and lower respiratory tract infections. multiplex real-time pcrs have been developed to identify clinically relevant respiratory pathogens. in this study, 178 respiratory samples already screened for influenza virus types a and b by flu a/b asr real-time pcr kit were retrospectively analyzed with the respiratory multi well system (mws) r-gene™ real-time pcr kit which detects a wide spectrum of respiratory pathogens. the g ...201424858651
egfr activation suppresses respiratory virus-induced irf1-dependent cxcl10 production.airway epithelial cells are the primary cell type involved in respiratory viral infection. upon infection, airway epithelium plays a critical role in host defense against viral infection by contributing to innate and adaptive immune responses. influenza a virus, rhinovirus, and respiratory syncytial virus (rsv) represent a broad range of human viral pathogens that cause viral pneumonia and induce exacerbations of asthma and chronic obstructive pulmonary disease. these respiratory viruses induce ...201424838750
respiratory viruses in exacerbations of non-cystic fibrosis bronchiectasis in children.respiratory viral infections precipitate exacerbations of chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease though similar data in non-cystic fibrosis (cf) bronchiectasis are missing. our study aimed to determine the point prevalence of viruses associated with exacerbations and evaluate clinical and investigational differences between virus-positive and -negative exacerbations in children with bronchiectasis.201424819370
house dust exposure mediates gut microbiome lactobacillus enrichment and airway immune defense against allergens and virus infection.exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. protected animals exhibited significant reduction in the total number of airway t cells, down-regulation of th2-related airway responses, as ...201424344318
probiotic-associated aspiration pneumonia due to lactobacillus rhamnosus.lactobacilli are low-virulence, commensal organisms of the gastrointestinal and genitourinary tracts and are commonly used as "probiotic supplements." herein, we describe an episode of respiratory syncytial virus (rsv) bronchiolitis with bacterial superinfection secondary to administration of lactobacillus rhamnosus in an 11-month-old female with trisomy 21.201424899028
immunobiotic lactobacilli reduce viral-associated pulmonary damage through the modulation of inflammation-coagulation interactions.the exacerbated disease due to immune- and coagulative-mediated pulmonary injury during acute respiratory viruses infection results in severe morbidity and mortality. identifying novel approaches to modulate virus-induced inflammation-coagulation interactions could be important alternatives for treating acute respiratory viruses infections. in this study we investigated the effect of the probiotic strain lactobacillus rhamnosus crl1505 on lung tlr3-mediated inflammation, and its ability to modul ...201424394565
prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial.simple and safe strategies for the prevention of viral respiratory tract infections (rtis) are needed.201424131826
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
modified vaccinia virus ankara (mva) as production platform for vaccines against influenza and other viral respiratory diseases.respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hpiv), respiratory syncytial virus (rsv) and coronaviruses are an eminent threat for public health. currently, there are no licensed vaccines available for hpiv, rsv and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. with regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these re ...201425036462
evaluation of a rapid antigen detection point-of-care test for respiratory syncytial virus and influenza in a pediatric hospitalized population in the netherlands.this pilot study evaluates the diagnostic performance of sofia rsv fluorescent immunoassay analyzer (fia) and sofia influenza a + b fia for rapid detection of respiratory syncytial virus and influenza a and b. sofia had a lower-than-expected sensitivity for all viruses and a high rate of false-positive results for influenza b virus.201425241640
influenza and respiratory syncytial viral infections in malaysia: demographic and clinical perspective.respiratory infections represent a major public health problem worldwide. the study aimed to determine the prevalence of respiratory syncytial and influenza virus infections and analyzed in respect to demography and clinical perspective. methods : the specimens were processed by cell culture and immunofluorescent assay (ifa) and real-time reverse transcriptase-pcr (rrt-pcr) for detection of respiratory viruses. results : out of 505 specimens 189 (37.8%) were positive, in which rsv was positive i ...201424639853
influenza virus vaccine expressing fusion and attachment protein epitopes of respiratory syncytial virus induces protective antibodies in balb/c mice.respiratory syncytial virus (rsv) is an important viral pathogen that causes life-threatening respiratory infections in both infants and the elderly; no vaccines are at present available. in this report, we examined the use of influenza virus as a vehicle for production of an experimental rsv vaccine. we used reverse genetics to generate a recombinant influenza a virus with epitopes from the rsv fusion (f) and attachment (g) proteins (rflu/rsv/f+g) in the influenza virus nonstructural (ns1) prot ...201424509239
viral aetiology of acute lower respiratory tract illness in hospitalised paediatric patients of a tertiary hospital: one year prospective study.acute lower respiratory tract infections (alri), ranked as the second leading cause of death are the primary cause of hospitalisation in children. viruses are the most important causative agents of alri.201424399381
comparison of in vitro antiviral activity of tea polyphenols against influenza a and b viruses and structure-activity relationship analysis.influenza poses a particular risk of severe outcomes in the elderly, the very young and those with underlying diseases. tea polyphenols are the natural phenolic compounds in teas, and principally consist of catechins, proanthocyanidins, flavonols, and theaflavins, which antiviral activities have been reported recently. this study is to gain a further insight into potential of various tea polyphenols for inhibiting influenza virus infection. five tea polyphenols exhibited inhibitory activity agai ...201424370660
seasonal evaluation of bioaerosols from indoor air of residential apartments within the metropolitan area in south korea.the aims of the present study were to determine the levels of bioaerosols including airborne culturable bacteria (total suspended bacteria, gram-positive bacteria, staphylococcus, staphylococcus aureus, methicillin-resistant s. aureus (mrsa), and gram-negative bacteria), fungi, endotoxin, and viruses (influenza a, influenza b, respiratory syncytial virus types a/b, parainfluenza virus types 1/2/3, metapnemovirus, and adenovirus) and their seasonal variations in indoor air of residential apartmen ...201424242232
[recombinant human interferon alpha 2b broad-spectrum anti-respiratory viruses pharmacodynamics study in vitro].this study is to investigate the effect of recombinant human interferon alpha 2b against broad-spectrum respiratory viruses in vitro. at the cellular level, the effect of the recombinant human interferon alpha 2b on influenza a virus was detected using real-time fluorescence quantitative rt-pcr. the effects of the recombinant human interferon alpha 2b on influenza b virus, parainfluenza virus, respiratory syncytial virus (rsv) and coronavirus were detected using cytopathic effect (cpe) method. i ...201425757280
novel clinical features of recurrent human respiratory syncytial virus infections.children and elderly individuals are often infected easily and repeatedly with human respiratory syncytial virus (hrsv); however, the features of recurrent infection in the same individual are defined poorly. to clarify the clinical significance of repeated hrsv infections in relation to subgroup epidemiology, this study performed prospective and longitudinal analyses in children with lower respiratory tract infections over 20 consecutive epidemics between 1985 and 2005 at a pediatric outpatient ...201424166209
genetic diversity in the g protein gene of group a human respiratory syncytial viruses circulating in riyadh, saudi arabia.human respiratory syncytial virus (hrsv) is a frequent cause of hospitalization and mortality in children worldwide. the molecular epidemiology and circulation pattern of hrsv in saudi arabia is mostly uncharted. in the current study, the genetic variability and phylogenetic relationships of hrsv type a strains circulating in riyadh province were explored. nasopharyngeal aspirates were collected from hospitalized children with acute respiratory symptoms during the winter-spring seasons of 2007/0 ...201423884633
group b strains of human respiratory syncytial virus in saudi arabia: molecular and phylogenetic analysis.the genetic variability and circulation pattern of human respiratory syncytial virus group b (hrsv-b) strains, identified in riyadh during the winters of 2008 and 2009, were evaluated by partial sequencing of the attachment (g) protein gene. the second hypervariable region (hvr-2) of g gene was amplified by rt-pcr, sequenced and compared to representatives of different hrsv-b genotypes. sequence and phylogenetic analysis revealed that all saudi strains belonged to the genotype ba, which is chara ...201424370974
rapid replacement of human respiratory syncytial virus a with the on1 genotype having 72 nucleotide duplication in g gene.human respiratory syncytial virus (hrsv) is the main cause of severe respiratory illness in young children and elderly people. we investigated the genetic characteristics of the circulating hrsv subgroup a (hrsv-a) to determine the distribution of genotype on1, which has a 72-nucleotide duplication in attachment g gene. we obtained 456 hrsv-a positive samples between october 2008 and february 2013, which were subjected to sequence analysis. the first on1 genotype was discovered in august 2011 an ...201424820343
human respiratory syncytial virus memphis 37 causes acute respiratory disease in perinatal lamb lung.respiratory syncytial virus (rsv) is the leading cause of hospitalization due to respiratory illness among infants and young children of industrialized countries. there is a lack of understanding of the severe disease mechanisms as well as limited treatment options, none of which are fully satisfactory. this is partly due to lack of a relevant animal model of perinatal rsv infection that mimics moderate to severe disease in infants. we and others have shown mild disease in perinatal lambs with e ...201424804166
structural analysis of respiratory syncytial virus reveals the position of m2-1 between the matrix protein and the ribonucleoprotein complex.respiratory syncytial virus (rsv), a member of the paramyxoviridae family of nonsegmented, negative-sense, single-stranded rna genome viruses, is a leading cause of lower respiratory tract infections in infants, young children, and the elderly or immunocompromised. there are many open questions regarding the processes that regulate human rsv (hrsv) assembly and budding. here, using cryo-electron tomography, we identified virus particles that were spherical, filamentous, and asymmetric in structu ...201424760890
[sequence analysis of g glycoprotein gene of human respiratory syncytial virus].to understand the variation of g glycoprotein gene of human respiratory syncytial virus (hrsv) obtained from sichuan in 2010 and determine the dominant genotypes.201424749351
within-host whole-genome deep sequencing and diversity analysis of human respiratory syncytial virus infection reveals dynamics of genomic diversity in the absence and presence of immune pressure.human respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract disease in infants and young children and an important respiratory pathogen in the elderly and immunocompromised. while population-wide molecular epidemiology studies have shown multiple cocirculating rsv genotypes and revealed antigenic and genetic change over successive seasons, little is known about the extent of viral diversity over the course of an individual infection, the origins of novel variants, or ...201424741088
investigation of the role of major respiratory viruses in the aetiology of nasal polyps using polymerase chain reaction technique.objective: we aimed to identify the role of major respiratory viruses in the aetiology of human nasal polyps using polymerase chain reaction technique. methods: thirty patients with nasal polyps and a group of 20 healthy patients (control group) were included in this study. mucosa was obtained from the polyps of patients with nasal polyposis and from the middle turbinate of the control group patients by means of biopsy. the samples were stored at -80 °c until molecular analysis by polymerase cha ...201424735988
a respiratory syncytial virus (rsv) vaccine based on parainfluenza virus 5 (piv5).human respiratory syncytial virus (rsv) is a leading cause of severe respiratory disease and hospitalizations in infants and young children. it also causes significant morbidity and mortality in elderly and immune compromised individuals. no licensed vaccine currently exists. parainfluenza virus 5 (piv5) is a paramyxovirus that causes no known human illness and has been used as a platform for vector-based vaccine development. to evaluate the efficacy of piv5 as a rsv vaccine vector, we generated ...201424717150
the thr205 phosphorylation site within respiratory syncytial virus matrix (m) protein modulates m oligomerization and virus production.human respiratory syncytial virus (rsv) is the most common cause of bronchiolitis and pneumonia in infants and the elderly worldwide; however, there is no licensed rsv vaccine or effective drug treatment available. the rsv matrix (m) protein plays key roles in virus assembly and budding, but the protein interactions that govern budding of infectious virus are not known. in this study, we focus on m protein and identify a key phosphorylation site (thr205) in m that is critical for rsv infectious ...201424672034
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
gene sequence variability of the three surface proteins of human respiratory syncytial virus (hrsv) in texas.human respiratory syncytial virus (hrsv) has three surface glycoproteins: small hydrophobic (sh), attachment (g) and fusion (f), encoded by three consecutive genes (sh-g-f). a 270-nt fragment of the g gene is used to genotype hrsv isolates. this study genotyped and investigated the variability of the gene and amino acid sequences of the three surface proteins of hrsv strains collected from 1987 to 2005 from one center. sixty original clinical isolates and 5 prototype strains were analyzed. seque ...201424625544
enzyme-linked immunospot assay for detection of human respiratory syncytial virus f protein-specific gamma interferon-producing t cells.respiratory syncytial virus (rsv) causes significant disease in elderly adults, and we have previously reported that individuals 65 years of age and older have reduced rsv f protein-specific gamma interferon (ifn-γ)-producing t cells compared to healthy younger adults. to measure rsv f-specific memory t cell responses in the elderly following infection or vaccination, we optimized and qualified an ifn-γ enzyme-linked immunospot (elispot) assay. since peripheral blood mononuclear cells (pbmc) fro ...201424574540
sublingual administration of a helper-dependent adenoviral vector expressing the codon-optimized soluble fusion glycoprotein of human respiratory syncytial virus elicits protective immunity in mice.sublingual (s.l.) immunization has been described as a convenient and safe way to induce mucosal immune responses in the respiratory and genital tracts. we constructed a helper-dependent adenoviral (hdad) vector expressing a condon-optimized soluble fusion glycoprotein (sfsyn) of respiratory syncytial virus (hdad-sfsyn) and explored the potential of s.l. immunization with hdad-sfsyn to stimulate immune responses in the respiratory mucosa. the rsv specific systemic and mucosal immune responses we ...201424560779
proof of principle for epitope-focused vaccine design.vaccines prevent infectious disease largely by inducing protective neutralizing antibodies against vulnerable epitopes. several major pathogens have resisted traditional vaccine development, although vulnerable epitopes targeted by neutralizing antibodies have been identified for several such cases. hence, new vaccine design methods to induce epitope-specific neutralizing antibodies are needed. here we show, with a neutralization epitope from respiratory syncytial virus, that computational prote ...201424499818
mapping of cd8 t cell epitopes in human respiratory syncytial virus l protein.since it has been reported that in humans there is a relationship between human respiratory syncytial virus (hrsv)-specific cytotoxic t lymphocytes and symptom reduction, and that the polymerase (structural l protein) is highly conserved among different strains, this work aimed to identify the cd8 t cell epitopes h-2(d) restricted within the l sequence for immunization purposes.201424480928
genotype circulation pattern of human respiratory syncytial virus in iran.in order to have information on the molecular epidemiology and genetic circulation pattern of human respiratory syncytial virus (hrsv) in iran, we studied the genetic variability of both group a and b hrsv strains during seven consecutive years by sequencing the hypervariable c-terminal domain of g protein. a total of 485 children <2years of age who were negative for influenza viruses, screened for the presence of hrsv in this research. hrsv was detected in 94 (19.38%) of the samples using neste ...201424462624
novel vaccine regimen elicits strong airway immune responses and control of respiratory syncytial virus in nonhuman primates.induction of long-lasting immunity against viral respiratory tract infections remains an elusive goal. using a nonhuman primate model of human respiratory syncytial virus (hrsv) infection, we compared mucosal and systemic immune responses induced by different dna delivery approaches to a novel parenteral dna prime-tonsillar adenoviral vector booster immunization regimen. intramuscular (i.m.) electroporation (ep) of a dna vaccine encoding the fusion protein of hrsv induced stronger systemic immun ...201424453366
crystal structure of the essential transcription antiterminator m2-1 protein of human respiratory syncytial virus and implications of its phosphorylation.the m2-1 protein of the important pathogen human respiratory syncytial virus is a zinc-binding transcription antiterminator that is essential for viral gene expression. we present the crystal structure of full-length m2-1 protein in its native tetrameric form at a resolution of 2.5 å. the structure reveals that m2-1 forms a disk-like assembly with tetramerization driven by a long helix forming a four-helix bundle at its center, further stabilized by contact between the zinc-binding domain and ad ...201424434552
generation and epitope mapping of a sub-group cross-reactive anti-respiratory syncytial virus g glycoprotein monoclonal antibody which is protective in vivo.passively administered antibodies to conserved epitopes on the attachment (g) glycoprotein of human respiratory syncytial virus (hrsv) have potential in the immunoprophylaxis of human infections. this study set out to generate monoclonal antibodies (mabs) recognizing all prevalent lineages of hrsv and capable of immunoprophylaxis in mice. two murine mabs of broad specificity for prevalent virus strains were generated by immunization of mice with hrsv of sub-group a followed by selection of hybri ...201424415460
cd8+ t cell immunity against human respiratory syncytial virus.human respiratory syncytial virus (hrsv) was first discovered in the 1950s, but despite decades of research, a licensed vaccine against it is not available. epidemiological studies indicate that antibodies directed against the fusion protein (f) partially correlate with protection. in addition, an f-specific monoclonal antibody is licensed as a prophylactic treatment in children who are at high risk of developing complications following hrsv infection. therefore, most hrsv-oriented vaccination s ...201425223272
[application possibility of the macrolides for the rs virus infections].human respiratory syncytial virus (rsv) is a major causative agent of respiratory infections. common cold syndrome caused by rs virus, which is prevalent in winter, occasionally develops into bronchitis, bronchiolitis and pneumonia. in particular, severe rs virus infections in infants with underlying cardiopulmonary diseases and with low-birth weight baby have been a problem. furthermore, repetitive rs virus infections occur for the entire lifetime, and the relationship between rs virus infectio ...201425163248
attenuation of human respiratory syncytial virus by genome-scale codon-pair deoptimization.human respiratory syncytial virus (rsv) is the most important viral agent of serious pediatric respiratory-tract disease worldwide. a vaccine or generally effective antiviral drug is not yet available. we designed new live attenuated rsv vaccine candidates by codon-pair deoptimization (cpd). specifically, viral orfs were recoded by rearranging existing synonymous codons to increase the content of underrepresented codon pairs. amino acid coding was completely unchanged. four cpd rsv genomes were ...201425157129
the genetic variability of glycoproteins among respiratory syncytial virus subtype a in china between 2009 and 2013.human respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract infections in infants and children under 5years of age. the novel genotype on1 has a 72-nucleotide duplication, which is the largest duplicated genome portion of rsv. whether the on1 genotype will follow the pattern of the ba genotype, which has a 60-nucleotide duplication, and become the predominant rsv-a strain is a global concern. to obtain information regarding the prevalence of the on1 genotype in ...201425109878
identification of cellular proteins that interact with newcastle disease virus and human respiratory syncytial virus by a two-dimensional virus overlay protein binding assay (vopba).although it is well documented that the initial attachment receptors for newcastle disease virus (ndv) and respiratory syncytial virus (rsv) are sialic acid-containing molecules and glycosaminoglycans respectively, the exact nature of the receptors for both viruses remains to be deciphered. moreover, additional molecules at the host cell surface might be involved in the entry mechanism. with the aim of identifying the cellular proteins that interact with ndv and rsv at the cell surface, we perfo ...201425109545
a comprehensive proteomic view of responses of a549 type ii alveolar epithelial cells to human respiratory syncytial virus infection.human respiratory syncytial virus is a major respiratory pathogen for which there are no suitable antivirals or vaccines. a better understanding of the host cell response to this virus may redress this problem. the present report concerns analysis of multiple independent biological replicates of control and 24 h infected lysates of a549 cells by two different proteomic workflows. one workflow involved fractionation of lysates by in-solution protein ief and individual fractions were digested usin ...201425106423
inhibition of the human respiratory syncytial virus small hydrophobic protein and structural variations in a bicelle environment.the small hydrophobic (sh) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hrsv). sh protein has a single α-helical transmembrane (tm) domain that forms pentameric ion channels. herein, we report the first inhibitor of the sh protein channel, pyronin b, and we have mapped its binding site to a conserved surface of the rsv sh pentamer, at the c-terminal end of the transmembrane domain. the validity of the sh protein structural model used has been confirmed ...201425100835
surface expression of the hrsv nucleoprotein impairs immunological synapse formation with t cells.human respiratory syncytial virus (hrsv) is the leading cause of bronchiolitis and pneumonia in young children worldwide. the recurrent hrsv outbreaks and reinfections are the cause of a significant public health burden and associate with an inefficient antiviral immunity, even after disease resolution. although several mouse- and human cell-based studies have shown that hrsv infection prevents naïve t-cell activation by antigen-presenting cells, the mechanism underlying such inhibition remains ...201425056968
an outbreak of acute respiratory infections due to human respiratory syncytial virus in a nursing home for the elderly in ibaraki, japan, 2014. 201425056086
initial radiographic features as outcome predictor of adult respiratory syncytial virus respiratory tract infection.the purposes of this study were to evaluate the chest radiographic features of adult patients hospitalized for respiratory syncytial virus respiratory tract infections and to assess whether initial chest radiographic findings help predict clinical outcome.201425055260
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
genetic variation of human respiratory syncytial virus among children with fever and respiratory symptoms in shanghai, china, from 2009 to 2012.human respiratory syncytial virus (hrsv) of genus pneumovirus is one of the most common pathogens causing severe acute lower respiratory tract infection in infants and children. no information on the genotype distribution of hrsv is available in east china (e.g. shanghai). from august 2009 to december 2012, 2407 nasopharyngeal swabs were collected from outpatient children with fever and respiratory symptoms in shanghai. hrsv infection was determined using a multiplex rt-pcr assay. the second hyp ...201425046173
rapid spread of the novel respiratory syncytial virus a on1 genotype, central italy, 2011 to 2013.respiratory infections positive for human respiratory syncytial virus (rsv) subtype a were characterised in children admitted to hospitals in rome and ancona (italy) over the last three epidemic seasons. different strains of the novel rsv-a genotype on1, first identified in ontario (canada) in december 2010, were detected for the first time in italy in the following 2011/12 epidemic season. they bear an insertion of 24 amino acids in the g glycoprotein as well as amino acid changes likely to cha ...201425011065
polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation.human respiratory syncytial virus (hrsv) has two major surface glycoproteins (g and f) anchored in the lipid envelope. membrane fusion promoted by hrsv_f occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the f trimer. one of these changes results in assembly of two heptad repeat sequences (hra and hrb) into a six-helix bundle (6hb) motif. to assist in distinguishing pre- and post-fusion conformations of hrsv_f, we have prep ...201425010277
differentiation of th subsets inhibited by nonstructural proteins of respiratory syncytial virus is mediated by ubiquitination.human respiratory syncytial virus (rsv), a major cause of severe respiratory diseases, constitutes an important risk factor for the development of subsequent asthma. however, the mechanism underlying rsv-induced asthma is poorly understood. viral non-structural proteins ns1 and ns2 are critically required for rsv virulence; they strongly suppress ifn-mediated innate immunity of the host cells. in order to understand the effects of ns1 and ns2 on differentiation of th subsets, we constructed lent ...201424992002
new method for the visual detection of human respiratory syncytial virus using reverse transcription loop-mediated amplification.human respiratory syncytial virus (hrsv) is a seasonal respiratory pathogen that causes respiratory infection in children and the elderly. a new, reverse transcriptase loop-mediated isothermal amplification (rt-lamp) assay was developed for the rapid (within 1h), simultaneous detection of a and b group hrsv. primers specific for groups a and b were designed to amplify the n and l genes of hrsv, respectively. a fluorescent dye, calcein, was used as an indicator for the endpoint visual detection a ...201424925133
impaired immune response to vaccination against infection with human respiratory syncytial virus at advanced age.elderly humans are prone to severe infection with human respiratory syncytial virus (hrsv). the aging of today's human population warrants the development of protective vaccination strategies aimed specifically at the elderly. this may require special approaches due to deteriorating immune function. to design and test vaccination strategies tailored to the elderly population, we need to understand the host response to hrsv vaccination and infection at old age. moreover, the preclinical need for ...201424920795
quantitative investigation of the affinity of human respiratory syncytial virus phosphoprotein c-terminus binding to nucleocapsid protein.there are no approved small molecule drug therapies for human respiratory syncytial virus (hrsv), a cause of morbidity and mortality in at-risk newborns, the immunocompromised, and the elderly. we have investigated as a potential novel hrsv drug target the protein-protein interaction between the c-terminus of the viral phosphoprotein (p) and the viral nucleocapsid protein (n), components of the ribonucleoprotein complex that contains, replicates, and transcribes the viral rna genome. earlier wor ...201425407889
specificity and effector functions of human rsv-specific igg from bovine milk.respiratory syncytial virus (rsv) infection is the second most important cause of death in the first year of life, and early rsv infections are associated with the development of asthma. breastfeeding and serum igg have been shown to protect against rsv infection. yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins.201425375837
functional and immune response to respiratory syncytial virus infection in aged balb/c mice: a search for genes determining disease severity.recent studies have demonstrated that respiratory syncytial virus (rsv) is a significant cause of morbidity and mortality in the elderly. the cellular mechanisms that determine the host's susceptibility and severity of the disease are not well understood. in this study, we sought a mouse model of human respiratory disease by studying the functional and cellular response to rsv in aged animals.201424354462
combining single rna sensitive probes with subdiffraction-limited and live-cell imaging enables the characterization of virus dynamics in cells.the creation of fluorescently labeled viruses is currently limited by the length of imaging observation time (e.g., labeling an envelope protein) and the rescue of viral infectivity (e.g., encoding a gfp protein). using single molecule sensitive rna hybridization probes delivered to the cytoplasm of infected cells, we were able to isolate individual, infectious, fluorescently labeled human respiratory syncytial virus virions. this was achieved without affecting viral mrna expression, viral prote ...201424351207
molecular epidemiology of human respiratory syncytial virus over three consecutive seasons in latvia.lower respiratory tract infections caused by the human respiratory syncytial virus (hrsv) represent an immense burden of the disease, especially in young children. this study aimed to investigate the evolutionary history of hrsv strains isolated in the children's clinical university hospital (riga, latvia) over three consecutive hrsv seasons. of 207 samples from children hospitalized with lower respiratory tract infections, 88 (42.5%) tested positive for hrsv by rt-pcr. the seasonal activity sta ...201424301088
molecular characterization of human respiratory syncytial virus, 2010-2011: identification of genotype on1 and a new subgroup b genotype in thailand.this study reports the molecular epidemiology and genetic characterization of human respiratory syncytial virus (rsv) samples collected in thailand from january 2010 to december 2011. in total, 1,315 clinical samples were collected from bangkok and khon kaen provinces and were screened by semi-nested pcr for rsv infection. we found 74 samples (27.7 %) and 71 samples (6.8 %) to be rsv positive for bangkok and khon kaen, respectively, and we sequenced 122 of these samples. phylogenetic analysis re ...201424068580
[epidemiological study of respiratory viruses detected in patients under two years old who required admission because of lower respiratory disease].the etiologic role of recently identified respiratory viruses for lower respiratory tract disease (lrtd) remains unclear in japan. the purpose of this study was to investigate the prevalence of respiratory viruses in young children with lrtd. we prospectively examined 721 children who were under two years old and admitted to a single medical center in japan with lrtd between april 2007 and march 2012. viral nucleotic acids were taken from their nasal swabs. each sample was examined with (rt-) pc ...201425199375
association of meteorological factors with childhood viral acute respiratory infections in subtropical china: an analysis over 11 years.the objective of this study was to obtain a better understanding of the effects of meteorological factors on the prevalence and seasonality of common respiratory viruses in china, which has a subtropical climate. a retrospective study was conducted by identifying children admitted to a hospital with acute respiratory infections due to seven common viruses between january 2001 and december 2011. a total of 42,104 nasopharyngeal samples were tested for respiratory syncytial virus (rsv), influenza ...201424114148
hyperferritinemia in neonatal and infantile human parechovirus-3 infection in comparison with other infectious diseases.human parechovirus-3 (hpev-3) has been associated with severe clinical manifestations in neonates and infants in the form of sepsis or hemophagocytic lymphohistiocytosis (hlh)-like illness. to clarify the clinical features of hpev-3 infection, we compared clinical signs and laboratory findings among enteroviruses (evs), hpev-3, and other infections. participants were 26 febrile infants in whom evs (n = 20) or hpev-3 (n = 6) were isolated from throat swab or fecal specimens. clinical and laborato ...201424462418
modeling human respiratory viral infections in the cotton rat (sigmodon hispidus).for over three decades, cotton rats have been a preferred model for human respiratory syncytial virus (rsv) infection and pathogenesis, and a reliable model for an impressive list of human respiratory pathogens including adenoviruses, para influenza virus, measles, and human metapneumo virus. the most significant contribution of the cotton rat to biomedical research has been the development of anti-rsv antibodies for prophylactic use in high-risk infants. more recently, however, the cotton rat m ...201425635205
central nervous system alterations caused by infection with the human respiratory syncytial virus.worldwide, the human respiratory syncytial virus (hrsv) is the leading cause of infant hospitalization because of acute respiratory tract infections, including severe bronchiolitis and pneumonia. despite intense research, to date there is neither vaccine nor treatment available to control hrsv disease burden globally. after infection, an incubation period of 3-5 days is usually followed by symptoms, such as cough and low-grade fever. however, hrsv infection can also produce a larger variety of s ...201425316031
protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein.infections with human respiratory syncytial virus (hrsv) occur globally in all age groups and can have devastating consequences in young infants. we demonstrate that a vaccine based on the extracellular domain (she) of the small hydrophobic (sh) protein of hrsv, reduced viral replication in challenged laboratory mice and in cotton rats. we show that this suppression of viral replication can be transferred by serum and depends on a functional igg receptor compartment with a major contribution of ...201425298406
molecular evolution of human respiratory syncytial virus attachment glycoprotein (g) gene of new genotype on1 and ancestor na1.we conducted a comprehensive genetic analysis of the c-terminal 3rd hypervariable region of the attachment glycoprotein (g) gene in human respiratory syncytial virus subgroup a (hrsv-a) genotype on1 (93 strains) and ancestor na1 (125 strains). genotype on1 contains a unique mutation of a 72 nucleotide tandem repeat insertion (corresponding to 24 amino acids) in the hypervariable region. the bayesian markov chain monte carlo (mcmc) method was used to conduct phylogenetic analysis and a time scale ...201425283803
visualizing the replication of respiratory syncytial virus in cells and in living mice.respiratory syncytial virus (rsv) is the most important cause of severe lower-respiratory tract disease in calves and young children, yet no human vaccine nor efficient curative treatments are available. here we describe a recombinant human rsv reverse genetics system in which the red fluorescent protein (mcherry) or the firefly luciferase (luc) genes are inserted into the rsv genome. expression of mcherry and luc are correlated with infection rate, allowing the monitoring of rsv multiplication ...201425277263
respiratory syncytial virus: pathology, therapeutic drugs and prophylaxis.human respiratory syncytial virus (hrsv) is the leading cause of lower respiratory tract diseases, affecting particularly newborns and young children. this virus is able to modulate the immune response, generating a pro-inflammatory environment in the airways that causes obstruction and pulmonary alterations in the infected host. to date, no vaccines are available for human use and the first vaccine that reached clinical trials produced an enhanced hrsv-associated pathology 50 years ago, resulti ...201425268876
in silico approach towards designing virtual oligopeptides for hrsv.hrsv (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. in the present study, in silico docking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-hrsv agents. additional simulations were conducted to study the conformational ...201425525622
modulation of host adaptive immunity by hrsv proteins.globally, the human respiratory syncytial virus (hrsv) is the major cause of lower respiratory tract infections (lrtis) in infants and children younger than 2 years old. furthermore, the number of hospitalizations due to lrtis has shown a sustained increase every year due to the lack of effective vaccines against hrsv. thus, this virus remains as a major public health and economic burden worldwide. the lung pathology developed in hrsv-infected humans is characterized by an exacerbated inflammato ...201425513775
clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years.most wheezing episodes in infants are caused and exacerbated by virus-induced lower respiratory tract infections. however, there are few reports of epidemiologic and clinical virus-specific research with a focus on virus-induced wheezing. the purpose of the current study was to characterize the clinical presentation of virus-induced wheezing in pediatric patients <3 years of age who were hospitalized with lower respiratory tract infections. of the 412 patients in the study, 216 were followed for ...201424535712
viral etiology of bronchiolitis among pediatric inpatients in northern taiwan with emphasis on newly identified respiratory viruses.viral etiology of bronchiolitis in children in taiwan has been fragmentary. we conducted a prospective study to figure out the viral epidemiology of bronchiolitis in taiwan.201423040235
immunogenicity in mice of human metapneumovirus with a truncated sh glycoprotein.the sh glycoprotein of human metapneumovirus (hmpv) is twice the size of that of human respiratory syncytial virus and possesses a large, hydrophilic luminal domain. the glycoprotein is located on the surface of the virion and of virus infected cells and, if immunogenic, might be expected to play a role in anti-viral immunity. initial attempts to study anti-sh antibody immunogenicity were thwarted by the instability of the sh gene on passage both in human bronchial epithelial cells and in mice. ...201424009128
seasonal occurrence of human metapneumovirus infections in croatia.human metapneumovirus (hmpv) is 1 of the commonest causes of viral ari especially among pediatric patients. its incidence varies from year to year in countries belonging to moderate climate zone. the aim of this study was to investigate epidemiologic characteristics of hmpv infections in croatia.201423989108
seasonality and prevalence of respiratory pathogens detected by multiplex pcr at a tertiary care medical center.respiratory tract infections (rtis) are a leading cause of mortality and morbidity. seasonality has been reported for many viruses, including influenza virus, respiratory syncytial virus (rsv), and the recently described human metapneumovirus (hmpv). we hypothesize that the availability of rapid, multiplex pcr diagnostics will provide better clinical care and new insights into the etiology and clinical spectrum of rtis. we conducted a retrospective analysis of the incidence of respiratory pathog ...201423881085
[viral etiology in children with acute lower respiratory tract infections plus platelet disorders in changsha, china: an analysis of 255 cases].to investigate the viral etiology in hospitalized children with acute lower respiratory tract infections (alrti) plus platelet disorders.201424750840
population-based incidence of severe acute respiratory virus infections among children aged <5 years in rural bangladesh, june-october 2010.better understanding the etiology-specific incidence of severe acute respiratory infections (saris) in resource-poor, rural settings will help further develop and prioritize prevention strategies. to address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of saris among children in rural bangladesh.201424587163
chimeric bovine/human parainfluenza virus type 3 expressing respiratory syncytial virus (rsv) f glycoprotein: effect of insert position on expression, replication, immunogenicity, stability, and protection against rsv infection.a recombinant chimeric bovine/human parainfluenza type 3 virus (rb/hpiv3) vector expressing the respiratory syncytial virus (rsv) fusion f glycoprotein previously exhibited disappointing levels of rsv f immunogenicity and genetic stability in children (d. bernstein et al., pediatr. infect. dis. j. 31:109-114, 2012; c.-f. yang et al., vaccine 31:2822-2827, 2013). to investigate parameters that might affect vaccine performance and stability, we constructed and characterized rb/hpiv3 viruses expres ...201424478424
molecular evolution of the haemagglutinin-neuraminidase gene in human parainfluenza virus type 3 isolates from children with acute respiratory illness in yamagata prefecture, japan.we conducted detailed genetic analyses of the haemagglutinin-neuraminidase (hn) gene in 272 human parainfluenza virus type 3 (hpiv3) isolates from children with acute respiratory illness during the period 2002-2009 in yamagata prefecture, japan. a phylogenetic tree reconstructed by the bayesian markov chain monte carlo method showed that the strains diversified at around 1946 and that the rate of molecular evolution was 1.10×10(-3) substitutions per site per year. identity was high among the pre ...201424464692
sendai virus-based rsv vaccine protects against rsv challenge in an in vivo maternal antibody model.respiratory syncytial virus (rsv) is the cause of significant morbidity and mortality among infants, and despite decades of research there remains no licensed vaccine. sevrsv is a sendai virus (sev)-based live intranasal vaccine that expresses the full length rsv fusion (f) gene. sev is the murine counterpart of human parainfluenza virus type 1. given that the target population of sevrsv is young infants, we questioned whether maternal antibodies typical of this age group would inhibit sevrsv va ...201424721531
respiratory syncytial virus- and human metapneumovirus-associated emergency department and hospital burden in adults.determine the burden of illness associated with respiratory syncytial virus (rsv) and human metapneumovirus (hmpv) in adults, especially young adults.201424512531
development of a luciferase immunoprecipitation system assay to detect igg antibodies against human respiratory syncytial virus nucleoprotein.the nucleoprotein of respiratory syncytial virus (rsv-n) is immunogenic and elicits an igg response following infection. the rsv-n gene was cloned into a mammalian expression vector, pren2, and the expressed luciferase-tagged protein (ruc-n) detected anti-rsv-n-specific igg antibodies using a high-throughput immunoprecipitation method (the luciferase immunoprecipitation system [lips]-n(rsv) assay). the specificity of the assay was evaluated using monoclonal antibodies (mabs) and monospecific pre ...201424403526
epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, geneva, switzerland, 2011-2012.few studies have examined the epidemiology of respiratory viral infections in large tertiary centres over more than one season in the era of molecular diagnosis. respiratory clinical specimens received between 1 january 2011 and 31 december 2012 were analysed. respiratory virus testing was performed using a large panel of real-time pcr or rt-pcr. results were analysed according to sample type (upper versus lower respiratory tract) and age group. in all, 2996 (2469 (82.4%) upper; 527 (17.6%) lowe ...201424382326
respiratory viruses are continuously detected in children with chronic tonsillitis throughout the year.to evaluate the oscillations on the viral detection in adenotonsillar tissues from patients with chronic adenotonsillar diseases as an indicia of the presence of persistent viral infections or acute subclinical infections.201425128448
comparison of severe pneumonia caused by human metapneumovirus and respiratory syncytial virus in hospitalized children.the objective of this study is to compare the incidence and clinical characteristics of severe pneumonia caused by human metapneumovirus (hmpv) to respiratory syncytial virus (rsv) infection in children.201425118733
comparison of three commercial rt-pcr systems for the detection of respiratory viruses.due to the insensitivity of rapid tests for respiratory viruses, nucleic acid amplification tests are quickly becoming the standard of care.201425183359
[viral etiologies of hospitalized pneumonia patients aged less than five years in six provinces, 2009-2012].to analyze the viral etiologies of hospitalized pneumonia patients aged less than five years in six provinces during 2009-2012, and to describe the seasonality of the detected viral etiologies.201425174464
a household-based study of acute viral respiratory illnesses in andean children.few community studies have measured the incidence, severity and etiology of acute respiratory illness (ari) among children living at high-altitude in remote rural settings.201424378948
immunization with a recombinant bacillus calmette-guerin strain confers protective th1 immunity against the human metapneumovirus.along with the human respiratory syncytial virus (hrsv), the human metapneumovirus (hmpv) is one of the leading causes of childhood hospitalization and a major health burden worldwide. unfortunately, owing to an inefficient immunological memory, hmpv infection provides limited immune protection against reinfection. furthermore, hmpv can induce an inadequate th2 type immune response that causes severe lung inflammation, leading to airway obstruction. similar to hrsv, it is likely that an effectiv ...201424319265
rates of respiratory virus-associated hospitalization in children aged <5 years in rural northern india.though respiratory viruses are thought to cause substantial morbidity globally in children aged <5 years, the incidence of severe respiratory virus infections in children is unknown in india where 20% of the world's children live.201424269675
identification of human metapneumovirus genotypes a and b from clinical specimens by reverse transcription loop-mediated isothermal amplification.human metapneumovirus (hmpv) has been recognized as an important pathogen for acute respiratory infections in children worldwide and classified into genotypes a and b. reverse transcription loop-mediated isothermal amplification (rt-lamp) assay is a rapid diagnostic method for detecting nucleic acids with a single step under isothermal conditions in less than 1h. rt-lamp targeting the m gene of hmpv was developed for detecting and identifying hmpv genotypes a and b. the detection limit of the ge ...201424269205
respiratory syncytial virus detection in cells and clinical samples by using three new monoclonal antibodies.acute respiratory infections caused by the respiratory syncytial virus (rsv) are important health burdens that affect infants worldwide. rsv is also an important cause of morbidity and disease in adults, which causes enormous economic losses. at the present time, rsv infection is diagnosed by immunofluorescence, test pack and/or pcr, obtaining better results with pcr than with any other technique. the production of new monoclonal antibodies (mabs) capable of detecting rsv in clinical samples is ...201424150877
high prevalence of human metapneumovirus subtype b in cases presenting as severe acute respiratory illness: an experience at tertiary care hospital.a comparatively newly discovered human metapneumovirus (hmpv) has emerged as an important cause of severe acute respiratory illness (sari), second only to respiratory syncytial virus (rsv). rsv and hmpv taxonomically belong to same family and subfamily, and their clinical presentation and seasonal distribution are also seemed to be indistinguishable. present study was planned to know the epidemiology and prevalence of hmpv and rsv in patients presented as sari in a tertiary care hospital.201424131502
incidence and clinical impact of respiratory viruses in adults with cystic fibrosis.viral respiratory infection (vri) is a common cause of pulmonary exacerbations in children with cystic fibrosis (cf). the importance of vri in adult cf populations is unclear.201424127019
a duplex recombinant viral nucleoprotein microbead immunoassay for simultaneous detection of seroresponses to human respiratory syncytial virus and metapneumovirus infections.serologic diagnosis of human respiratory syncytial virus (hrsv) and human metapneumovirus (hmpv) infections has been shown to complement virus detection methods in epidemiologic studies. enzyme immunoassays (eias) using cultured virus lysate antigens are often used to diagnose infection by demonstration of a ≥4-fold rises in antibody titer between acute and convalescent serum pairs. in this study, hrsv and hmpv nucleocapsid (recn) proteins were expressed in a baculovirus system and their perform ...201424859050
[pathogenesis of human metapneumovirus infection and research on attenuated live vaccine].numerous studies have indicated that human metapneumovirus (hmpv) is an important viral pathogen in acute respiratory infections in children, presenting similar manifestations with respiratory syncytial virus (rsv). hmpv infection peaks in the winter-spring season and is more prevalent in younger ages, especially in children less than 1 year old. host innate immune response has been implicated in recognition of pathogen-associated molecular patterns (pamps) of the virus. this recognition occurs ...201424857012
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