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viral specific factors contribute to clinical respiratory syncytial virus disease severity differences in infants.there is a wide range of severity of respiratory syncytial viral (rsv) disease in previously healthy infants. host factors have been well demonstrated to contribute to disease severity differences. however the possibility of disease severity differences being produced by factors intrinsic to the virus itself has rarely been studied.201526473163
anti-rsv prophylaxis efficacy for infants and young children with cystic fibrosis in ireland.there is limited evidence supporting the routine use of palivizumab in paediatric cystic fibrosis (cf) patients to reduce respiratory syncytial virus (rsv) infection and related hospitalisation. despite this, anti-rsv prophylaxis is increasingly common. this is the first report from ireland regarding palivizumab outcomes for children with cf, under 2 years old, despite the greatest prevalence of cf globally.201526473032
epidemiological and clinical profiles of respiratory syncytial virus infection in hospitalized neonates in suzhou, china.this study was designed to explore the epidemiological and clinical profiles of respiratory syncytial virus (rsv) infection in neonates from the suzhou area of china, taking into consideration how climate factors influence disease.201526470889
alum adjuvant enhances protection against respiratory syncytial virus but exacerbates pulmonary inflammation by modulating multiple innate and adaptive immune cells.respiratory syncytial virus (rsv) is well-known for inducing vaccine-enhanced respiratory disease after vaccination of young children with formalin-inactivated rsv (fi-rsv) in alum formulation. here, we investigated alum adjuvant effects on protection and disease after fi-rsv immunization with or without alum in comparison with live rsv reinfections. despite viral clearance, live rsv reinfections caused weight loss and substantial pulmonary inflammation probably due to high levels of rsv specifi ...201526468884
tangeretin from citrus reticulate inhibits respiratory syncytial virus replication and associated inflammation in vivo.human respiratory syncytial virus (rsv) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. our previous study showed that tangeretin from citrus reticulate possessed potent in vitro anti-rsv effects comparable to that of ribavirin. therefore, in this study, we investigated the in vivo anti-rsv activity of tangeretin in 3-week-old male balb/c mice. a plaque reduction assay and fluorescence quantitative polymerase chain reaction (fq-pcr) showed that tangere ...201526468759
respiratory syncytial virus attachment glycoprotein contribution to infection depends on the specific fusion protein.human respiratory syncytial virus (rsv) is an important pathogen causing acute lower respiratory tract disease in children. the rsv attachment glycoprotein (g) is not required for infection, as g-null rsv replicates efficiently in several cell lines. our laboratory previously reported that the viral fusion (f) protein is a determinant of strain-dependent pathogenesis. here, we hypothesized that virus dependence on g is determined by the strain specificity of f. we generated recombinant viruses e ...201526468535
multiplex sybr green real-time pcr assay for detection of respiratory viruses.it is often difficult for a physician to distinguish between viral and bacterial causes of respiratory infections and this may result in overuse of antibiotics. in many cases of community-acquired respiratory infections, clinicians treat patients empirically. the development of molecular methods for direct detection of viruses has been progressed recently.201526468358
prefusion f-specific antibodies determine the magnitude of rsv neutralizing activity in human sera.respiratory syncytial virus (rsv) is estimated to claim more lives among infants <1 year old than any other single pathogen, except malaria, and poses a substantial global health burden. viral entry is mediated by a type i fusion glycoprotein (f) that transitions from a metastable prefusion (pre-f) to a stable postfusion (post-f) trimer. a highly neutralization-sensitive epitope, antigenic site ø, is found only on pre-f. we determined what fraction of neutralizing (nt) activity in human sera is ...201526468324
neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease.human respiratory syncytial virus (rsv) is the most important cause of severe lower respiratory tract disease (lrtd) in young children worldwide. extensive neutrophil accumulation in the lungs and occlusion of small airways by dna-rich mucus plugs are characteristic features of severe rsv-lrtd. activated neutrophils can release neutrophil extracellular traps (nets), extracellular networks of dna covered with antimicrobial proteins, as part of the first-line defence against pathogens. nets can tr ...201626468056
viral etiology of acute respiratory tract infections in hospitalized children and adults in shandong province, china.the dominant viral etiologies responsible for acute respiratory infections (aris) are poorly understood, particularly among hospitalized patients. improved etiological insight is needed to improve clinical management and prevention of aris.201526467854
fc receptors and their influence on efficacy of therapeutic antibodies for treatment of viral diseases.the lack of vaccines against several important viral diseases necessitates the development of therapeutics to save lives and control epidemics. in recent years, therapeutic antibodies have received considerable attention due to their good safety profiles and clinical success when used against viruses such as respiratory syncytial virus, ebola virus and hendra virus. the binding affinity of these antibodies can directly impact their therapeutic efficacy. however, we and others have also demonstra ...201526466016
human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in beijing, china.hpyv6 is a novel human polyomavirus (hpyv), and neither its natural history nor its prevalence in human disease is well known. therefore, the epidemiology and phylogenetic status of hpyv6 must be systematically characterized.201526463646
cross-immunity between strains explains the dynamical pattern of paramyxoviruses.viral respiratory tract diseases pose serious public health problems. our ability to predict and thus, be able to prepare for outbreaks is strained by the complex factors driving the prevalence and severity of these diseases. the abundance of diseases and transmission dynamics of strains are not only affected by external factors, such as weather, but also driven by interactions among viruses mediated by human behavior and immunity. to untangle the complex out-of-phase annual and biennial pattern ...201526460003
risk of respiratory syncytial virus infection in preterm infants: reviewing the need for prevention.premature infants are at substantial risk for a spectrum of morbidities that are gestational age dependent. respiratory syncytial virus (rsv) infection is most common in the first two years of life with the highest burden in children aged <6 months. preterm infants ≤35 weeks' gestation are handicapped by incomplete immunological and pulmonary maturation and immature premorbid lung function with the added risk of bronchopulmonary dysplasia. superimposed rsv infection incites marked neutrophilic a ...201526457970
novel therapies and vaccines against the human respiratory syncytial virus.human respiratory syncytial virus (hrsv) is the leading cause of acute lower respiratory tract infections worldwide in infants, as well as an important pathogen affecting the elderly and immunocompromised individuals. despite more than a half a century of research, no licensed vaccines are available and only palivizumab has been approved to use in humans, mostly recommended or limited to high risk infants. therefore, novel therapeutic and preventive drugs need to be developed to fight this major ...201526457559
aln-rsv01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients.respiratory syncytial virus (rsv) infection in lung transplant (ltx) patients is associated with an increased incidence of bronchiolitis obliterans syndrome (bos). aln-rsv01 is a small interfering rna targeting rsv replication that was shown in an earlier phase 2a trial to be safe and to reduce the incidence of bos when compared with placebo.201626452996
contribution of fcγ receptors to human respiratory syncytial virus pathogenesis and the impairment of t-cell activation by dendritic cells.human respiratory syncytial virus (hrsv) is the leading cause of infant hospitalization related to respiratory disease. infection with hrsv produces abundant infiltration of immune cells into the airways, which combined with an exacerbated pro-inflammatory immune response can lead to significant damage to the lungs. human rsv re-infection is extremely frequent, suggesting that this virus may have evolved molecular mechanisms that interfere with host adaptive immunity. infection with hrsv can be ...201626451966
assessing uncertainty in a2 respiratory syncytial virus viral dynamics.respiratory syncytial virus (rsv) is the most common cause of bronchiolitis and pneumonia in children younger than 1 year of age in the united states. moreover, rsv is being recognized more often as a significant cause of respiratory illness in older adults. although rsv has been studied both clinically and in vitro, a quantitative understanding of the infection dynamics is still lacking. in this paper, we study the effect of uncertainty in the main parameters of a viral kinetics model of rsv. w ...201526451163
crawling with virus: translational insights from a neonatal mouse model on the pathogenesis of respiratory syncytial virus in infants.the infant immune response to respiratory syncytial virus (rsv) remains incompletely understood. here we review the use of a neonatal mouse model of rsv infection to mimic severe infection in human infants. we describe numerous age-specific responses, organized by cell type, observed in rsv-infected neonatal mice and draw comparisons (when possible) to human infants.201526446604
aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: a systematic review and meta-analysis.acute lower respiratory infection (alri) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of alri is unclear. we aimed to quantify the absolute effects of these viral exposures.201526445672
biophysical characterization of g protein ectodomain of group b human respiratory syncytial virus from e. coli.human respiratory syncytial virus (hrsv) is an important pathogen of acute respiratory tract infection. the g protein of hrsv is a transmembrane glycoprotein that is a neutralizing antigen and is thus a vaccine candidate. in this study, synthetic codon optimized ectodomain g protein [g(δtm)] of ba genotype of group b hrsv was cloned, expressed, and characterized using biophysical techniques. the molar absorption coefficient and mean residue ellipticity at 222 nm ([θ]222) of g (δtm) was found to ...201626444871
emerging roles of trna-derived fragments in viral infections: the case of respiratory syncytial virus. 201526442802
effects of vaccination against respiratory pathogens on feed intake, metabolic, and inflammatory responses in beef heifers.the objective of this study was to evaluate intake, metabolic, inflammatory, and acute-phase responses in beef heifers vaccinated against pathogens that cause bovine respiratory disease (brd). eighteen weaned angus heifers (initial bw 257 ± 3 kg; initial age 245 ± 2 d) were ranked by bw and allocated to 2 groups, which were assigned to 2 experiments of 7 d and the following treatments on d 1 of each experiment: 1) revaccinated against infectious bovine rhinotracheitis virus, parainfluenza-3 viru ...201526440344
generation and characterization of alx-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection.respiratory syncytial virus (rsv) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. its fusion (f) protein is critical for virus infection. it is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe rsv disease. alx-0171 is a trimeric nanobody that binds the antigenic site ii of rsv f protein with subnanomolar affinity. alx-0171 ...201526438495
alveolar macrophages support interferon gamma-mediated viral clearance in rsv-infected neonatal mice.poor interferon gamma (ifnγ) production during respiratory syncytial virus (rsv) is associated with prolonged viral clearance and increased disease severity in neonatal mice and humans. we previously showed that intra-nasal delivery of ifnγ significantly enhances rsv clearance from neonatal lungs prior to observed t-lymphocyte recruitment or activation, suggesting an innate immune mechanism of viral clearance. we further showed that alveolar macrophages dominate the rsv-infected neonatal airways ...201526438053
respiratory syncytial virus induces phosphorylation of mtor at ser2448 in cd8 t cells from nasal washes of infected infants.respiratory syncytial virus (rsv)-specific cd8(+) t cell responses do not protect against reinfection. activation of mammalian target of rapamycin (mtor) impairs memory cd8(+) t cell differentiation. our hypothesis was that rsv inhibits the formation of cd8(+) t cells memory responses through mtor activation. to explore this, human and mouse t cells were used. rsv induced mtor phosphorylation at ser2448 in cd8 t cells. mtor activation by rsv was completely inhibited using rapamycin. rsv-infected ...201626437614
spatial clusters of child lower respiratory illnesses associated with community-level risk factors.identifying geographic areas with increased incidence of disease may elucidate community-level risk factors for intervention development. lower respiratory illnesses (lris) are the leading cause of death in children and are associated with other morbidities. we assessed geographic clustering of lris and evaluated if these spatial patterns and associated risk factors differed by phenotype. participants enrolled at birth in the tucson children's respiratory study were followed through age three fo ...201626436763
preventing hospitalizations for respiratory syncytial virus infection.respiratory syncytial virus infection is the leading cause of lower respiratory tract infections in young children. palivizumab has minimal impact on rsv hospitilization rates as it is only practical to offer it to the highest risk groups. the present statement reviews the published literature and provides updated recommendations regarding palivizumab use in children in canada.201726435673
development of next-generation respiratory virus vaccines through targeted modifications to viral immunomodulatory genes.vaccines represent one of the greatest contributions of the scientific community to global health. yet, many pathogens remain either unchallenged or inadequately hindered by commercially available vaccines. respiratory viruses pose distinct and difficult challenges due to their ability to rapidly spread, adapt, and modify the host immune response. considerable research has been directed to understand the role of respiratory virus immunomodulatory proteins and how they influence the host immune r ...201526434947
an epitope-specific respiratory syncytial virus vaccine based on an antibody scaffold.respiratory syncytial virus (rsv) is a leading cause of lower respiratory tract infections in children. we have generated an epitope-specific rsv vaccine by grafting a neutralizing epitope (f-epitope) in its native conformation into an immunoglobulin scaffold. the resulting antibody fusion exhibited strong binding affinity to motavizumab, an rsv neutralizing antibody, and effectively induced potent neutralizing antibodies in mice. this work illustrates the potential of the immunoglobulin molecul ...201526434555
influenza and respiratory syncytial viruses: efficacy of different diagnostic assays.to determine the efficacy of cell culture, immunoflourescence assay (ifa) and real time polymerase chain reaction (rrt-pcr) in relation to diagnosis of influenza and respiratory syncytial virus (rsv).201726430404
adenovirus infection in children with acute lower respiratory tract infections in beijing, china, 2007 to 2012.human adenoviruses (hadv) play a significant role in pediatric respiratory tract infections. to date, over 60 types of hadv have been identified. here, hadv types are characterized in children in the beijing area with acute lower respiratory tract infections (alrtis) and the clinical features and laboratory findings of hospitalized hadv-infected cases are described.201526429778
the seroprevalence of some pathogen specific igm in children with acute respiratory tract infections in guangzhou region, 2011 - 2012.acute respiratory tract infections (artis) are the leading cause of morbidity and death in children < 5 years worldwide. the aim of this study is to analyze the seroprevalence of nine pathogen specific igms in children with artis with respect to gender, age, and seasonality in the guangzhou region.201526427134
pro-inflammatory cytokines in nasopharyngeal aspirate from hospitalized children with respiratory syncytial virus infection with or without rhinovirus bronchiolitis, and use of the cytokines as predictors of illness severity.respiratory syncytial virus (rsv) and human rhinovirus (hrv) respiratory infection in children induce production of inflammatory interleukins (ils) in the respiratory epithelium. as il(s) determine the severity of illness, the purpose of this study was to identify the pro-inflammatory il(s) that could be predictor(s) of clinical severity. one hundred and fifteen patients <2 years old with bronchiolitis due to rsv and /or hrv and 38 controls were selected from a hospital and an outpatient clinic. ...201526426613
induction and antagonism of antiviral responses in respiratory syncytial virus-infected pediatric airway epithelium.airway epithelium is the primary target of many respiratory viruses. however, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. to address this, we developed a model of respiratory syncytial virus (rsv) infection based on well-differentiated pediatric primary bronchial epithelial cell cultures (wd-pbecs) that mimics hallmarks of rsv disease in infants. rsv is the most important respiratory viral pathogen in young infants worldwide. we found th ...201526423940
genetic diversity and evolutionary insights of respiratory syncytial virus a on1 genotype: global and local transmission dynamics.human respiratory syncytial virus (rsv) a on1 genotype, first detected in 2010 in ontario, canada, has been documented in 21 countries to date. this study investigated persistence and transmission dynamics of on1 by grouping 406 randomly selected rsv-positive specimens submitted to public health ontario from august 2011 to august 2012; rsv-a-positive specimens were genotyped. we identified 370 rsv-a (181 na1, 135 na2, 51 on1 3 ga5) and 36 rsv-b positive specimens. we aligned time-stamped second ...201526420660
emergency department syndromic surveillance providing early warning of seasonal respiratory activity in england.seasonal respiratory infections place an increased burden on health services annually. we used a sentinel emergency department syndromic surveillance system to understand the factors driving respiratory attendances at emergency departments (eds) in england. trends in different respiratory indicators were observed to peak at different points during winter, with further variation observed in the distribution of attendances by age. multiple linear regression analysis revealed acute respiratory infe ...201626415918
lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics.respiratory syncytial virus (rsv) is a major worldwide cause of morbidity and mortality in children under five years of age. evidence-based management guidelines suggest that there is no effective treatment for rsv lower respiratory tract infection (lrti) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. however, rsv treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. maternal ...201526411809
molecular evolution of the hypervariable region of the attachment glycoprotein gene in human respiratory syncytial virus subgroup b genotypes ba9 and ba10.we studied the molecular evolution of the c-terminal 3rd hypervariable region in the attachment glycoprotein gene of human respiratory syncytial virus subgroup b (hrsv-b) genotypes ba9 and ba10. we performed time-scaled phylogenetic analyses using bayesian markov chain monte carlo methods. we also performed a genetic distance analysis (p-distance analysis), positive and negative selection analyses, and a bayesian skyline plot (bsp) analysis. we found that genotype ba9 diverged from the common an ...201526408340
circulation of a novel human respiratory syncytial virus group b genotype during the 2014-2015 season in catalonia (spain).human respiratory syncytial virus (hrsv) is one of the most common viral aetiological agents in the youngest population. in the present study a novel hrsv-b ba genotype is first described based on the phylogenetic analysis of the coding hypervariable region 2 sequences of g protein from strains detected during the 2014-2015 season. among all strains detected in the last season, 44% belonged to this new genotype. therefore, it highlights the importance of a continuous hrsv surveillance to monitor ...201626408279
direct whole-genome deep-sequencing of human respiratory syncytial virus a and b from vietnamese children identifies distinct patterns of inter- and intra-host evolution.human respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infections in children ,2 years of age. little is known about rsv intra-host genetic diversity over the course of infection or about the immune pressures that drive rsv molecular evolution. we performed whole-genome deep-sequencing on 53 rsv-positive samples (37 rsv subgroup a and 16 rsv subgroup b) collected from the upper airways of hospitalized children in southern vietnam over two consecutive seasons. rsv a ...201526407694
new epidemiological and clinical signatures of 18 pathogens from respiratory tract infections based on a 5-year study.respiratory tract infections (rtis) are a heavy burden on society. however, due to the complex etiology of rtis, the clinical diagnosis, treatment, and prevention of these infections remain challenging, especially in developing countries.201526406339
development of spr biosensor for simultaneous detection of multiplex respiratory viruses.a surface plasmon resonance (spr)-based biosensor was developed for specific detection of nine common respiratory virus, including influenza a and influenza b, h1n1, respiratory syncytial virus (rsv), parainfluenza virus 1-3 (piv1, 2, 3), adenovirus, and severe acute respiratory syndrome coronavirus (sars). the spr biosensor was developed by immobilizing nine respiratory virus-specific oligonucleotides in an spr chip. to increase the biosensor sensitivity, biotin was used to label the pcr primer ...201526406000
predictors of severe disease in a hospitalized population of children with acute viral lower respiratory tract infections.although predictors of severe viral acute lower respiratory infections (alris) in children have been reported, there have been few research studies performed in low- and middle-income countries (lmic). the aim of the present study was to determine predictors of disease severity in a population of colombian children <5 years of age with alri. in a prospective cohort study, we determined independent predictors of severe alri in a hospitalized population of children under 5 years old with alri duri ...201626403374
viral respiratory tract infections in adult patients attending outpatient and emergency departments, taiwan, 2012-2013: a pcr/electrospray ionization mass spectrometry study.viral etiologies of respiratory tract infections (rtis) have been less studied in adult than in pediatric populations. furthermore, the ability of pcr/electrospray ionization mass spectrometry (pcr/esi-ms) to detect enteroviruses and rhinoviruses in respiratory samples has not been well evaluated. we sought to use pcr/esi-ms to comprehensively investigate the viral epidemiology of adult rtis, including testing for rhinoviruses and enteroviruses. nasopharyngeal or throat swabs from 267 adults wit ...201526402811
perceived risk of severe respiratory syncytial virus disease and immunoprophylaxis use among us pediatric specialists.this study was conducted to assess the perception of us pediatric specialists of respiratory syncytial virus (rsv) disease risk and determine their clinical practices regarding immunoprophylaxis for high-risk children. separate surveys were sent to neonatologists, pediatricians, pediatric pulmonologists, and pediatric cardiologists. data were collected using structured questions requiring quantitative responses. most neonatologists and pediatricians (>82.7%) reported a high clinical need for rsv ...201626400767
risk factors for hospitalization for respiratory syncytial virus infection: a population-based cohort study of danish children.the aim of this study is to identify the risk factors for hospitalization for respiratory syncytial virus (rsv) infection in danish children.201626398871
communicable diseases prioritized according to their public health relevance, sweden, 2013.to establish strategic priorities for the public health agency of sweden we prioritized pathogens according to their public health relevance in sweden in order to guide resource allocation. we then compared the outcome to ongoing surveillance. we used a modified prioritization method developed at the robert koch institute in germany. in a delphi process experts scored pathogens according to ten variables. we ranked the pathogens according to the total score and divided them into four priority gr ...201526397699
vaccine induced herd immunity for control of respiratory syncytial virus disease in a low-income country setting.respiratory syncytial virus (rsv) is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently rsv is the most important viral cause of respiratory morbidity and mortality in young children. development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. vaccine development for young infant ...201526390032
viral etiology in infants hospitalized for acute bronchiolitis.acute bronchiolitis is predominantly a viral disease. respiratory syncytial virus is the most common agent, but other newly identified viruses have also been considered as causes. the aim of the present study is to determine the respiratory viruses causing acute bronchiolitis in hospitalized infants. infants younger than 2 years of age who were hospitalized for acute viral bronchiolitis in a children's hospital between november 2011 and may 2012 were evaluated for the presence of viruses as etio ...201526388588
toward antiviral therapy/prophylaxis for rhinovirus-induced exacerbations of chronic obstructive pulmonary disease: challenges, opportunities, and strategies.chronic obstructive pulmonary disease (copd) is a life-threatening lung illness characterized by persistent and progressive airflow limitation. exacerbations of copd contribute to the severity of this pathology and accelerate disease progression. to date, pharmacological treatment of both stable copd patients and patients experiencing exacerbations is mainly symptomatic with bronchodilators and steroids as the mainstay of therapy. bacteria trigger such exacerbations in a number of cases; hence, ...201526388447
heliox inhalation therapy for bronchiolitis in infants.bronchiolitis is the leading cause of hospitalisation among infants in high-income countries. acute viral bronchiolitis is associated with airway obstruction and turbulent gas flow. heliox, a mixture of oxygen and the inert gas helium, may improve gas flow through high-resistance airways and decrease the work of breathing. in this review, we selected trials that objectively assessed the effect of the addition of heliox to standard medical care for acute bronchiolitis.201526384333
predictors of hospitalization for lower respiratory tract infection in children aged <2 years in the province of quebec, canada.young age, adverse environmental conditions and infectious agents are established risk factors of lower respiratory tract infection (lrti), whereas pneumococcal conjugate vaccines may be protective. to explore their relative role as predictors of hospitalizations under the continental climate prevailing in the province of quebec, canada, an ecological study was performed. records with a main diagnosis of lrti in children born during 2007-2010 and observed up to their second-year anniversary were ...201626381086
serological detection of infection dynamics for respiratory viruses among dairy calves.the aim of this study is to reveal infection dynamics of bovine respiratory syncytial virus (brsv), bovine parainfluenza virus type 3 (pi-3), bovine herpesvirus 1 (bhv-1), bovine viral diarrhea virus (bvdv), bovine adenovirus type 3 (bav-3) and bovine coronavirus (bcov), which are important viral pathogens of respiratory disease complex in ruminants. through such an analysis, the regression period of maternally derived antibodies and optimum vaccination time in calves can be recommended. a total ...201526380946
therapeutic immunoglobulin selected for high antibody titer to rsv also contains high antibody titers to other respiratory viruses.specific antibodies against infections most relevant to patients with primary immunodeficiency diseases are not routinely evaluated in commercial polyclonal immunoglobulin preparations. a polyclonal immunoglobulin prepared from plasma of donors having high neutralizing antibody titers to respiratory syncytial virus (rsv) was studied for the presence of antibody titers against seven additional respiratory viruses. while donors were not selected for antibody titers other than against rsv, the immu ...201526379667
respiratory syncytial virus preterm (32-36 completed weeks of gestation) risk estimation measure for rsv hospitalization in ireland: a prospective study.in several countries, respiratory syncytial virus prophylaxis is offered to late preterm infants who are at escalated risk of respiratory syncytial virus hospitalization (rsvh). however, targeted prophylaxis should be informed by country-specific data. this study, which uniquely includes 36 weeks of gestational age (ga) infants, aims to establish the risk factors for rsvh in 32-36 weeks of ga infants in ireland.201626379160
regulation of viral rna synthesis by the v protein of parainfluenza virus 5.paramyxoviruses include many important animal and human pathogens. the genome of parainfluenza virus 5 (piv5), a prototypical paramyxovirus, encodes a v protein that inhibits viral rna synthesis. in this work, the mechanism of inhibition was investigated. using mutational analysis and a minigenome system, we identified regions in the n and c termini of the v protein that inhibit viral rna synthesis: one at the very n terminus of v and the second at the c terminus of v. furthermore, we determined ...201526378167
mumps virus is released from the apical surface of polarized epithelial cells, and the release is facilitated by a rab11-mediated transport system.mumps virus (muv) is an airborne virus that causes a systemic infection in patients. in vivo, the epithelium is a major replication site of muv, and thus, the mode of muv infection of epithelial cells is a subject of interest. our data in the present study showed that muv entered polarized epithelial cells via both the apical and basolateral surfaces, while progeny viruses were predominantly released from the apical surface. in polarized cells, intracellular transport of viral ribonucleoprotein ...201526378159
understanding the association of human rhinovirus with asthma.human rhinoviruses are ubiquitous seasonal pathogens. they have known associations with first onset of wheezing illnesses in children and with asthma exacerbations in patients of all ages. it is not yet certain whether human rhinoviruses play a direct role in the pathogenesis of asthma by activating deleterious inflammatory responses or if they only serve as a catalyst to accelerate the disease in genetically predisposed individuals. there have been previously demonstrated reductions in the deve ...201526376925
rapid next-generation sequencing of dengue, ev-a71 and rsv-a viruses.accurate characterisation of viral strains constitutes a crucial objective for the management of modern virus collections. next-generation sequencing (ngs) provides technical solution for fast and cost-effective full genome sequencing. here, we report protocols for rapid full-genome characterisation of rna viruses of medical importance: dengue virus, enterovirus a71 and respiratory syncytial virus a, based on a specific amplification step followed by ngs-sequencing. a subset of full-length genom ...201526376168
clinical and laboratory characteristics of viral lower respiratory tract infections in preschool children.viral lower respiratory tract infections are the leading cause of hospitalizations in preschool children. clinical pictures of different viral causes are not well characterized. the aim of this study was to establish the differences in clinical and laboratory characteristics between the different viral causes of lower respiratory tract infections in preschool children.201526373742
proteomic profiling of a respiratory syncytial virus-infected rat pneumonia model.respiratory syncytial virus (rsv) is a major cause of lower respiratory tract disease in pediatric patients. our goal was to obtain a detailed understanding of the molecular pathogenesis of rsv infections by studying the protein expression profiles in rats with pneumonia. first, we successfully established a pneumonia rat model by intranasally injecting rsv. the differentially expressed proteins in lung tissues of rsv-infected rats compared with those of the controls were analyzed by using 2-dim ...201626370426
early occurrence of influenza a epidemics coincided with changes in occurrence of other respiratory virus infections.viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear.201626369646
treatment with novel rsv ig ri-002 controls viral replication and reduces pulmonary damage in immunocompromised sigmodon hispidus.respiratory syncytial virus (rsv) is a significant cause of bronchiolitis and pneumonia in several high health risk populations, including infants, elderly and immunocompromised individuals. mortality in hematopoietic stem cell transplant recipients with lower respiratory tract rsv infection can exceed 80%. it has been shown that rsv replication in immunosuppressed individuals is significantly prolonged, but the contribution of pulmonary damage, if any, to the pathogenesis of rsv disease in this ...201626367224
two cases of pneumatoceles in mechanically ventilated infants.pulmonary pneumatocele is a thin-walled, gas-filled space within the lung that usually occurs in association with bacterial pneumonia and is usually transient. the majority of pneumatoceles resolve spontaneously without active intervention, but in some cases they might lead to pneumothorax with subsequent hemodynamic instability. we report two cases presented to the pediatric intensive care unit at the royal hospital, oman with pneumatoceles. the first was a 14-day-old baby who underwent surgica ...201526366266
outcome of the respiratory syncytial virus related acute lower respiratory tract infection among hospitalized newborns: a prospective multicenter study.to determine the incidence and outcomes of respiratory syncytial virus (rsv)-related acute lower respiratory tract infection (alri) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (nicus).201626365531
temporal trends and factors associated with pediatric hospitalizations with respiratory infection.asthma is the leading cause of emergency room visits in children, and those with asthma tend to suffer from more severe consequences of respiratory tract infections. the aims of this study were among children who required hospitalization, compare differences between those admitted with or without respiratory infection, describe changes in yearly proportion of asthma among the children admitted with a respiratory infection in new york city from 2006 to 2012 and ascertain how asthma affected the a ...201626364908
complete genome sequence of human respiratory syncytial virus from shanghai, china.we report here the complete genome sequence of human respiratory syncytial virus isolated from an outpatient child with fever and respiratory symptoms in shanghai, china, in 2014. phylogenetic analysis showed that the full-length respiratory syncytial virus (rsv) genome sequence belongs to human rsv (hrsv) group a.201526358591
new vaccines for the world's poorest people.the 2000 millennium development goals helped stimulate the development of life-saving childhood vaccines for pneumococcal and rotavirus infections while greatly expanding coverage of existing vaccines. however, there remains an urgent need to develop new vaccines for hiv/aids, malaria, and tuberculosis, as well as for respiratory syncytial virus and those chronic and debilitating (mostly parasitic) infections known as neglected tropical diseases (ntds). the ntds represent the most common disease ...201626356803
virus-like particle vaccine containing the f protein of respiratory syncytial virus confers protection without pulmonary disease by modulating specific subsets of dendritic cells and effector t cells.there is no licensed vaccine against respiratory syncytial virus (rsv) since the failure of formalin-inactivated rsv (fi-rsv) due to its vaccine-enhanced disease. we investigated immune correlates conferring protection without causing disease after intranasal immunization with virus-like particle vaccine containing the rsv fusion protein (f vlp) in comparison to fi-rsv and live rsv. upon rsv challenge, fi-rsv immune mice showed severe weight loss, eosinophilia, and histopathology, and rsv reinfe ...201526355098
successive respiratory syncytial virus epidemics in local populations arise from multiple variant introductions, providing insights into virus persistence.respiratory syncytial virus (rsv) is a global respiratory pathogen of humans, with infection occurring characteristically as recurrent seasonal epidemics. unlike influenza viruses, little attention has been paid to the mechanism underlying worldwide spread and persistence of rsv and how this may be discerned through an improved understanding of the introduction and persistence of rsv in local communities. we analyzed 651 attachment (g) glycoprotein nucleotide sequences of rsv b collected over 11 ...201526355091
diagnostic accuracy of rapid antigen detection tests for respiratory syncytial virus infection: systematic review and meta-analysis.respiratory syncytial virus (rsv) rapid antigen detection tests (radt) are extensively used in clinical laboratories. we performed a systematic review and meta-analysis to evaluate the accuracy of radts for diagnosis of rsv infection and to determine factors associated with accuracy estimates. we searched embase and pubmed for diagnostic-accuracy studies of commercialized rsv radts. studies reporting sensitivity and specificity data compared to a reference standard (reverse transcriptase pcr [rt ...201526354816
use of genetically-encoded calcium indicators for live cell calcium imaging and localization in virus-infected cells.calcium signaling is a ubiquitous and versatile process involved in nearly every cellular process, and exploitation of host calcium signals is a common strategy used by viruses to facilitate replication and cause disease. small molecule fluorescent calcium dyes have been used by many to examine changes in host cell calcium signaling and calcium channel activation during virus infections, but disadvantages of these dyes, including poor loading and poor long-term retention, complicate analysis of ...201526344758
vitamin d levels are unrelated to the severity of respiratory syncytial virus bronchiolitis among hospitalized infants.vitamin d deficiency at birth has been reported as a risk factor for respiratory syncytial virus (rsv) lower respiratory tract infection during the first year of life. limited data are available on whether an infant's vitamin d status is associated with the severity of acute rsv bronchiolitis.201526336601
immunostimulatory defective viral genomes from respiratory syncytial virus promote a strong innate antiviral response during infection in mice and humans.human respiratory syncytial virus (rsv) is a major cause of severe respiratory illness in children and susceptible adults. rsv blocks the development of the innate antiviral immune response and can grow to high titers in the respiratory tract. here we demonstrate that immunostimulatory defective viral genomes (idvgs) that are naturally generated during rsv replication are strong inducers of the innate antiviral response to rsv in mice and humans. in mice, rsv idvgs stimulated the expression of a ...201526336095
use of qualitative integrative cycler pcr (qicpcr) to identify optimal therapeutic dosing time-points in a respiratory syncytial virus human viral challenge model (hvcm).retroscreen (hvivo) have developed an rsv human viral challenge model (hvcm) for testing the efficacy of novel antiviral therapies by monitoring changes in viral load and symptoms. the integrated cycler technology and simplexa™ kits (focus diagnostics) currently provide fast, qualitative and sensitive diagnostic testing in hospitals and other healthcare facilities for patients with well-established respiratory illness. we have developed a novel use of qualitative integrated cycler pcr (qicpcr) t ...201526335961
maternal transfer of rsv immunity in cotton rats vaccinated during pregnancy.respiratory syncytial virus (rsv) is the leading cause of pneumonia and bronchiolitis in infants, resulting in significant morbidity and mortality worldwide. there is currently no rsv vaccine. although maternal serum antibodies against rsv are efficiently transferred through placenta protecting human infants from rsv-induced disease, this protection is short-lived and the methods for extending and augmenting protection are not known. the objective of this study was to develop an animal model of ...201526335771
detection of 12 respiratory viruses by duplex real time pcr assays in respiratory samples.different viruses can be responsible for similar clinical manifestations of respiratory infections. thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. in this study, 6 duplex real-time pcr assays, using evagreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza a and b viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human ...201526334289
a highly stable prefusion rsv f vaccine derived from structural analysis of the fusion mechanism.respiratory syncytial virus (rsv) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. recently, a promising vaccine antigen based on the rsv fusion protein (rsv f) stabilized in the native prefusion conformation has been described. here we report alternative strategies to arrest rsv f in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion pept ...201526333350
viral co-infections in pediatric patients hospitalized with lower tract acute respiratory infections.molecular techniques can often reveal a broader range of pathogens in respiratory infections. we aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (lt-ari), using molecular techniques.201526332375
gs-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein.gs-5806 is a small-molecule inhibitor of human respiratory syncytial virus fusion protein-mediated viral entry. during viral entry, the fusion protein undergoes major conformational changes, resulting in fusion of the viral envelope with the host cell membrane. this process is reproduced in vitro using a purified, truncated respiratory syncytial virus (rsv) fusion protein. gs-5806 blocked these conformational changes, suggesting a possible mechanism for antiviral activity.201526324264
respiratory virus modulation of host nucleocytoplasmic transport; target for therapeutic intervention?the respiratory diseases caused by rhinovirus, respiratory syncytial virus, and influenza virus represent a large social and financial burden on healthcare worldwide. although all three viruses have distinctly unique properties in terms of infection and replication, they share the ability to exploit/manipulate the host-cell nucleocytoplasmic transport system in order to replicate effectively and efficiently. this review outlines the various ways in which infection by these viruses impacts on the ...201526322040
antiviral activity of an aqueous extract derived from aloe arborescens mill. against a broad panel of viruses causing infections of the upper respiratory tract.a number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. but these therapies are very often of limited efficacy or have severe side effects. therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin.201526321740
recombinant low-seroprevalent adenoviral vectors ad26 and ad35 expressing the respiratory syncytial virus (rsv) fusion protein induce protective immunity against rsv infection in cotton rats.rsv is an important cause of lower respiratory tract infections in children, the elderly and in those with underlying medical conditions. although the high disease burden indicates an urgent need for a vaccine against rsv, no licensed rsv vaccine is currently available. we developed an rsv vaccine candidate based on the low-seroprevalent human adenovirus serotypes 26 and 35 (ad26 and ad35) encoding the rsv fusion (f) gene. single immunization of mice with either one of these vectors induced high ...201526319741
protein conformation in a vaccine matters. 201526318167
high-frequency oscillatory ventilation in pediatric acute lung injury: a multicenter international experience.we aim to describe current clinical practice, the past decade of experience and factors related to improved outcomes for pediatric patients receiving high-frequency oscillatory ventilation. we have also modeled predictive factors that could help stratify mortality risk and guide future high-frequency oscillatory ventilation practice.201526317570
path to impact: a report from the bill and melinda gates foundation convening on maternal immunization in resource-limited settings; berlin - january 29-30, 2015.global initiatives such as the millennium development goals have led to major improvements in the health of women and children, and significant reductions in childhood mortality. worldwide, maternal mortality has decreased by 45% and under-five mortality has fallen by over 50% over the past two decades [1]. however, improvements have not been achieved evenly across all ages; since 1990, under-five mortality has declined by ∼5% annually, but the average decrease in neonatal mortality is only ∼3% ...201526314626
natural history and epidemiology of respiratory syncytial virus infection in the middle east: hospital surveillance for children under age two in jordan.respiratory syncytial virus (rsv) is the leading cause of bronchiolitis and viral pneumonia in infants and young children worldwide. in the middle east and arab countries, the burden of rsv-associated hospitalizations is not well characterized. we sought to determine the burden and clinical/epidemiological characteristics of rsv hospitalization in young children in amman, jordan. we investigated risk factors for severity including vitamin d levels.201526314623
[epidemiologic characteristics and the relationship with disease severity of respiratory syncytial virus genotypes from children with lower respiratory tract infection in the southern zhejiang province].to investigate the epidemiological characteristics of respiratory syncytial virus (rsv) subtypes and genotypes in southern zhejiang province, and to determine whether rsv genotypes are correlated with the disease severity of lower respiratory tract infection (lrti).201526310648
acute and chronic airway disease after human respiratory syncytial virus infection in cotton rats (sigmodon hispidus).infection with respiratory syncytial virus (rsv) generally presents as a mild, upper airway disease in human patients but may cause severe lower airway disease in the very young and very old. progress toward understanding the mechanisms of rsv pathogenesis has been hampered by a lack of relevant rodent models. mice, the species most commonly used in rsv research, are resistant to upper respiratory infection and do not recapitulate the pattern of virus spread in the human host. to address the nee ...201526310461
the effect of dietary bovine colostrum on respiratory syncytial virus infection and immune responses following the infection in the mouse.human respiratory syncytial virus (hrsv) is the most common cause of respiratory tract infection among young children because of immature t cell immunity of them against hrsv. cd8 t cells play a pivotal role in clearing hrsv and preventing subsequent infection. we examined the effects of dietary bovine colostrum on virus infection and cd8 t cell responses following hrsv infection in the mouse model. mice received bovine colostrum for 14 days prior to hrsv challenge, and lung indexes (severity of ...201526310306
intranasal nanoemulsion-based inactivated respiratory syncytial virus vaccines protect against viral challenge in cotton rats.respiratory syncytial virus is a leading cause of bronchiolitis and pneumonia in infants, the elderly and individuals with compromised immune systems. despite decades of research, there is currently no available vaccine for rsv. our group has previously demonstrated that intranasal immunization of mice with rsv inactivated by and adjuvanted with w805ec nanoemulsion elicits robust humoral and cellular immune responses, resulting in protection against rsv infection. this protection was achieved wi ...201526307915
replication-competent influenza virus and respiratory syncytial virus luciferase reporter strains engineered for co-infections identify antiviral compounds in combination screens.myxoviruses such as influenza a virus (iav) and respiratory syncytial virus (rsv) are major human pathogens, mandating the development of novel therapeutics. to establish a high-throughput screening protocol for the simultaneous identification of pathogen- and host-targeted hit candidates against either pathogen or both, we have attempted co-infection of cells with iav and rsv. however, viral replication kinetics were incompatible, rsv signal window was low, and an iav-driven minireplicon report ...201526307636
4ebp1 is dephosphorylated by respiratory syncytial virus infection.respiratory syncytial virus (rsv) requires protein biosynthesis machinery to generate progeny. there is evidence that rsv might alter some translation components since stress granules are formed in their host cells. consistent with these observations, we found that rsv induces dephosphorylation of 4ebp1 (eif4e-binding protein), an important cellular translation factor. our results show no correlation between the 4ebp1 dephosphorylation time and the decrease in the global rate of protein synthesi ...201526305094
detecting respiratory viral rna using expanded genetic alphabets and self-avoiding dna.nucleic acid (na)-targeted tests detect and quantify viral dna and rna (collectively xna) to support epidemiological surveillance and, in individual patients, to guide therapy. they commonly use polymerase chain reaction (pcr) and reverse transcription pcr. although these all have rapid turnaround, they are expensive to run. multiplexing would allow their cost to be spread over multiple targets, but often only with lower sensitivity and accuracy, noise, false positives, and false negatives; thes ...201526299645
elevated il-3 and il-12p40 levels in the lower airway of infants with rsv-induced bronchiolitis correlate with recurrent wheezing.respiratory syncytial virus (rsv) is the first cause of hospitalization due to bronchiolitis in infants. rsv bronchiolitis has been linked to asthma and recurrent wheezing, however the mechanisms behind this association have not been elucidated. here, we evaluated the cytokine and chemokine profiles in the airways in infants with rsv bronchiolitis. nasopharyngeal aspirates (npa) and bronchoalveolar lavage fluids (balf) from infants hospitalized due to rsv bronchiolitis and healthy controls were ...201526299549
blunted inflammatory and mucosal iga responses to pneumonia virus of mice in c57bl/6 neonates are correlated to reduced protective immunity upon re-infection as elderly mice.respiratory syncytial virus is a major cause of bronchiolitis in infants and pneumonia virus of mice (pvm) causes similar disease in mice. the impact of pvm infection in balb/c and c57bl/6 neonates, and upon re-infection as elderly mice, was compared. as previously shown for adult mice, pvm caused more disease in balb/c than in c57bl/6 neonates. after pvm-15 infection balb/c neonates showed higher production of inflammatory mediators, more influx of plasmacytoid dendritic cells and higher ifn-α ...201526298860
respiratory syncytial virus nonstructural proteins 1 and 2 are crucial pathogenic factors that modulate interferon signaling and treg cell distribution in mice.respiratory syncytial virus (rsv) nonstructural (ns) proteins 1 and 2 have multiple functions in suppressing the innate immune response and modulating t helper cell subset differentiation. however, little is known about the roles of ns proteins as independent virulence factors. we investigated the effects of recombinant ns1- and ns2-expressing plasmids on the pathogenesis of murine respiratory tissues and splenetic foxp3+ regulatory t (treg) cell distribution. both ns proteins caused weight loss ...201526298859
assessment of a molecular diagnostic platform for integrated isolation and quantification of mrna in whole blood.implementation of point-of-care tests may facilitate the health management of infectious diseases by reducing the timeframe on pathogen identification and host response measurements, allowing for immediate diagnosis and guided clinical intervention. in this feasibility study, a novel totally integrated and fully automated real-time polymerase chain reaction (pcr) platform (idylla™, biocartis) was assessed to determine the mrna expression levels of multiple genes from 1 ml of whole blood. to this ...201526298058
cx3cr1 is an important surface molecule for respiratory syncytial virus infection in human airway epithelial cells.respiratory syncytial virus (rsv) is a major cause of severe pneumonia and bronchiolitis in infants and young children, and causes disease throughout life. understanding the biology of infection, including virus binding to the cell surface, should help develop antiviral drugs or vaccines. the rsv f and g glycoproteins bind cell surface heparin sulfate proteoglycans (hspgs) through heparin-binding domains. the g protein also has a cx3c chemokine motif which binds to the fractalkine receptor cx3cr ...201526297201
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