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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
emerging roles of trna-derived fragments in viral infections: the case of respiratory syncytial virus. 201526442802
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
genes associated with rsv lower respiratory tract infection and asthma: the application of genetic epidemiological methods to understand causality.infants with respiratory syncytial virus (rsv) lower respiratory tract infections (lris) are at increased risk for childhood asthma. the objectives of this article are to review the genes associated with both rsv lri and asthma, review analytic approaches to assessing shared genetic risk and propose a future perspective on how these approaches can help us to understand the role of infant rsv infection as both an important risk factor for asthma and marker of shared genetic etiology between the t ...201526478738
rsv infections: state of the art.respiratory syncytial virus (rsv) is one of the most common lower respiratory disease in infants and young children worldwide. despite its long history, a safe and effective cure for rsv remains elusive. nonetheless, further understanding of rsv pathogenesis and risk factors have led to advances in prophylaxis and management. the leading risk factor for rsv is premature birth, primarily because fewer protective antibodies are transmitted from the mother to the infant. for full-term born infants, ...201526555808
depletion of regulatory t-cells leads to moderate b-cell antigenicity in respiratory syncytial virus infection.the regulation of the immunopathology of respiratory syncytial virus (rsv) by regulatory t-cells (cd4(+)cd25(+)foxp3(+); tregs) is not understood.201526555647
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
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
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
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
matrix metalloproteinase 9 exerts antiviral activity against respiratory syncytial virus.increased lung levels of matrix metalloproteinase 9 (mmp9) are frequently observed during respiratory syncytial virus (rsv) infection and elevated mmp9 concentrations are associated with severe disease. however little is known of the functional role of mmp9 during lung infection with rsv. to determine whether mmp9 exerted direct antiviral potential, active mmp9 was incubated with rsv, which showed that mmp9 directly prevented rsv infectivity to airway epithelial cells. using knockout mice the ef ...201526284919
neutrophils in respiratory syncytial virus infection: a target for asthma prevention.lower respiratory tract infections by respiratory syncytial virus (rsv) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. neutrophils infiltrate the airways of pediatric patients with rsv-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. however, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. in this review we discuss the bene ...201526277597
use and interpretation of a rapid respiratory syncytial virus antigen detection test among infants hospitalized in a neonatal intensive care unit - wisconsin, march 2015.on march 25, 2015, the wisconsin division of public health was notified of a possible respiratory syncytial virus (rsv) infection outbreak among infants hospitalized in a neonatal intensive care unit (nicu). on march 23, the index patient (neonate a), aged 3 days, had feeding intolerance and apnea. a nasopharyngeal swab specimen collected from neonate a was tested using a single-manufacturer rapid rsv antigen detection test (rradt) at the hospital laboratory; the result was positive. the followi ...201526270063
impact of human rhinovirus types and viral load on the severity of illness in hospitalized children with lower respiratory tract infections.human rhinovirus (hrv) is not only responsible for at least one-half of all common colds but also associated with bronchitis, bronchiolitis, pneumonia and acute asthma exacerbation. however, the impact of different hrv types and viral load on disease severity has not been thoroughly elucidated.201526267309
the role of th17 and treg responses in the pathogenesis of rsv infection.the respiratory syncytial virus (rsv) represents the leading cause of viral bronchiolitis and pneumonia in children worldwide and is associated with high morbidity, hospitalization rate, and significant mortality rates. the immune response elicited by rsv is one of the main factors contributing to the pathogenesis of the disease. two subsets of the cellular immune response, the t helper 17 cell (th17) and the regulatory t-cell (treg), and more particularly the balance between these two subsets, ...201526267154
matrix metalloproteinase-9 mediates rsv infection in vitro and in vivo.respiratory syncytial virus (rsv) is an important human pathogen associated with substantial morbidity and mortality. the present study tested the hypothesis that rsv infection would increase matrix metalloproteinase (mmp)-9 expression, and that mmp-9 inhibition would decrease rsv replication both in vitro and in vivo. rsv a2 infection of human bronchial epithelial cells increased mmp-9 mrna and protein release. cells transfected with sirna against mmp-9 following rsv infection had lower viral t ...201526264019
from bronchiolitis guideline to practice: a critical care perspective.acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. this and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis ...201526261767
in silico structure-based design and synthesis of novel anti-rsv compounds.respiratory syncytial virus (rsv) is the major cause for respiratory tract disease in infants and young children. currently, no licensed vaccine or a selective antiviral drug against rsv infections are available. here, we describe a structure-based drug design approach that led to the synthesis of a novel series of zinc-ejecting compounds active against rsv replication. 30 compounds, sharing a common dithiocarbamate moiety, were designed and prepared to target the zinc finger motif of the m2-1 p ...201526259810
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
respiratory syncytial virus infection inhibits tlr4 signaling via up-regulation of mir-26b.respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract illnesses in infants worldwide. tlr4 signal pathway plays a critical role in regulating immune response against rsv infection. however, the activation of tlr4 in rsv infection is still unclear. in present study, the expression levels of mir-26b and tlr4 mrna were detected in peripheral blood mononuclear cells (pbmcs) of children with or without rsv infected bronchiolitis. the expression levels of tlr4 and its downs ...201526222045
does azithromycin modify viral load during severe respiratory syncytial virus bronchiolitis? 201526215052
enhanced immunogenicity of a respiratory syncytial virus (rsv) f subunit vaccine formulated with the adjuvant gla-se in cynomolgus macaques.respiratory syncytial virus (rsv) causes significant disease in elderly adults, but an effective vaccine is not yet available. we have previously reported that vaccines consisting of engineered respiratory syncytial virus soluble fusion protein (rsv sf) adjuvanted with glucopyranosyl lipid a (gla) in an oil-in-water emulsion (stable emulsion [se]) induce rsv f-specific t and b cell responses in mice and rats that protect from viral challenge. here, we evaluated the immunogenicity of gla-se adjuv ...201526206269
respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and t-cells partially through alveolar macrophages.the mechanisms of protection against respiratory syncytial virus (rsv) are poorly understood. virus-like nanoparticles expressing rsv glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [fg vlps]) have been suggested to be a promising rsv vaccine candidate. to understand the roles of alveolar macrophages (ams) in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated rsv (fi-rsv) or fg vlps were treated with clodronat ...201526203246
[detection of respiratory syncytial virus in the conjunctiva of a child with bronchiolitis caused by this virus]. 201526200035
innate and adaptive cellular phenotypes contributing to pulmonary disease in mice after respiratory syncytial virus immunization and infection.respiratory syncytial virus (rsv) is the major leading cause of infantile viral bronchiolitis. however, cellular phenotypes contributing to the rsv protection and vaccine-enhanced disease remain largely unknown. upon rsv challenge, we analyzed phenotypes and cellularity in the lung of mice that were naïve, immunized with formalin inactivated rsv (fi-rsv), or re-infected with rsv. in comparison with naïve and live rsv re-infected mice, the high levels of eosinophils, neutrophils, plasmacytoid and ...201526196232
healthy late-preterm infants born 33-36+6 weeks gestational age have higher risk for respiratory syncytial virus hospitalization.respiratory syncytial virus (rsv) is a leading cause of hospitalization for children <1year old and is more severe in premature infants.201526186560
low eosinophils during bronchiolitis in infancy are associated with lower risk of adulthood asthma.infant bronchiolitis may be the first manifestation of asthma.201526186154
leptin is oversecreted by respiratory syncytial virus-infected bronchial epithelial cells and regulates th2 and th17 cell differentiation.infection of human bronchial epithelial cells (hbecs) with respiratory syncytial virus (rsv) has been shown to induce a th lymphocyte subset drift, e.g. enhanced differentiation of th2 and th17 subsets, which is a classic characteristic of asthma. however, the molecules responsible for the drift in th subsets remain unknown. this study aims to determine the expression of leptin in rsv-infected hbecs, and its role in th2 and th17 cell differentiation and extracellular regulated kinase (erk) 1/2 p ...201526184438
2'-5'-oligoadenylate synthetase-like protein inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1.2'-5'-oligoadenylate synthetase-like protein (oasl) is an interferon-inducible antiviral protein. here we describe differential inhibitory activities of human oasl and the two mouse oasl homologs against respiratory syncytial virus (rsv) replication. interestingly, nonstructural protein 1 (ns1) of rsv promoted proteasome-dependent degradation of specific oasl isoforms. we conclude that oasl acts as a cellular antiviral protein and that rsv ns1 suppresses this function to evade cellular innate im ...201526178980
serious adverse events in the canadian registry of children receiving palivizumab (caress) for respiratory syncytial virus prevention.to evaluate the safety and tolerability of palivizumab for rsv prophylaxis in high-risk children in everyday practice.201526237402
epidemiological features of bronchiolitis in the pediatric clinic of clinical center of sarajevo university.to present the epidemiological features of bronchiolitis in a one-year period in patients of pediatric clinic, clinical centre of sarajevo university.201526236159
a metabolomics approach to studying the effects of jinxin oral liquid on rsv-infected mice using uplc/ltq-orbitrap mass spectrometry.jinxin oral liquid (jol) is a traditional chinese medicine (tcm) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. in our previous studies, jol was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (rsv).201526234176
association of respiratory picornaviruses with high acuity and severe illness in a pediatric health care system.we aimed to determine the illness severity associated with respiratory picornaviruses (rhinovirus/enterovirus).201526231633
morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia.the distribution of cilia and the respiratory syncytial virus (rsv) nucleocapsid (n) protein, fusion (f) protein, attachment (g) protein, and m2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). all virus structural proteins were localized at cell surface projections that were distinct from cilia. the f protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the n protein was not detected ...201526231613
building a better neonatal mouse model to understand infant respiratory syncytial virus disease.respiratory syncytial virus (rsv) is the number one cause of lower respiratory tract infection in infants; and severe rsv infection in infants is associated with asthma development. today, there are still no vaccines or specific antiviral therapies against rsv. the mechanisms of rsv pathogenesis in infants remain elusive. this is partly due to the fact that the largely-used mouse model is semi-permissive for rsv. the present study sought to determine if a better neonatal mouse model of rsv infec ...201526231396
hubs to spread technology and save lives.the patent on an expensive preventive treatment for respiratory syncytial virus infections expires this year. a who technology transfer hub in the netherlands aims to help developing countries make the drug themselves. gary humphreys reports.201526229198
viral load in infants hospitalized for respiratory syncytial virus bronchiolitis correlates with recurrent wheezing at thirty-six-month follow-up.the relationship between viral infection, host immune response in infants with respiratory syncytial virus (rsv) bronchiolitis and subsequent wheezing is discussed. we measured rsv-rna load and interferon-λ1-3 expression in the nasopharyngeal washings from 68 infants hospitalized for rsv bronchiolitis, and wheezing was assessed 36 months after the first episode of bronchiolitis. higher rsv-rna load and higher interferon-λ2/3 levels were found in children with recurrent wheezing at 36-month follo ...201526132826
effect of prophylactic palivizumab on admission due to respiratory syncytial virus infection in former very low birth weight infants with bronchopulmonary dysplasia.the aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (rsv) infection (rsvhospitalization) in former very low birth weight infants (vlbwi) with bronchopulmonary dysplasia (bpd). this study also sought to identify the risk factors of rsvhospitalizationin this particular infant population. a prospective observational study was conducted between september 2007 and april 2008 in seven korean hospitals. children with a ...201526130956
a respiratory syncytial virus persistent-infected cell line system reveals the involvement of socs1 in the innate antiviral response.hep-2 cells persistently infected with respiratory syncytial virus (rsv) are a heterogeneous mixture of viral antigen-positive and -negative variants; however, the mechanism through which viral replication becomes latent remains unclear. in this study, we investigated the potential mechanism by which rsv escapes from innate immune surveillance. persistent-infected rsv hep-2 cells were isolated and cell clones were passaged. the rsv-persistent cells produced viruses at a lower titer, resisted wil ...201526122642
clinical endpoints for respiratory syncytial virus prophylaxis trials in infants and children in high-income and middle-income countries.respiratory syncytial virus (rsv) continues to cause significant clinical and economic burden around the world. historically, rsv-associated hospitalization was used as a primary endpoint for rsv prophylaxis trials in infants. however, because of the changing epidemiology and healthcare system landscape, this endpoint has become a critical bottleneck on the pathway to licensure for new therapeutics. a panel of 7 rsv experts was convened (chicago, il, may 22, 2014) to evaluate the challenges of d ...201526121204
detection of multiple respiratory viruses associated with mortality and severity of illness in children.respiratory viral infection is a common source of morbidity and mortality in children. coinfection with multiple viruses occurs frequently; however, the clinical significance of concomitant viral pathogens is unclear. we hypothesized that presence of more than one respiratory virus is associated with increased morbidity and mortality when compared with children with a single respiratory virus.201526121097
antibodies enhance cxcl10 production during rsv infection of infant and adult immune cells.respiratory syncytial virus (rsv) bronchiolitis is a major burden in infants below three months of age, when the primary immune response is mainly dependent on innate immunity and maternal antibodies. we investigated the influence of antibodies on innate immunity during rsv infection. pbmcs from infants and adults were stimulated with live rsv and inactivated rsv in combination with antibody-containing and antibody-depleted serum. the immune response was determined by transcriptome analysis and ...201526253531
alcohol during pregnancy worsens acute respiratory infections in children.this study explored whether alcohol consumption during pregnancy increased the risk of life-threatening respiratory infections in children.201526249835
the changing landscape of respiratory syncytial virus.recognition of the acute and chronic burden of respiratory syncytial virus (rsv) lower respiratory tract infections (lrti) sparked a wave of initiatives to develop preventive and therapeutic products against the pathogen in recent years. rsv is a leading cause of hospitalization in infants in industrialized and developing countries, has been causally linked to recurrent wheezing during childhood, associated with pediatric asthma, and is an important cause of mortality in the first months of life ...201526247900
mammalian cell-derived respiratory syncytial virus-like particles protect the lower as well as the upper respiratory tract.globally, respiratory syncytial virus (rsv) is a leading cause of bronchiolitis and pneumonia in children less than one year of age and in usa alone, between 85,000 and 144,000 infants are hospitalized every year. to date, there is no licensed vaccine. we have evaluated vaccine potential of mammalian cell-derived native rsv virus-like particles (rsv vlps) composed of the two surface glycoproteins g and f, and the matrix protein m. results of in vitro testing showed that the vlps were functionall ...201526172453
influence of respiratory viruses on the evaluation of the 13-valent pneumococcal conjugate vaccine effectiveness in children under 5 years old: a time-series study for the 2001-2013 period.s treptococcus pneumoniae is the main agent in bacterial consolidated pneumonias. in 2012, the 13-valent pneumococcal conjugate vaccine was introduced in the argentine national immunization schedule for immunocompetent children as of two months old with a two-dose schedule plus a booster.201526172005
[research progress in the f gene and protein of the respiratory syncytial virus].the respiratory syncytial virus (rsv) belongs to the family paramyxoviridae and subfamily pneumovirinae. the rsv can cause acute infections of the lower respiratory tract in infants. the f gene of the rsv is a conservative gene and varies only slightly in its expression. few studies focusing on the variability of the f gene have been carried out. f protein (fusion glycoprotein) is a transmembrane glycoprotein that mediates fusion and penetration between the virus and host cells. neutralizing ant ...201526164949
olfactomedin 4 serves as a marker for disease severity in pediatric respiratory syncytial virus (rsv) infection.respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. the transition from mild to severe disease occurs rapidly and is difficult to predict. the pathophysiology underlying disease severity has remained elusive. there is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making.201526162090
sirtuin 1 regulates dendritic cell activation and autophagy during respiratory syncytial virus-induced immune responses.respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infection in children worldwide. sirtuin 1 (sirt1), an nad(+)-dependent deacetylase, has been associated with the induction of autophagy and the regulation of inflammatory mediators. we found that sirt1 was upregulated in mouse lung after rsv infection. infected animals that received ex-527, a selective sirt1 inhibitor, displayed exacerbated lung pathology, with increased mucus production, elevated viral load, and en ...201526157176
respiratory syncytial virus utilizes a trna fragment to suppress antiviral responses through a novel targeting mechanism.target identification is highly instructive in defining the biological roles of micrornas. however, little is known about other small noncoding rnas; for example, trna-derived rna fragments (trfs). some trfs exhibit a gene-silencing mechanism distinctly different from that of typical micrornas. we recently demonstrated that a respiratory syncytial virus (rsv)-induced trf, called trf5-gluctc, promotes rsv replication. rsv is the single most important cause of lower respiratory tract infection in ...201526156244
cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with respiratory syncytial virus.airway epithelial cells (aec) are the first line of defense against airborne infectious microbes and play an important role in regulating the local immune response. however, the interplay of epithelial cells and professional immune cells during both homeostasis and infection has only been partially studied. the present study was performed to determine how bronchial epithelial cells affect the activation of monocytes. under healthy conditions, aecs were shown to inhibit reactivity of monocytes. w ...201526153873
respiratory syncytial virus infections in pediatric transplant recipients: a canadian paediatric surveillance program study.the incidence and spectrum of severity of rsv infections in sot or hsct recipients is not known. from september 2010 through august 2013, pediatricians were surveyed monthly by the cpsp for sot or hsct recipients with rsv infection within two yr post-transplant. there were 24 completed case report forms that fit the inclusion criteria (10 hsct and 14 sot recipients). six of 24 cases (25%) remained outpatients, and 11 (46%) were managed on an inpatient ward, while seven (29%) required intensive c ...201526152857
evaluating vaccination strategies for reducing infant respiratory syncytial virus infection in low-income settings.respiratory syncytial virus (rsv) is a leading cause of lower respiratory tract disease and related hospitalization of young children in least developed countries. individuals are repeatedly infected, but it is the first exposure, often in early infancy, that results in the vast majority of severe rsv disease. unfortunately, due to immunological immaturity, infants are a problematic rsv vaccine target. several trials are ongoing to identify a suitable candidate vaccine and target group, but no i ...201525857701
respiratory syncytial virus fusion protein promotes tlr-4-dependent neutrophil extracellular trap formation by human neutrophils.acute viral bronchiolitis by respiratory syncytial virus (rsv) is the most common respiratory illness in children in the first year of life. rsv bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. neutrophils and their products are present in the airways of rsv-infected patients who developed increased lung disease. neutrophil extracellular traps (nets) are formed by the release of granular and nuclear contents of neutrophils in the extracellular ...201525856628
respiratory syncytial virus, an ongoing medical dilemma: an expert commentary on respiratory syncytial virus prophylactic and therapeutic pharmaceuticals currently in clinical trials.as the most important viral cause of severe respiratory disease in infants and increasing recognition as important in the elderly and immunocompromised, respiratory syncytial virus (rsv) is responsible for a massive health burden worldwide. prophylactic antibodies were successfully developed against rsv. however, their use is restricted to a small group of infants considered at high risk of severe rsv disease. there is still no specific therapeutics or vaccines to combat rsv. as such, it remains ...201525847510
respiratory syncytial virus infection of airway cells: role of micrornas.micrornas (mirnas) are small single-stranded rna molecules involved in the regulation of gene expression at the post-transcriptional level. in the airways, mirnas are implicated in the modulation of antiviral defense, through modulation of both innate and adaptive immune response in inflammatory and immune effector cells but also in parenchymal cells. the first target of respiratory viruses are airway epithelial cells. following infection, an altered expression of distinct mirnas occurs in airwa ...201525847505
[acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].acute tubulointerstitial nephritis (tin) is responsible for nearly 10% of acute renal failure (arf) cases in children. it is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. an immune-competent 13-month-old boy was admitted to the intensive care unit for severe arf with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. the kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, with ...201525842199
correction for kim et al., development of an adenovirus-based respiratory syncytial virus vaccine: preclinical evaluation of efficacy, immunogenicity, and enhanced disease in a cotton rat model. 201525841050
effect of young sibling visitation on respiratory syncytial virus activity in a nicu.to determine whether the restriction of young sibling (<13 years) visitation in the neonatal intensive care unit (nicu) during the respiratory syncytial virus (rsv) season was associated with a reduction in the rate of rsv infection among nicu patients.201525836315
respiratory syncytial virus infection of primary human mast cells induces the selective production of type i interferons, cxcl10, and ccl4.respiratory syncytial virus (rsv) causes severe respiratory tract infections, which might have a role in the development of airway hyperreactivity. mast cells are important effector cells in allergy, with sentinel cell roles in host defense. however, the role of mast cells in response to rsv infection is unknown.201525819983
neutralizing epitopes on the respiratory syncytial virus fusion glycoprotein.respiratory syncytial virus (rsv) is a leading cause of pneumonia and bronchiolitis, but despite decades of research a safe and effective vaccine has remained elusive. the viral fusion glycoprotein (rsv f) plays an obligatory role in the entry process and is the major target of neutralizing antibodies, making it an attractive target for vaccine development. this review will summarize the recently determined structures of rsv f in the prefusion and postfusion conformations and describe the locati ...201525819327
[approach to a respiratory syncytial virus outbreak related to medical care in hematology]. 201525817393
self-sampling for analysis of respiratory viruses in a large-scale epidemiological study in sweden.viral diagnosis of respiratory tract infections has so far required sampling by health professionals,hampering large-scale epidemiological studies of virus-specific disease outcomes. as part of a population-based, prospective study of work-related risk factors for transmission of viral infections (swede-i), we developed a scheme for self-sampling with nasal swabs. random selection from the gainfully employed population of a medium-sized town in central sweden resulted in a study cohort of 2,237 ...201525811646
bd veritor system respiratory syncytial virus rapid antigen detection test: point-of-care results in primary care pediatric offices compared with reverse transcriptase polymerase chain reaction and viral culture methods.during respiratory syncytial virus season, many children present to pediatric offices and urgent care medical facilities with cough, tachypnea, intercostal retraction, wheezing, as well as disturbed appetite and sleep. identification of the responsible viral pathogen is quite difficult because several pathogens can produce similar signs and symptoms.201525803752
superinfection between influenza and rsv alternating patterns in san luis potosí state, méxico.the objective of this paper is to explain through the ecological hypothesis superinfection and competitive interaction between two viral populations and niche (host) availability, the alternating patterns of respiratory syncytial virus (rsv) and influenza observed in a regional hospital in san luis potosí state, méxico using a mathematical model as a methodological tool. the data analyzed consists of community-based and hospital-based acute respiratory infections (ari) consultations provided by ...201525803450
association between respiratory viruses and exacerbation of copd: a case-control study.respiratory viral infection is the main cause of exacerbations of chronic obstructive pulmonary disease (copd) in all age groups. the present study aimed to find out the association between viral infection in exacerbated and stable patients with copd as well as evaluating the frequency of respiratory viruses in the iranian exacerbated patients.201525800059
decapping protein 1 phosphorylation modulates il-8 expression during respiratory syncytial virus infection.respiratory syncytial virus (rsv) is a negative-strand rna virus that is an important cause of bronchiolitis and pneumonia. we investigated the effect of rsv infection on the expression patterns of cellular proteins involved in regulating mrna translation and degradation, and found that a processing-body protein involved in mrna degradation, decapping protein 1a (dcp1), was phosphorylated rapidly following infection. uv-inactivated and sucrose-purified rsv were sufficient to mediate dcp1 phospho ...201525796077
titanium dioxide nanoparticles exacerbate pneumonia in respiratory syncytial virus (rsv)-infected mice.to reveal the effects of tio2 nanoparticles, used in cosmetics and building materials, on the immune response, a respiratory syncytial virus (rsv) infection mouse model was used. balb/c mice were exposed once intranasally to tio2 at 0.5mg/kg and infected intranasally with rsv five days later. the levels of ifn-γ and chemokine ccl5, representative markers of pneumonia, in the bronchoalveolar lavage fluids of rsv-infected mice had increased significantly in tio2-exposed mice compared with the cont ...201525795424
a novel respiratory syncytial virus (rsv) f subunit vaccine adjuvanted with gla-se elicits robust protective th1-type humoral and cellular immunity in rodent models.illness associated with respiratory syncytial virus (rsv) remains an unmet medical need in both full-term infants and older adults. the fusion glycoprotein (f) of rsv, which plays a key role in rsv infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing rsv-specific immunity.201525793508
value of a risk scoring tool to predict respiratory syncytial virus disease severity and need for hospitalization in term infants.several environmental and demographic risk factors have been validated and are used to determine the risk of acquiring severe respiratory syncytial virus (rsv) infection and subsequent hospitalization in late preterm infants born at 33-35 weeks gestational age. the applicability of the same composite model of risk factors in the term population has not been fully explored. the primary objective of this pilot study was to establish whether a risk scoring tool (rst), could predict the severity of ...201525784593
continuous positive airway pressure with helmet versus mask in infants with bronchiolitis: an rct.noninvasive continuous positive airway pressure (cpap) is usually applied with a nasal or facial mask to treat mild acute respiratory failure (arf) in infants. a pediatric helmet has now been introduced in clinical practice to deliver cpap. this study compared treatment failure rates during cpap delivered by helmet or facial mask in infants with respiratory syncytial virus-induced arf.201525780074
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