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population pharmacokinetic modeling of jnj-53718678, a novel fusion inhibitor for the treatment of respiratory syncytial virus: results from a phase i, double-blind, randomized, placebo-controlled first-in-human study in healthy adult subjects.jnj-53718678 is a potent small-molecule inhibitor of the f-glycoprotein-mediated complex membrane fusion process of the respiratory syncytial virus. here, we report the pharmacokinetics, the population pharmacokinetic modeling, and the safety and tolerability of jnj-53718678 from the first-in-human, double-blind, randomized, placebo-controlled phase i study.201728238203
impact of the 2014 american academy of pediatrics guidance on respiratory syncytial virus and bronchiolitis hospitalization rates for infants born prematurely. 201728237377
one-year observational study of palivizumab prophylaxis on infants at risk for respiratory syncytial virus infection in latin america.this study aims to describe real world palivizumab use and effectiveness in high-risk latin american infants and young children.201728236418
sensitive detection of respiratory syncytial virus based on a dual signal amplified plasmonic enzyme-linked immunosorbent assay.the timely detection of infectious pathogen is critical in clinical early diagnosis and treatment of infectious diseases. plasmonic enzyme-linked immunosorbent assay (elisa), by means of enzyme-mediated growth or aggregation of aunps, has received considerable attention because it allows a naked-eye detection of target in very low numbers. in this work, a dual-signal amplified plasmonic elisa combined the high loading capacity of magnetic beads with the establishing stimulation effect of zinc io ...201728231882
respiratory syncytial virus infects regulatory b cells in human neonates via chemokine receptor cx3cr1 and promotes lung disease severity.respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of b cells in fatal cases. we analyzed the b cell compartment in human newborns and identified a population of neonatal regulatory b lymphocytes (nbreg cells) that produced interleukin 10 (il-10) in response to rsv infection. the polyreactive b cell receptor of nbreg cells interacted with rsv protein f and induced upregulation of chemokine receptor ...201728228284
protective and harmful immunity to rsv infection.respiratory syncytial virus (rsv) is an exceptional mucosal pathogen. it specializes in infection of the ciliated respiratory epithelium, causing disease of variable severity with little or no direct systemic effects. it infects virtually all children by the age of three years and then repeatedly infects throughout life; this it does despite relatively slight variations in antigenicity, apparently by inducing selective immunological amnesia. inappropriate or dysregulated responses to rsv can be ...201728226227
feasibility of multiple breath washout measurements in infants with bronchiolitis: a pilot study.lung clearance index (lci) reflects ventilation inhomogeneity and is raised in obstructive airway disease. feasibility of multiple breath washout (mbw) measurement during acute lung disease in infants is unknown. as a further measure of disease, exhaled nitric oxide (eno) may paradoxically decrease in acute bronchiolitis. we hypothesized that mbw measurements were attainable in infants with bronchiolitis and that lci was raised and eno reduced, compared to normal controls.201728221737
comparing first- and second-year palivizumab prophylaxis in patients with hemodynamically significant congenital heart disease in the caress database (2005-2015).respiratory syncytial virus hospitalization (rsvh) rates in children <2 years of age with hemodynamically significant congenital heart disease (hschd) are 2- to 4-fold higher compared with healthy term infants. pediatric recommendations differ as to whether palivizumab is beneficial beyond 1 year of age. the objective of this study was to determine whether differences exist in respiratory-related illness hospitalization (rih) and rsvh in hschd infants receiving palivizumab during the first year ...201728403044
maternal immunization.pregnant women, neonates, and infants are at higher risk for severe infections due to vaccine-preventable diseases. very young infants rarely respond well to vaccination due to poor immunogenicity and interference from maternal antibody. maternal immunization protects the mother and fetus from disease and protects the infant through transplacental antibody transfer through the first 6 months of life. currently, immunizations routinely recommended during pregnancy include inactivated influenza, t ...201728398678
a clinical companion to the nice guide on bronchiolitis.the national institute for health and care excellence (nice) ( 2015 ) defines bronchiolitis as a lower respiratory tract infection affecting children under two years, peaking between three and six months. it affects about one in three infants in the first year of life, making it the most common respiratory infection in infants ( nice 2015 , 2016 ). of these infants, 2-3% will require admission to hospital ( nice 2016 ). respiratory syncytial virus (rsv) is the most common organism detected in th ...201728395629
aptamers for respiratory syncytial virus detection.the identification of the infectious agents is pivotal for appropriate care of patients with viral diseases. current viral diagnostics rely on selective detection of viral nucleic acid or protein components. in general, detection of proteins rather than nucleic acids is technically more suitable for rapid tests. however, protein-based virus identification methods depend on antibodies limiting the practical applicability of these approaches. aptamers rival antibodies in target selectivity and bin ...201728220811
natural helper cells are associated with the exacerbated airway inflammation seen during rsv reinfection of neonatally primed mice.infection with respiratory syncytial virus (rsv) in neonatal mice causes more aggressive airway disease when the mice are reinfected with the same virus as adults. however, the underlying mechanisms responsible for this phenomenon are not entirely defined. natural helper (nh) cells are considered a key factor for virus-induced or exacerbated airway inflammation and airway hyper-responsiveness by producing type 2 cytokines. to confirm whether nh cells are involved in the aggravated lung pathology ...201728219838
neutralization of nerve growth factor (ngf) inhibits the th2 response and protects against the respiratory syncytial virus (rsv) infection.increasing evidence suggests that respiratory syncytial virus (rsv) infection during the early life is an important risk factor for the development of asthma. rsv infection is associated with neurogenic inflammation in the airways along with the increased expression of nerve growth factor (ngf). however, the role of ngf in rsv infection is not clear. in this study, we infected the rat with rsv and treated these animals with anti-ngf neutralization antibody. we found that anti-ngf treatment signi ...201728258348
systematic analysis of cell-type differences in the epithelial secretome reveals insights into the pathogenesis of respiratory syncytial virus-induced lower respiratory tract infections.lower respiratory tract infections from respiratory syncytial virus (rsv) are due, in part, to secreted signals from lower airway cells that modify the immune response and trigger airway remodeling. to understand this process, we applied an unbiased quantitative proteomics analysis of the rsv-induced epithelial secretory response in cells representative of the trachea versus small airway bronchiolar cells. a workflow was established using telomerase-immortalized human epithelial cells that revea ...201728258195
indications to respiratory syncytial virus immunoprophylaxis in the 29-32 wga group: is there still room for debating?guidelines on immunoprophylaxis for prevention of rsv infection recommend it in preterm babies born before 29 wga; in babies affected by bronchopulmonary dysplasia or congenital heart defects; and in post-heart transplantation patients. on the contrary, immunoprophylaxis is not recommended in preterm babies born between 29 and 35 wga. we evaluated the impact of rsv-related healthcare expenditures in infants in the first 3 years of life in italy, lombardy region. in light of the collected data an ...201728257653
crucial roles of reactive chemical species in modification of respiratory syncytial virus by nitrogen gas plasma.the exact mechanisms by which nanoparticles, especially those composed of soft materials, are modified by gas plasma remain unclear. here, we used respiratory syncytial virus (rsv), which has a diameter of 80-350nm, as a model system to identify important factors for gas plasma modification of nanoparticles composed of soft materials. nitrogen gas plasma, generated by applying a short high-voltage pulse using a static induction (si) thyristor power supply produced reactive chemical species (rcs) ...201728254277
reduced prf1 enhancer methylation in children with a history of severe rsv bronchiolitis in infancy: an association study.acute lower respiratory tract infection is the commonest disease affecting children under five worldwide. respiratory syncytial virus (rsv) is among the most common causative pathogens. epidemiological data suggest an association between severe viral respiratory infections in infancy and increased incidence of childhood wheeze and asthma. dna methylation is involved in immune cell differentiation and identity. it provides an avenue for environmental influences on the genome and therefore has pot ...201728253869
respiratory syncytial virus hospitalization risk in the second year of life by specific congenital heart disease diagnoses.children with hemodynamically significant congenital heart disease (chd) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (rsv) disease compared to their healthy peers. previous studies have demonstrated lower rsv hospitalization risk among all children with chd at 12-23 months of age versus 0-11 months of age. however, rsv hospitalization risk at 12-23 months of age by specific chd diagnosis has not been characterized. both case-control and cohort studies were ...201728253361
identification of non-nucleoside inhibitors of the respiratory syncytial virus polymerase complex.respiratory syncytial virus (rsv) represents a threat to infants, the elderly, and the immunocompromised. rsv entry blockers are in clinical trials, but escape mutations challenge their potential. in search of rsv inhibitors, we have integrated a signature resistance mutation into a recombinant rsv virus and applied the strain to high-throughput screening. counterscreening of candidates returned 14 confirmed hits with activities in the nano- to low-micromolar range. all blocked rsv polymerase ac ...201728245119
modulation of the host immune response by respiratory syncytial virus proteins.respiratory syncytial virus (rsv) causes severe respiratory disease in both the very young and the elderly. nearly all individuals become infected in early childhood, and reinfections with the virus are common throughout life. despite its clinical impact, there remains no licensed rsv vaccine. rsv infection in the respiratory tract induces an inflammatory response by the host to facilitate efficient clearance of the virus. however, the host immune response also contributes to the respiratory dis ...201728243940
the clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit.although many reports have already shown rsv outbreaks among hemato-oncology patients, genomic studies detecting similar rsv strains prior to an outbreak in the hospital are rare. in 2014, the university of the ryukyus hospital hemato-oncology unit experienced, and successfully managed, a respiratory syncytial virus (rsv) nosocomial outbreak. during the outbreak investigation, genotyping and phylogenetic analysis was used to identify a potential source for the outbreak. nasopharyngeal swabs were ...201728240370
post-extubation stridor in respiratory syncytial virus bronchiolitis: is there a role for prophylactic dexamethasone?the purpose of this study was to determine the incidence of reintubation due to upper airway obstruction in a homogeneous group of ventilated infants with respiratory syncytial virus bronchiolitis. our secondary objective was to determine whether prophylactic administration of dexamethasone prior to extubation was associated with decreased risk of reintubation.201728207796
respiratory syncytial virus (rsv) infects cd4+ t cells: frequency of circulating cd4+ rsv+ t cells as a marker of disease severity in young children.although human airway epithelial cells are the main target of respiratory syncytial virus (rsv), it also infects immune cells, such as macrophages and b cells. whether t cells are permissive to rsv infection is unknown. we sought to analyze the permissiveness of cd4+ t cells to rsv infection.201728199704
cpg in combination with an inhibitor of notch signaling suppresses formalin-inactivated respiratory syncytial virus-enhanced airway hyperresponsiveness and inflammation by inhibiting th17 memory responses and promoting tissue-resident memory cells in lungs.respiratory syncytial virus (rsv) is the leading cause of childhood hospitalizations. the formalin-inactivated rsv (fi-rsv) vaccine-enhanced respiratory disease (erd) has been an obstacle to the development of a safe and effective killed rsv vaccine. agonists of toll-like receptor (tlr) have been shown to regulate immune responses induced by fi-rsv. notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. cross talk bet ...201728275186
the interdependencies of viral load, the innate immune response, and clinical outcome in children presenting to the emergency department with respiratory syncytial virus-associated bronchiolitis.respiratory syncytial virus (rsv) causes significant infant morbidity and mortality. for decades severe rsv-induced disease was thought to result from an uncontrolled host response to viral replication, but recent work suggests that a strong innate immune response early in infection is protective. to shed light on host-virus interactions and the viral determinants of disease, copy numbers of five rsv genes (ns1, ns2, n, g, f) were measured by quantitative real-time polymerase chain reaction (qpc ...201728267794
the influence of the microbiome on early-life severe viral lower respiratory infections and asthma-food for thought?severe viral lower respiratory infections are a major cause of infant morbidity. in developing countries, respiratory syncytial virus (rsv)-bronchiolitis induces significant mortality, whereas in developed nations the disease represents a major risk factor for subsequent asthma. susceptibility to severe rsv-bronchiolitis is governed by gene-environmental interactions that affect the host response to rsv infection. emerging evidence suggests that the excessive inflammatory response and ensuing im ...201728261214
pitfalls in interpretation of ct-values of rt-pcr in children with acute respiratory tract infections.the relation between viral load and disease severity in childhood acute respiratory tract infections (ari) is not fully understood.201728259567
in reply: completed weeks of gestation and risk of respiratory syncytial virus in late preterm infants. 201728198790
viral aetiology of bronchiolitis in hospitalised children in qatar.bronchiolitis is considered one of the earliest and most common causes of hospitalisation in young children. development of molecular technologies allowed a better understanding of bronchiolitis aetiology. results from cohort studies evaluating the association between single, multiple viral infections and clinical outcomes are conflicting. data on viral bronchiolitis in children were found to be limited in qatar. this study aimed to determine frequency and seasonal trends of viral pathogens caus ...201728193180
palivizumab exposure and the risk of atopic dermatitis, asthma and allergic rhinoconjunctivitis: a cross-national, population-based cohort study.palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus. it is prescribed to children at high risk for severe infection with respiratory syncytial virus. however, little is known about the risk of the immune-mediated diseases atopic dermatitis, asthma, and allergic rhinoconjunctivitis after palivizumab exposure.201728188494
in reply: statistical power to detect an association between guideline-based palivizumab administration and hospitalizations for respiratory syncytial virus infections. 201728187117
statistical power to detect an association between guideline-based palivizumab administration and hospitalizations for respiratory syncytial virus infections. 201728187116
immunization with low doses of recombinant postfusion or prefusion respiratory syncytial virus f primes for vaccine-enhanced disease in the cotton rat model independently of the presence of a th1-biasing (gla-se) or th2-biasing (alum) adjuvant.respiratory syncytial virus (rsv) infection of children previously immunized with a nonlive, formalin-inactivated (fi)-rsv vaccine has been associated with serious enhanced respiratory disease (erd). consequently, detailed studies of potential erd are a critical step in the development of nonlive rsv vaccines targeting rsv-naive children and infants. the fusion glycoprotein (f) of rsv in either its postfusion (post-f) or prefusion (pre-f) conformation is a target for neutralizing antibodies and ...201728148790
in vitro screening for antiviral activity of turkish plants revealing methanolic extract of rindera lanata var. lanata active against human rotavirus.human rotavirus (hrov) is the leading cause of severe gastroenteritis in infants and children under the age of five years. no specific antiviral drug is available for hrov infections and the treatment of viral diarrhea is mainly based on rehydration and zinc treatment. in this study, we explored medicinal plants endemic to turkey flora as a source of anti-hrov compunds.201728118832
a short double-stapled peptide inhibits respiratory syncytial virus entry and spreading.synthetic peptides derived from the heptad repeat (hr) of fusion (f) proteins can be used as dominant negative inhibitors to inhibit the fusion mechanism of class i viral f proteins. here, we have performed a stapled-peptide scan across the hr2 domain of the respiratory syncytial virus (rsv) f protein with the aim to identify a minimal domain capable of disrupting the formation of the postfusion six-helix bundle required for viral cell entry. constraining the peptides with a single staple was no ...201728137809
characteristics of rsv-specific maternal antibodies in plasma of hospitalized, acute rsv patients under three months of age.respiratory syncytial virus (rsv) is the leading cause for respiratory illness that requires hospitalization in infancy. high levels of maternal antibodies can protect against rsv infection. however, rsv-infected infants can suffer from severe disease symptoms even in the presence of high levels of rsv-specific antibodies. this study analyzes several serological characteristics to explore potential deficiencies or surpluses of antibodies that could relate to severe disease symptoms. we compare s ...201728135305
a novel pre-fusion conformation-specific neutralizing epitope on the respiratory syncytial virus fusion protein.respiratory syncytial virus (rsv) remains a major human pathogen, infecting the majority of infants before age two and causing re-infection throughout life. despite decades of rsv research, there is no licensed rsv vaccine. most candidate vaccines studied to date have incorporated the rsv fusion (f) surface glycoprotein, because the sequence of f is highly conserved among strains of rsv. to better define the human b cell response to rsv f, we isolated from a single donor 13 new neutralizing huma ...201728134924
the diagnosis and management of respiratory viral infections in cystic fibrosis.respiratory viruses, such as those that cause influenza and the common cold, are a regular feature of life for the entire human population. among people with cf, these viruses are associated with prolonged respiratory illness and show a clear association with pulmonary exacerbations which in turn are associated with lung function decline and risk of death. human rhinovirus is the most commonly encountered respiratory viral pathogen in cf although adenovirus, bocavirus, coronavirus, influenza, pa ...201728132571
virus-like particle vaccines containing f or f and g proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats.vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (rsv). this study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (vlp) vaccines containing rsv f (f vlp), g (g vlp), or f and g proteins (fg vlp) in cotton rats. rsv specific antibodies were effectively induced by vaccination of cotton rats with f vlp or fg vlp vaccines. after challenge, lung rsv clearance was observed with rsv f, g, fg vlp, and formal ...201728129031
educating parents about the vaccination status of their children: a user-centered mobile application.parents are often uncertain about the vaccination status of their children. in times of vaccine hesitancy, vaccination programs could benefit from active patient participation. the vaccination app (vaccapp) was developed by the vienna vaccine safety initiative, enabling parents to learn about the vaccination status of their children, including 25 different routine, special indication and travel vaccines listed in the who immunization certificate of vaccination (who-icv). between 2012 and 2014, t ...201728127527
high flow nasal cannula (hfnc) versus nasal continuous positive airway pressure (ncpap) for the initial respiratory management of acute viral bronchiolitis in young infants: a multicenter randomized controlled trial (tramontane study).nasal continuous positive airway pressure (ncpap) is currently the gold standard for respiratory support for moderate to severe acute viral bronchiolitis (avb). although oxygen delivery via high flow nasal cannula (hfnc) is increasingly used, evidence of its efficacy and safety is lacking in infants.201728124736
correlation of symptomatic enterovirus infection and later risk of allergic diseases via a population-based cohort study.infants who are exposed to the rhinovirus or respiratory syncytial virus are at a higher risk of subsequently developing wheezing or asthma. this study aims to determine whether preschoolers with a history of symptomatic enterovirus infection are at an increased risk of developing allergic diseases or not.we used data from the taiwan national health insurance research database from 1999 to 2006 for this nationwide population-based cohort study. the subsequent risks for allergic diseases, which i ...201728121929
lower respiratory tract diseases caused by common respiratory viruses among stem cell transplantation recipients: a single center experience in korea.to describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (lrds) caused by common respiratory viruses (crvs) in stem cell transplantation (sct) recipients.201728120567
use of an automated nested multiplex respiratory pathogen pcr panel postmortem in the pediatric forensic setting.respiratory pathogens have been detected in forensic investigations using multiple techniques; however, no study has examined the use of automated, nested, multiplex polymerase chain reaction (anm-pcr), commonly used in living patients, in the forensic setting. this retrospective study assessed the utility of anm-pcr in detecting respiratory pathogens in the pediatric forensic setting. respiratory samples from 35 cases were tested for up to 20 respiratory pathogens. 51.4% of these cases yielded ...201728120330
human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality.human rhinoviruses are the most common respiratory viruses detected in patients after hematopoietic cell transplantation. although rhinovirus appears to occasionally cause severe lower respiratory tract infection in immunocompromised patients, the clinical significance of rhinovirus detection in the lower respiratory tract remains unknown. we evaluated 697 recipients transplanted between 1993 and 2015 with rhinovirus in respiratory samples. as comparative cohorts, 273 recipients with lower respi ...201728183847
rapid and sensitive real-time assay for the detection of respiratory syncytial virus using rt-siba®.respiratory syncytial virus (rsv) is one of the most common causes of respiratory tract infections among young children and the elderly. timely and accurate diagnosis of respiratory tract infections improves patient care and minimizes unnecessary prescriptions of antibiotics. we sought to develop a rapid nucleic acid tests for the detection of rsv within minutes, while retaining the high sensitivity achieved with rt-pcr.201728183291
the human immune response to respiratory syncytial virus infection.respiratory syncytial virus (rsv) is an important etiological agent of respiratory infections, particularly in children. much information regarding the immune response to rsv comes from animal models and in vitro studies. here, we provide a comprehensive description of the human immune response to rsv infection, based on a systematic literature review of research on infected humans. there is an initial strong neutrophil response to rsv infection in humans, which is positively correlated with dis ...201728179378
prenatal exposure to respiratory syncytial virus alters postnatal immunity and airway smooth muscle contractility during early-life reinfections.maternal viral infections can have pathological effects on the developing fetus which last long after birth. recently, maternal-fetal transmission of respiratory syncytial virus (rsv) was shown to cause postnatal airway hyperreactivity (ahr) during primary early-life reinfection; however, the influence of prenatal exposure to rsv on offspring airway immunity and smooth muscle contractility during recurrent postnatal reinfections remains unknown. therefore, we sought to determine whether maternal ...201728178290
[clinical value of a rapid respiratory syncytial virus antigen detection in point-of-care testing].objective: to evaluate the clinical value of a rapid respiratory syncytial virus (rsv) antigen detection in point-of-care testing (poct). method: a total of 209 specimens, including 78 throat swabs (ts) and 131 nasopharyngeal aspirates (npas), were collected from inpatients who visited the children's hospital affiliated to the capital institute of pediatrics and were diagnosed as acute respiratory infection from 5 january to 7 february, 2015. these specimens were tested for rsv by a rapid antige ...201728173654
a narrowing diagnosis: a rare cause of adult croup and literature review.croup or laryngotracheitis is rare in adults. we present a case of an otherwise healthy young woman that presented in the winter with 3 days of increasing dyspnea, cough, and fever. she was hemodynamically stable but was found to have a barking cough, paradoxical abdominal breathing, and stridor. chest radiograph revealed subglottic narrowing. respiratory viral nucleic acid amplification testing was positive for respiratory syncytial virus. the patient was treated with nebulized epinephrine, dex ...201728163937
respiratory syncytial virus hospitalizations in infants of 28 weeks gestational age and less in the palivizumab era.to obtain data on respiratory syncytial virus (rsv) associated hospitalization rates in preterm infants of 28 weeks gestational age and less in the era of palivizumab prophylaxis.201728163166
immune and inflammatory response in bronchiolitis due to respiratory syncytial virus and rhinovirus infections in infants.bronchiolitis is a common disease in infancy, mostly due to respiratory syncytial virus and rhinovirus. in addition to acute infection, viral bronchiolitis is responsible for sequelae including recurrent wheezing and asthma. the analysis of the viral characteristics and of the pathogenesis of the infection shows differences between the two viruses that may be helpful for the development of therapies and preventive strategies.201728159510
respiratory syncytial virus infection: an illness for all ages.respiratory syncytial virus (rsv) is the single most important cause of severe respiratory infection in very young infants. it has also been recently recognized as a significant cause of severe illness in elderly adults, those with underlying cardiopulmonary disease, and the immunocompromised. rsv is suspected of playing a major role in the development of asthma. prophylaxis in high-risk infants using a monoclonal antibody is the only effective specific therapy available but recent breakthroughs ...201728159159
vaccines in the prevention of viral pneumonia.pneumonia is of great global public health importance. viral infections play both direct and indirect parts in its cause across the globe. influenza is a leading cause of viral pneumonia in both children and adults, and respiratory syncytial virus is increasingly recognized as causing disease at both extremes of age. vaccination offers the best prospect for prevention but current influenza vaccines do not provide universal and durable protection, and require yearly reformulation. in the future, ...201728159157
respiratory syncytial virus infection induces a subset of types i and iii interferons in human dendritic cells.whether respiratory syncytial virus (rsv) induces severe infantile pulmonary disease may depend on viral strain and expression of types i and iii interferons (ifns). these ifns impact disease severity by inducing expression of many anti-viral ifn-stimulated genes (isgs). to investigate the impact of rsv strain on ifn and isg expression, we stimulated human monocyte-derived dcs (mddcs) with either rsv a2 or line 19 and measured expression of types i and iii ifns and isgs. at 24h, a2 elicited high ...201728157546
caveolae provide a specialized membrane environment for respiratory syncytial virus assembly.respiratory syncytial virus (rsv) is an enveloped virus that assembles into filamentous virus particles on the surface of infected cells. morphogenesis of rsv is dependent upon cholesterol-rich (lipid raft) membrane microdomains, but the specific role of individual raft molecules in rsv assembly is not well defined. here, we show that rsv morphogenesis occurs within caveolar membranes and that both caveolin-1 and cavin-1 (also known as ptrf), the two major structural and functional components of ...201728154158
palivizumab prophylaxis in preterm infants and subsequent recurrent wheezing. six-year follow-up study.respiratory syncytial virus (rsv) induces not only infantile recurrent wheezing but also potentially atopic asthma.201728152315
respiratory syncytial virus, infants and intensive therapy.the aims of this study were to determine the presence of respiratory syncytial virus (rsv) and to assess the clinical features of the disease in infants with acute low respiratory tract infection hospitalized at pediatric intensive care units (picu) of two university teaching hospitals in são paulo state, brazil. nasopharyngeal secretions were tested for the rsv by the polymerase chain reaction. positive and negative groups for the virus were compared in terms of evolution under intensive care ( ...201722358363
cholesterol is required for stability and infectivity of influenza a and respiratory syncytial viruses.cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. however, the functional role of cholesterol in assembly, infectivity and stability of respiratory rna viruses is not fully understood. we previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hpiv1) particles by inhibiting virus assembly. in this study, we analyzed the ro ...201728750327
mammalian diaphanous-related formin-1 restricts early phases of influenza a/nws/33 virus (h1n1) infection in llc-mk2 cells by affecting cytoskeleton dynamics.viruses depend on cellular machinery to efficiently replicate. the host cytoskeleton is one of the first cellular systems hijacked by viruses in order to ensure their intracellular transport and promote the development of infection. our previous results demonstrated that stable microfilaments and microtubules interfered with human influenza a/nws/33 virus (h1n1) infection in semi-permissive llc-mk2 cells. although formins play a key role in cytoskeletal remodelling, few studies addressed a possi ...201728744815
mirna-200c-3p is crucial in acute respiratory distress syndrome.influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ards), which is the most severe form of acute lung injury (ali). angiotensin-converting enzyme 2 (ace2), which is a negative regulator of angiotensin ii in the renin-angiotensin system, has been reported to have a crucial role in ali. downregulation of ace2 is always associated with the ali or ards induced by avian influenza virus, severe acute respiratory syndrome-corona ...201728690868
inhibition of highly pathogenic avian influenza (hpai) virus by a peptide derived from vflip through its direct destabilization of viruses.the antiviral activities of synthesized kα2-helix peptide, which was derived from the viral flice-like inhibitor protein (vflip) of kaposi's sarcoma-associated herpesvirus (kshv), against influenza a virus (iav) were investigated in vitro and in vivo, and mechanisms of action were suggested. in addition to the robust autophagy activity of the kα2-helix peptide, the present study showed that treatment with the kα2 peptide fused with the tat peptide significantly inhibited iav replication and tran ...201728687749
broad-spectrum inhibition of common respiratory rna viruses by a pyrimidine synthesis inhibitor with involvement of the host antiviral response.our previous screening of 50 240 structurally diverse compounds led to the identification of 39 influenza a virus infection inhibitors (kao r.y., yang d., lau l.s., tsui w.h., hu l. et al. nat biotechnol 2010;28:600-605). further screening of these compounds against common respiratory viruses led to the discovery of compound fa-613. this inhibitor exhibited low micromolar antiviral activity against various influenza a and b virus strains, including the highly pathogenic influenza a strains h5n1 ...201728555543
multicenter clinical evaluation of the luminex aries flu a/b & rsv assay for pediatric and adult respiratory tract specimens.influenza a and b viruses and respiratory syncytial virus (rsv) are three common viruses implicated in seasonal respiratory tract infections and are a major cause of morbidity and mortality in adults and children worldwide. in recent years, an increasing number of commercial molecular tests have become available to diagnose respiratory viral infections. the luminex aries flu a/b & rsv assay is a fully automated sample-to-answer molecular diagnostic assay for the detection of influenza a, influen ...201728539342
respiratory viral infections are underdiagnosed in patients with suspected sepsis.the study aim was to investigate the prevalence and clinical relevance of viral findings by multiplex pcr from the nasopharynx of clinically septic patients during a winter season. during 11 weeks of the influenza epidemic period in january-march 2012, consecutive adult patients suspected to be septic (n = 432) were analyzed with cultures from blood and nasopharynx plus multiplex pcr for respiratory viruses on the nasopharyngeal specimen. the results were compared with those from microbiology an ...201728516200
inflammatory responses regulating alveolar ion transport during pulmonary infections.the respiratory epithelium is lined by a tightly balanced fluid layer that allows normal o2 and co2 exchange and maintains surface tension and host defense. to maintain alveolar fluid homeostasis, both the integrity of the alveolar-capillary barrier and the expression of epithelial ion channels and pumps are necessary to establish a vectorial ion gradient. however, during pulmonary infection, auto- and/or paracrine-acting mediators induce pathophysiological changes of the alveolar-capillary barr ...201728458673
a metagenomics study for the identification of respiratory viruses in mixed clinical specimens: an application of the iterative mapping approach.metagenomic approaches to detect viral genomes and variants in clinical samples have various challenges, including low viral titers and bacterial and human genome contamination. to address these limitations, we examined a next-generation sequencing (ngs) and iterative mapping approach for virus detection in clinical samples. we analyzed 40 clinical specimens from hospitalized children diagnosed with acute bronchiolitis, croup, or respiratory tract infections in which virus identification by vira ...201728424887
antiviral activity of chlorogenic acid against influenza a (h1n1/h3n2) virus and its inhibition of neuraminidase.lonicera japonica thunb, rich in chlorogenic acid (cha), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in china. it was reported that cha reduced serum hepatitis b virus level and death rate of influenza virus-infected mice. however, the underlying mechanisms of cha against the influenza a virus have not been fully elucidated. here, the antiviral effects and potential mechanisms of cha against in ...201728393840
macromolecular prodrugs of ribavirin: structure-function correlation as inhibitors of influenza infectivity.the requirement for new antiviral therapeutics is an ever present need. particularly lacking are broad spectrum antivirals that have low toxicity. we develop such agents based on macromolecular prodrugs whereby both the polymer chain and the drug released from the polymer upon cell entry have antiviral effects. specifically, macromolecular prodrugs were designed herein based on poly(methacrylic acid) and ribavirin. structure-function parameter space was analyzed via the synthesis of 10 polymer c ...201728043136
the genetic stability of piv5-vectored rsv vaccine candidates after in vitro and in vivo passage.human respiratory syncytial virus (rsv) is the leading etiologic agent of lower respiratory tract infections in children, but no licensed vaccine exists. previously, our laboratory developed two parainfluenza virus 5 (piv5)-based rsv vaccine candidates that protect mice against rsv challenge. piv5 was engineered to express either the rsv fusion protein (f) or the rsv major attachment glycoprotein (g) between the hn and l genes of the piv5 genome [piv5-rsv-f (hn-l) or piv5-rsv-g (hn-l)]. to inves ...201728747497
respiratory virus infection up-regulates trpv1, trpa1 and asics3 receptors on airway cells.receptors implicated in cough hypersensitivity are transient receptor potential vanilloid 1 (trpv1), transient receptor potential cation channel, subfamily a, member 1 (trpa1) and acid sensing ion channel receptor 3 (asic3). respiratory viruses, such as respiratory syncytial virus (rsv) and measles virus (mv) may interact directly and/or indirectly with these receptors on sensory nerves and epithelial cells in the airways. we used in vitro models of sensory neurones (shsy5y or differentiated imr ...201728187208
etiology and clinical features of viral bronchiolitis in infancy.bronchiolitis is a common lower respiratory tract infection in infancy. the aim of this review is to present the clinical profile of viral bronchiolitis, the different culprit viruses and the disease severity in relation to the viral etiology.201728470580
risk of respiratory syncytial virus hospitalization in the first and second years of life in pediatric patients with congenital heart disease. 201728536747
discovery of a prefusion respiratory syncytial virus f-specific monoclonal antibody that provides greater in vivo protection than the murine precursor of palivizumab.palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site ii on both the prefusion (pre-f) and postfusion (post-f) conformations of the respiratory syncytial virus (rsv) f glycoprotein, is the only prophylactic agent approved for use for the treatment of rsv infection. however, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. previously, we isolated a high-potency neutralizing ...201728539438
airway t cells protect against rsv infection in the absence of antibody.tissue resident memory t (trm) cells act as sentinels and early responders to infection. respiratory syncytial virus (rsv)-specific trm cells have been detected in the lungs after human rsv infection, but whether they have a protective role is unknown. to dissect the protective function of trm cells, balb/c mice were infected with rsv; infected mice developed antigen-specific cd8(+) trm cells (cd103(+)/cd69(+)) in the lungs and airways. intranasally transferring cells from the airways of previou ...201728537249
macrophages produce il-33 by activating mapk signaling pathway during rsv infection.it has been reported that rsv infection can enhance il-33 production in lung macrophages. however, little is known about specific signaling pathways for activation of macrophages during rsv infection. in the present study, by using real-time rt-pcr as well as western blot assay, it became clear that rsv infection can enhance not only the expression of mrnas for mapk molecules (including p38, jnk1/2, and erk1/2), but also the levels of mapk proteins in lung macrophages as well as raw264.7 cells. ...201728531812
defining the vaccination window for respiratory syncytial virus (rsv) using age-seroprevalence data for children in kilifi, kenya.respiratory syncytial virus (rsv) is an important cause of lower respiratory tract disease in early life and a target for vaccine prevention. data on the age-prevalence of rsv specific antibodies will inform on optimizing vaccine delivery.201728531224
mitochondrial protein p32/hapb1/gc1qr/c1qbp is required for efficient respiratory syncytial virus production.respiratory syncytial virus (rsv) is a major cause of respiratory infections in infants and the elderly, leading to more deaths than influenza each year, but there is no antiviral or efficacious vaccine currently available. here we examine the role in infection of the host mitochondrial protein p32 (habp/gc1qr/c1qbp) for the first time. rsv replication as well as infectious virus production was significantly reduced by p32 sirna knockdown, consistent with an important role for p32 in rsv infecti ...201728576489
association of c-reactive protein with bacterial and respiratory syncytial virus-associated pneumonia among children aged <5 years in the perch study.lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of c-reactive protein (crp) for identifying bacterial pneumonia. we evaluated the sensitivity and specificity of crp for identifying bacterial vs respiratory syncytial virus (rsv) pneumonia in the pneumonia etiology research for child health (perch) multicenter case-control study.201728575375
respiratory syncytial virus: prospects for new and emerging therapeutics.respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infections (lrti) in infants, the elderly, and the immunocompromised. although the development of a rsv vaccine has been a priority for >50 years, there is still no vaccine available. treatment of rsv lrti has remained mostly supportive, i.e. hydration and oxygenation. palivizumab and ribavirin are the only options currently available for prevention and treatment of rsv infection, but evidence suggests that they are ...201728574729
efficacy and safety of ban huang oral liquid for treating bovine respiratory diseases.ban huang oral liquid was developed as a veterinary compound preparation by the lanzhou institute of husbandry and pharmaceutical sciences of the chinese academy of agricultural sciences (caas). the purpose of this study was to determine whether the oral liquid preparation of traditional chinese medicine, ban huang, is safe and effective for treating respiratory diseases in cattle.201728573221
a multi-laboratory study of diverse rsv neutralization assays indicates feasibility for harmonization with an international standard.a current barrier to the standardized evaluation of respiratory syncytial virus (rsv) vaccine candidates is the wide variety of virus neutralization assay formats currently in use for assessing immunogenicity. assay formats vary widely in labor intensiveness, duration, and sample throughput. furthermore, the cell lines and virus strains used are not consistent among formats. the purpose of this multi-laboratory study was to assess the variability across a diverse array of assay formats that quan ...201728476625
systematic review and meta-analysis of the efficacy and safety of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants.objective: to evaluate the effectiveness of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants. methods: four electronic databases (medline, embase, cinahl, and central) were searched from their inception to february 28, 2017 for studies involving infants aged less than 24 months with bronchiolitis which assessed the use of epinephrine and corticosteroid combination therapy. the methodological quality of the included studies was assessed using the cochrane collabo ...201728690542
parainfluenza virus 5 (piv5) expressing wild-type or pre-fusion respiratory syncytial virus (rsv) fusion protein protect mice and cotton rats from rsv challenge.human respiratory syncytial virus (rsv) is the leading cause of pediatric bronchiolitis and hospitalizations. rsv can also cause severe complications in elderly and immunocompromised individuals. there is no licensed vaccine. we previously generated a piv5-vectored vaccine candidate expressing the rsv fusion protein (f) that was immunogenic and protective in mice. in this work, our goal was to improve the original vaccine candidate by modifying the piv5 vector or by modifying the rsv-f antigen. ...201728747496
determining the burden of respiratory syncytial virus disease: the known and the unknown. 201728689665
impact of viral respiratory pathogens on outcomes after pediatric cardiac surgery.viral respiratory infection is commonly considered a relative contraindication to elective cardiac surgery. we aimed to determine the frequency and outcomes of symptomatic viral respiratory infection in pediatric cardiac surgical patients.201728114162
age-specific profiles of antibody responses against respiratory syncytial virus infection.respiratory syncytial virus (rsv) is one of the most prevalent causative agents of lower respiratory tract infections worldwide, especially in infants around 3 to 4months old. infants at such a young age have maternally-transferred passive antibodies against rsv but do not have active immune systems efficient enough for the control of rsv infection. in order to elucidate age-specific profiles of immune responses against rsv protection, antibody responses were examined by using blood samples in b ...201728111238
neutrophil subset responses in infants with severe viral respiratory infection.neutrophils are the predominant inflammatory cells recruited to the respiratory tract as part of the innate immune response to viral infections. recent reports indicate the existence of distinct functional neutrophil subsets in the circulatory compartment of adults, following severe inflammatory conditions. here, we evaluated the occurrence of neutrophil subsets in blood and broncho-alveolar lavage fluid during severe viral respiratory infection in infants based on cd16/cd62l expression. we show ...201728108365
recent sequence variation in probe binding site affected detection of respiratory syncytial virus group b by real-time rt-pcr.direct immuno-fluorescence test (ifat) and multiplex real-time rt-pcr have been central to rsv diagnosis in kilifi, kenya. recently, these two methods showed discrepancies with an increasing number of pcr undetectable rsv-b viruses.201728107671
c-jun n-terminal kinase activity is required for efficient respiratory syncytial virus production.respiratory syncytial virus (rsv) is a major cause of respiratory infections in infants and the elderly, leading to more deaths than influenza each year worldwide. with no rsv antiviral or efficacious vaccine currently available, improved understanding of the host-rsv interaction is urgently required. here we examine the contribution to rsv infection of the host stress-regulated c-jun n-terminal kinase (jnk), for the first time. peak jnk1/2 phosphoactivation is observed at ∼24 h post-infection, ...201728062184
respiratory syncytial virus. 201728030703
pulmonary hemorrhage as a complication of respiratory syncyntial virus (rsv) bronchiolitis.respiratory syncytial virus (rsv) is a common cause of bronchiolitis. although there are a number of recognized complications, pulmonary hemorrhage has not been reported previously. a retrospective case notes review was performed through an electronic search of a pediatric intensive care unit's medical records. seven patients with rsv infection and pulmonary hemorrhage were identified and included in this case series. six of the seven patients were born prematurely (30-36 weeks gestation). all p ...201728029754
prevalence of co-infection between respiratory syncytial virus and influenza in children.respiratory syncytial virus (rsv) and influenza have varying degree of seasonal overlap.201728012809
nasopharyngeal pneumococcal carriage during childhood community-acquired alveolar pneumonia: relationship between specific serotypes and coinfecting viruses.respiratory viruses and streptococcus pneumoniae are known to be copathogens in childhood pneumonia. however, it is unclear whether all pneumococcal serotypes are equally prone to such interaction. we attempted to determine association between carried pneumococcal serotypes and respiratory viruses during childhood community-acquired alveolar pneumonia (caap).201728011920
development of a global respiratory severity score for respiratory syncytial virus infection in infants.respiratory syncytial virus (rsv) infection in infants has recognizable clinical signs and symptoms. however, quantification of disease severity is difficult, and published scores remain problematic. thus, as part of a rsv pathogenesis study, we developed a global respiratory severity score (grss) as a research tool for evaluating infants with primary rsv infection.201728011907
respiratory syncytial virus infection-associated hospitalization rates in infants and children with cystic fibrosis.infections with respiratory syncytial virus (rsv) are the leading cause for hospital admissions in infants and young children. the incidence of rsv-related hospitalizations in patients with cystic fibrosis (cf) is unclear. to date, no effective treatment for rsv infections is available. thus, prophylaxis with the monoclonal antibody palivizumab is an important option.201728005688
estimating the burden of respiratory syncytial virus (rsv) on respiratory hospital admissions in children less than five years of age in england, 2007-2012.respiratory syncytial virus (rsv) is a leading cause of hospital admission in young children. with several rsv vaccines candidates undergoing clinical trials, recent estimates of rsv burden are required to provide a baseline for vaccine impact studies.201728058797
thymus activity measured by t-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is an important cause of hospitalization in previously healthy infants. immunological mechanisms predisposing infants to severe disease are poorly understood. early biomarkers for disease severity may assist clinical decisions. we investigated t-cell receptor excision circles (trec), episomal dna made during thymic t-cell receptor rearrangement, and a marker for thymus activity, both during disease and in neonatal screening cards as a risk factor for r ...201728056841
compassionate use experience with high-titer respiratory syncytical virus (rsv) immunoglobulin in rsv-infected immunocompromised persons.respiratory syncytial virus (rsv) may cause fatal lower respiratory tract infection (lrti) in immunocompromised patients. ribavirin with or without standard intravenous immunoglobulin (ivig) is frequently given although efficacy is debated. infusion of ivig with high levels of neutralizing antibody against rsv may offer benefit in these patients.201728054734
first versus second year respiratory syncytial virus prophylaxis in chronic lung disease (2005-2015).children aged <2 years with chronic lung disease (cld) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (rsvh) compared to healthy term infants. based on the updated position statements, we compared respiratory-related illness hospitalization (rih) and rsvh risks in cld children who received palivizumab during the first year (fy) versus second year (sy) of life in the canadian registry of palivizumab (caress). demographic data were collected at enrolment and ri ...201728105526
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