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rsv n-nanorings fused to palivizumab-targeted neutralizing epitope as a nanoparticle rsv vaccine.respiratory syncytial virus (rsv) is the leading cause of acute respiratory infections in children, yet no vaccine is available. the sole licensed preventive treatment against rsv is composed of a monoclonal neutralizing antibody (palivizumab), which targets a conformational epitope located on the fusion protein (f). palivizumab reduces the burden of bronchiolitis but does not prevent infection. thus, the development of rsv vaccines remains a priority. we previously evaluated nanorings formed by ...201727553073
stat6 inhibitory peptide given during rsv infection of neonatal mice reduces exacerbated airway responses upon adult reinfection.respiratory syncytial virus (rsv)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. early life rsv infection results in a th2-biased immune response, which is also typical of asthma. murine models of neonatal rsv infection have been developed to examine the possible contribution of rsv-driven th2 responses to the development of airway hyper-responsiveness later in childhood. we have investigated the ability of a cell-penetrating stat6 inhibi ...201727566834
respiratory and enteric virus detection in children.the majority of children with febrile seizures have viral infections and viruses were detected in 22% to 63% of children in published studies. using molecular methods, viruses were also detected in asymptomatic persons. a prospective study was conducted to detect respiratory and enteric viruses in 192 children with febrile seizures and compare the detection rates to those found in 156 healthy age-matched controls. a respiratory or enteric virus was detected in 72.9% of children with febrile seiz ...201727698149
in utero alcohol effects on foetal, neonatal and childhood lung disease.maternal alcohol use during pregnancy exposes both premature and term newborns to the toxicity of alcohol and its metabolites. foetal alcohol exposure adversely effects the lung. in contrast to the adult "alcoholic lung" phenotype, an inability to identify the newborn exposed to alcohol in utero has limited our understanding of its effect on adverse pulmonary outcomes. this paper will review advances in biomarker development of in utero alcohol exposure. we will highlight the current understandi ...201727613232
down syndrome as risk factor for respiratory syncytial virus hospitalization: a prospective multicenter epidemiological study.respiratory syncytial virus (rsv) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality.201727611835
analytical characterization of an oil-in-water adjuvant emulsion.adjuvants are typically used in subunit vaccine formulations to enhance immune responses elicited by individual antigens. physical chemical characterization of novel adjuvants is an important step in ensuring their effective use in vaccine formulations. this paper reports application of a panel of quantitative assays developed to analyze and characterize an oil-in-water adjuvant emulsion, which contains glucopyranosyl lipid a (gla) and is a squalene-based emulsion. gla is a fully synthetic analo ...201727628187
outcomes of infants receiving palivizumab prophylaxis for respiratory syncytial virus in canada and italy: an international, prospective cohort study.respiratory syncytial virus (rsv) infection frequently results in rsv-related hospitalization (rsvh) in young infants. we examined the outcomes of palivizumab recipients within the canadian registry (caress) and the torino-verona italian registry over the 2002-2014 rsv seasons.201727649365
drug candidates and model systems in respiratory syncytial virus antiviral drug discovery.the development of antiviral strategies to prevent or treat respiratory syncytial virus (rsv) infections is of great importance, especially considering the fact that rsv is one of the most important causes of pediatric respiratory infections. however, despite intense efforts, there is no antiviral or vaccine approved for the prevention or treatment of rsv infections. several inhibitors, targeting different rsv proteins have been discovered over the past decade. we here review the most important ...201727659812
bromodomain and extra terminal (bet) inhibitor suppresses macrophage-driven steroid-resistant exacerbations of airway hyper-responsiveness and inflammation.exacerbations of asthma are linked to significant decline in lung function and are often poorly controlled by corticosteroid treatment. clinical investigations indicate that viral and bacterial infections play crucial roles in the onset of steroid-resistant inflammation and airways hyperresponsiveness (ahr) that are hallmark features of exacerbations. we have previously shown that interferon γ (ifnγ) and lipopolysaccharide (lps) cooperatively activate pulmonary macrophages and induce steroid-res ...201727657907
seasonal variability of respiratory syncytial virus infection in the top end of the northern territory (2012-2014).to determine the prevalence of respiratory syncytial virus (rsv) in the top end of the northern territory and investigate potential drivers of seasonality including rainfall and humidex (humidity and heat index).201727671992
epidemiology, clinical characteristics, laboratory findings and severity of respiratory syncytial virus acute lower respiratory infection in malaysian children, 2008-2013.the aim of this study is to describe epidemiology, clinical features, laboratory data and severity of respiratory syncytial virus (rsv) acute lower respiratory infection (alri) in malaysian children and to determine risk factors associated with prolonged hospital stay, paediatric intensive care unit (picu) admission and mortality.201727704652
development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection.respiratory syncytial virus (rsv) remains a significant cause of morbidity and mortality in infants and young children, immunocompromised patients and the elderly. despite the high disease burden, an effective and safe vaccine is lacking, although several candidates are currently in development. current treatment for rsv infection remains largely supportive and rsv-specific options for prophylaxis are limited to palivizumab. in the past few years, novel therapeutic options including nanobodies, ...201727692523
potential cost-effectiveness of rsv vaccination of infants and pregnant women in turkey: an illustration based on bursa data.worldwide, respiratory syncytial virus (rsv) is considered to be the most important viral cause of respiratory morbidity and mortality among infants and young children. although no active vaccine is available on the market yet, there are several active vaccine development programs in various stages. to assess whether one of these vaccines might be a future asset for national immunization programs, modeling the costs and benefits of various vaccination strategies is needed.201727689356
the innate immune response to rsv: advances in our understanding of critical viral and host factors.respiratory syncytial virus (rsv) causes mild to severe respiratory illness in humans and is a major cause of hospitalizations of infants and the elderly. both the innate and the adaptive immune responses contribute to the control of rsv infection, but despite successful viral clearance, protective immunity against rsv re-infection is usually suboptimal and infections recur. poor understanding of the mechanisms limiting the induction of long-lasting immunity has delayed the development of an eff ...201727686836
respiratory syncytial virus hospitalization and mortality: systematic review and meta-analysis.respiratory syncytial virus (rsv) is a major public health burden worldwide. we aimed to review the current literature on the incidence and mortality of severe rsv in children globally.201727740723
detection of airborne respiratory syncytial virus in a pediatric acute care clinic.respiratory syncytial virus (rsv) is the most common cause of respiratory illness in infants and young children, but this virus is also capable of re-infecting adults throughout life. universal precautions to prevent its transmission consist of gown and glove use, but masks and goggles are not routinely required because it is believed that rsv is unlikely to be transmitted by the airborne route. our hypothesis was that rsv is present in respirable-size particles aerosolized by patients seen in a ...201727740722
the outpatient burden of respiratory syncytial virus infections in older children. 201727738053
clinical and socioeconomic burden of respiratory syncytial virus infection in children.vaccines and antivirals against respiratory syncytial virus (rsv) are being developed, but there are scarce data on the full impact of rsv infection on outpatient children.201727738052
the cost-effectiveness of palivizumab in infants with cystic fibrosis in the canadian setting: a decision analysis model.children with cystic fibrosis (cf) are at higher risk of severe respiratory syncytial virus (rsv) infection, which can lead to a decline in lung function. a monoclonal antibody, palivizumab (pmb), effectively prevents rsv hospitalizations; however, the high cost of pmb, approximately c$10,000 per patient per rsv season, limits its widespread use. we assess the cost-effectiveness of pmb prophylaxis in cf children less than 2 y of age from the canadian healthcare payer's perspective.201727768505
risk factors for virus-induced acute respiratory tract infections in children younger than 3 years and recurrent wheezing at 36 months follow-up after discharge.we sought to know more about how 14 common respiratory viruses manifest clinically, and to identify risk factors for specific virus-induced acute respiratory tract infections (artis) in children younger than 3 years old and for wheezing at 36-month follow-up.201727798551
a simple screening approach to prioritize genes for functional analysis identifies a role for interferon regulatory factor 7 in the control of respiratory syncytial virus disease.greater understanding of the functions of host gene products in response to infection is required. while many of these genes enable pathogen clearance, some enhance pathogen growth or contribute to disease symptoms. many studies have profiled transcriptomic and proteomic responses to infection, generating large data sets, but selecting targets for further study is challenging. here we propose a novel data-mining approach combining multiple heterogeneous data sets to prioritize genes for further ...201727822537
vitamin d increases the antiviral activity of bronchial epithelial cells in vitro.by modulating the antiviral immune response via vitamin d receptor, the active form of vitamin d (1,25-dihydroxyvitamin d, calcitriol) could play a central role in protection against respiratory virus infections. this in vitro study tested the hypothesis that respiratory viruses modulate vitamin d receptor expression in human bronchial epithelial cells and this modulation affects the antiviral response to exogenous vitamin d.201727838350
human newborn b cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus. 201727931976
burden of severe respiratory syncytial virus disease among 33-35 weeks' gestational age infants born during multiple respiratory syncytial virus seasons.moderate-late preterm infants, 33-35 weeks' gestational age (wga), are at increased risk for respiratory syncytial virus hospitalization (rsvh). the objective of this study is to quantify the burden of rsvh in moderate-late preterm infants.201727755464
chlorogenic compounds from coffee beans exert activity against respiratory viruses.chlorogenic acids are secondary metabolites in diverse plants. some chlorogenic acids extracted from traditional medicinal plants are known for their healing properties, e.g., against viral infections. also, green coffee beans are a rich source of chlorogenic acids, with 5-o-caffeoylquinic acid being the most abundant chlorogenic acid in coffee. we previously reported the synthesis of the regioisomers of lactones, bearing different substituents on the quinidic core. here, 3,4-o-dicaffeoyl-1,5-γ- ...201727806409
characterizing the risk of respiratory syncytial virus in infants with older siblings: a population-based birth cohort study.from a population-based birth cohort of 245 249 children born in western australia during 1996-2005, we used linkage of laboratory and birth record datasets to obtain data including all respiratory syncytial virus (rsv) detections during infancy from a subcohort of 87 981 singleton children born in the perth metropolitan area from 2000 to 2004. using log binomial regression, we found that the risk of infant rsv detection increases with the number of older siblings, with those having ⩾3 older sib ...201727821195
national evidence in israel supporting reevaluation of respiratory syncytial virus prophylactic guidelines.the american academy of pediatrics (aap) recently narrowed the indications for respiratory syncytial virus (rsv) prophylaxis, while in israel the guidelines have not changed.201727898422
pulmonary dendritic cell subsets shape the respiratory syncytial virus-specific cd8+ t cell immunodominance hierarchy in neonates.young infants are generally more susceptible to viral infections and experience more severe disease than do adults. cd8(+) t cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. using a murine cb6f1/j hybrid model of respiratory syncytial virus (rsv) infection, we previously demonstrated that the cd8(+) t cell immunodominance hierarchy to two rsv-derived epitopes, k(d)m282-90 and d(b)m187-195, was determined by the ...201727895172
respiratory syncytial virus and influenza are the key viral pathogens in children <2 years hospitalized with bronchiolitis and pneumonia in islamabad pakistan.pneumonia remains a leading cause of morbidity and mortality in developing countries. comprehensive surveillance data are needed to review the prevention and control strategies. we conducted active surveillance of acute lower respiratory infections among children aged <2 years hospitalized at two hospitals of islamabad, pakistan. viral etiology was determined using real-time pcr on respiratory specimens collected during march 2011-april 2012. the overall mean age was 7.83 ± 5.25 months while no ...201727885562
natural killer cells in asthma.this review article discusses current knowledge on natural killer (nk) cells in asthma.201727841766
immunopathogenesis associated with formaldehyde-inactivated rsv vaccine in preclinical and clinical studies.respiratory syncytial virus (rsv) infection is responsible for one-third of deaths of acute lower respiratory infection in children less than one-year-old. the formaldehyde-inactivated rsv vaccine trial conducted in the 1960s predisposed the vaccinees to more serious rsv infection instead of protection. better understanding of the underlying mechanism is of critical importance for better designing of safe and effective rsv vaccines. areas covered: pubmed was searched to review immunopathology in ...201727841687
predicting the relative impacts of maternal and neonatal respiratory syncytial virus (rsv) vaccine target product profiles: a consensus modelling approach.respiratory syncytial virus (rsv) is the major viral cause of infant and childhood lower respiratory tract disease worldwide. defining the optimal target product profile (tpp) is complicated due to a wide range of possible vaccine properties, modalities and an incomplete understanding of the mechanism of natural immunity. we report consensus population level impact projections based on two mathematical models applied to a low income setting.201727914740
factors predicting life-threatening infections with respiratory syncytial virus in adult patients.respiratory syncytial virus (rsv) is a significant cause of acute respiratory illness with a clinical spectrum ranging from self-limiting upper respiratory infection to severe lower respiratory infection in elderly persons as well as young children. however, there are limited data on risk factors for life-threatening infections that could guide the appropriate use of antiviral agents in adult patients with rsv.201727911143
molecular detection and characterization of respiratory syncytial virus b genotypes circulating in pakistani children.respiratory syncytial virus (rsv) is the major cause of acute lower respiratory tract infections in young children, but very little is known about its epidemiology and circulating genotypes in pakistan. this study analyzed the epidemiological and molecular characteristics of rsv b genotypes in pakistani children below 5years with acute respiratory tract infections (aris) during three consecutive winter seasons from 2010 to 2013. a total of 1941 samples were analyzed for rsv infection by real tim ...201727908797
a review on antiviral activity of the himalayan medicinal plants traditionally used to treat bronchitis and related symptoms.bronchitis is a common respiratory tract infection of humans mainly caused by influenza virus, rhinovirus, adenovirus, coronavirus and respiratory syncytial virus. the aim of this review was to gather fragmented literature on ethnomedicinal plants used against bronchitis in the himalayan region and their in-vitro validation against bronchitis causing viral pathogens.201727905101
respiratory syncytial virus: infection, detection, and new options for prevention and treatment.respiratory syncytial virus (rsv) infection is a significant cause of hospitalization of children in north america and one of the leading causes of death of infants less than 1 year of age worldwide, second only to malaria. despite its global impact on human health, there are relatively few therapeutic options available to prevent or treat rsv infection. paradoxically, there is a very large volume of information that is constantly being refined on rsv replication, the mechanisms of rsv-induced p ...201727903593
clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in france.the aim of this study was to analyse characteristics and outcome of respiratory syncytial virus (rsv) infection in adults hospitalized with influenza-like illness (ili).201727903461
impact of the updated guidance for palivizumab prophylaxis against respiratory syncytial virus infection: a single center experience.to determine the differences in number of respiratory syncytial virus (rsv) hospitalizations and outcomes in infants 29(0/7)-34(6/7) weeks' gestational age (wga) the season before (season 1 [s1]; 2013-2014) and after (season 2 [s2]; 2014-2015) implementation of the 2014 american academy of pediatrics revised guidance for palivizumab prophylaxis.201727855996
genetic modification of the lung directed toward treatment of human disease.genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (rsv) and pseudomonas, as well as pulmonary arterial hypertens ...201727927014
factors related to compliance with palivizumab prophylaxis for respiratory syncytial virus (rsv) infection - data from poland.to evaluate compliance and health outcomes in children receiving palivizumab prophylaxis and to identify factors that could impact parental compliance with the recommended regimen of palivizumab immunoprophylaxis.201727941187
development of bioluminescence imaging of respiratory syncytial virus (rsv) in virus-infected live mice and its use for evaluation of therapeutics and vaccines.respiratory syncytial virus (rsv) is one of the leading causes of pneumonia among infants with no human vaccine or efficient curative treatments. efforts are underway to develop new rsv vaccines and therapeutics. there is a dire need for animal models for preclinical evaluation and selection of products against rsv. herein, we developed a whole body bioluminescence imaging to follow replication of rsv a2 virus strain expressing firefly luciferase (rsva2-line19-ffl) in live balb/c mice that can b ...201727989627
virus-like particle vaccine by intranasal vaccination elicits protective immunity against respiratory syncytial viral infection in mice.respiratory syncytial virus (rsv) is a leading cause of lower respiratory infection in infants and children, but there is still no licensed vaccine available. in this report, we developed virus-like particle (vlp) vaccines based on the bac-to-bac baculovirus expression system, consisting of an influenza virus matrix (m1) protein and the rsv fusion protein (f) or glycoprotein (g). these rsv vlps were identified by western blot analysis and electron microscopy. female balb/c mice immunized intrana ...201727974288
monoclonal antibody against g glycoprotein increases respiratory syncytial virus clearance in vivo and prevents vaccine-enhanced diseases.respiratory syncytial virus (rsv) is a common cause of lower respiratory tract illness in infants, young children, and the elderly. the g glycoprotein plays a role in host cell attachment and also modulates the host immune response, thereby inducing disease pathogenesis. we generated two monoclonal antibodies (mabs; 5h6 and 3a5) against g protein core fragment (gcf), which consisted of amino acid residues 131 to 230 from rsv a2 g protein. epitope mapping study revealed that 5h6 specifically bind ...201728076422
defining the risk and associated morbidity and mortality of severe respiratory syncytial virus infection among infants with congenital heart disease.the regal (rsv evidence-a geographical archive of the literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (rsv) in western countries over the last 20 years. this fourth publication covers the risk and burden of rsv infection in infants with congenital heart disease (chd).201728070870
respiratory syncytial virus-induced paediatric ards: why we should unpack the syndrome. 201728000595
patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy.disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity.201728089873
respiratory syncytial virus bronchiolitis in children.bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (rsv) is the most common cause of this infection. rsv is transmitted through contact with respiratory droplets either directly from an infected person or self-inoculation by contaminated secretions on surfaces. patients with rsv bronchiolitis usually present with two to four days of upper respiratory tract symptoms such as fever, rhinorrhea, and congestion, followed by lower ...201728084708
respiratory syncytial virus associated hospitalizations in preterm infants of 29 to 32 weeks gestational age using a risk score tool for palivizumab prophylaxis.to evaluate the efficacy of palivizumab in infants of 29 to 32 weeks of gestational age (ga) based on a risk score tool developed for austria. retrospective single-center cohort study including all preterm infants of 29 (+0) to 32 (+6) weeks of ga born between 2004 and 2012 at a tertiary care university hospital. data on rsv-related hospitalizations over the first 2 years of life were analyzed and compared between those having received palivizumab and those without. the study population was comp ...201728078558
evaluation of alere i rsv for rapid detection of respiratory syncytial virus in children hospitalized with acute respiratory tract infection.alere i rsv is a novel rapid test which applies a nicking enzyme amplification reaction to detect respiratory syncytial virus in point-of-care settings. in this study, we evaluated the alere i rsv assay by using frozen nasopharyngeal swab samples that were collected in viral transport medium from children hospitalized with acute respiratory tract infection during the 2015-2016 winter season. alere i rsv assay results were compared to those for altona realstar rsv real-time reverse transcription- ...201728077700
brd4 couples nf-κb/rela with airway inflammation and the irf-rig-i amplification loop in respiratory syncytial virus infection.the airway mucosa expresses protective interferon (ifn) and inflammatory cytokines in response to respiratory syncytial virus (rsv) infection. in this study, we examine the role of bromodomain containing 4 (brd4) in mediating this innate immune response in human small airway epithelial cells. we observe that rsv induces brd4 to complex with nf-κb/rela. brd4 is functionally required for expression of the nf-κb-dependent inflammatory gene regulatory network (grn), including the ifn response factor ...201728077651
notch ligand delta-like 4 promotes regulatory t cell identity in pulmonary viral infection.regulatory t (treg) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. recent studies have shown that delta-like ligand 4 (dll4) was upregulated on apc after respiratory syncytial virus (rsv) infection, and its inhibition leads to exaggerated immunopathology. in the present study, we outline the role of dll4 in treg cell differentiation, stability, and function in rsv infection. we found that dll4 was expressed on cd11b( ...201728077598
effective use of oral ribavirin for respiratory syncytial viral infections in allogeneic haematopoietic stem cell transplant recipients.respiratory syncytial virus (rsv) is a frequent cause of respiratory viral infections, increasing the morbidity and mortality in allogeneic haematopoietic stem cell transplantation (hsct) recipients. little is known about the best management strategy in this immunocompromised group and there are very few data on oral ribavirin treatment.201728077243
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
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
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
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
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
human metapneumovirus and other respiratory viral infections during pregnancy and birth, nepal.human metapneumovirus (hmpv) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. the incidence and characteristics of hmpv have not been well described in pregnant women. as part of a trial of maternal influenza immunization in rural southern nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. during 2011-2014, hmpv was dete ...201728726613
prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus (rsv) infected infants.longitudinal rsv dynamics have not been well-studied despite existence of factors favoring prolonged rsv replication including: high mutation rates allowing rapid evolution and potential escape from immune control. we therefore measured viral load in previously rsv-naïve infants over prolonged time-spans.201728723886
a critical role of gas6/axl signal in allergic airway responses during rsv vaccine-enhanced disease.respiratory syncytial virus (rsv) is a common virus that causes lower respiratory infections across a wide range of ages. a licensed rsv vaccine is not available because vaccination with formalin-inactivated rsv (fi-rsv) and the subsequent rsv infection cause not only insufficient induction of neutralizing antibodies but also severe allergic airway responses, termed fi-rsv vaccine enhanced disease (fi-rsv ved). however, the underlying mechanism has not been identified, although a th2-biased immu ...201728722020
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
circadian transcription factor bmal1 regulates innate immunity against select rna viruses.bmal1 (brain and muscle arnt-like protein 1, also known as mop3 or arnt3) belongs to the family of the basic helix-loop-helix (bhlh)-pas domain-containing transcription factors, and is a key component of the molecular oscillator that generates circadian rhythms. here, we report that bmal1-deficient cells are significantly more susceptible to infection by two major respiratory viruses of the paramyxoviridae family, namely rsv and piv3. embryonic fibroblasts from bmal1(-/-) mice produced nearly 10 ...201727913791
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
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
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
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
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
[prediction of severe course in infants with rsv bronchiolitis under 6 months. spain].the need for mechanical ventilation (mv) in acute bronchiolitis (ab) by respiratory syncytial virus (rsv) varies depending on the series (6-18%). our goal is to determine the admissions to picu for mv in patients under 6 months with ab and define the risk factors for building a prediction model.201728104904
spread and evolution of respiratory syncytial virus a genotype on1, coastal kenya, 2010-2015.in february 2012, the novel respiratory syncytial virus (rsv) group a, genotype on1, was detected in kilifi county, coastal kenya. on1 is characterized by a 72-nt duplication within the highly variable g gene (encoding the immunogenic attachment surface protein). cases were diagnosed through surveillance of pneumonia in children at the county hospital. analysis of epidemiologic, clinical, and sequence data of rsv-a viruses detected over 5 rsv seasons (2010/2011 to 2014/2015) indicated the follow ...201728098528
conditioned medium from persistently rsv-infected macrophages alters transcriptional profile and inflammatory response of non-infected macrophages.cells susceptible to persistent viral infections undergo important changes in their biological functions as a consequence of the expression of viral gene products that are capable of altering the gene expression profile of the host cell. previously, we reported that persistence of the rsv genome in a mouse macrophage cell line induces important alterations in cell homeostasis, including constitutive expression of ifn-β and other pro-inflammatory cytokines. here, we postulated that changes in the ...201728069520
respiratory syncytial virus. 201728030703
hospitalizations for respiratory syncytial virus and vaccine-preventable infections in the first 2 years after pediatric liver transplant.to examine in liver transplant recipients at centers participating in the pediatric health information system dataset the number of hospitalizations for respiratory syncytial virus (rsv) and vaccine-preventable infections (vpis) in the first 2 years after transplantation, morbidity and mortality associated with these hospitalizations, and costs associated with these hospitalizations.201728088400
respiratory syncytial virus infection. 201728084715
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
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
thymic stromal lymphopoietin, il-33, and periostin in hospitalized infants with viral bronchiolitis.much attention has recently been focused on thymic stromal lymphopoietin (tslp), il-33, and periostin in allergic disease, but less is known about their role in viral bronchiolitis.the aim of the study was to investigate whether infants exhibit enhanced nasal airway secretion of tslp, il-33, and periostin during natural respiratory viral bronchiolitis compared to healthy controls.in total, 213 infants < 2 years of age, hospitalized with bronchiolitis from october/2013 to april/2016 were enrolled ...201728471975
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
burden and seasonality of viral acute respiratory tract infections among outpatients in southern sri lanka.in tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. we determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern sri lanka. from march 2013 to january 2015, we enrolled outpatients presenting with influenza-like illness (ili). nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex p ...201728719323
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
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
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
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
an interaction of lps and rsv infection in augmenting the ahr and airway inflammation in mice.respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract infection (lrti) in children under 5 years of age, especially infants with severe bronchiolitis. our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. in most cases, rsv-in ...201728695368
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
determining the burden of respiratory syncytial virus disease: the known and the unknown. 201728689665
respiratory viruses detected in mexican children younger than 5 years old with community-acquired pneumonia: a national multicenter study.acute respiratory infections are the leading cause of mortality in children worldwide, especially in developing countries. pneumonia accounts for 16% of all deaths of children under 5 years of age and was the cause of death of 935000 children in 2015. despite its frequency and severity, information regarding its etiology is limited. the aim of this study was to identify respiratory viruses associated with community-acquired pneumonia (cap) in children younger than 5 years old.201728673837
severity of pneumonia in under 5-year-old children from developing countries: a multicenter, prospective, observational study.pneumonia is the leading cause of death in children. the objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. a multicenter, observational study was conducted in five hospitals, from india (lucknow, vadu), madagascar (antananarivo), mali (bamako), and paraguay (san lorenzo). children aged 2-60 months wit ...201728719310
severe viral respiratory infections in children with ifih1 loss-of-function mutations.viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. to investigate a potential genetic cause, we recruited 120 previously healthy children requiring support in intensive care because of a severe illness caused by a respiratory virus. using exome and transcriptome sequencing, we identified and characterized three rare loss-of-function variants in ifih1, which encodes an rig-i-like receptor ...201728716935
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