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history and practice: antibodies in infectious diseases.antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with clostridium tetani and corynebacterium diphtheriae. however, after the discovery of penicillin by fleming in 1928, and the subsequent introduction of the much cheaper and safer antibiotics in the 1930s, serum therapy ...201526104697
human metapneumovirus.human metapneumovirus (hmpv), a paramyxovirus identified in 2001, is a leading cause of respiratory tract infections in both children and adults. seroprevalence studies demonstrate that the primary infection occurs before the age of 5 years, and humans are reinfected throughout life. the four subgroups of hmpv occur with year-to-year variability, and infection with one subgroup confers some serologic cross-protection. experimental vaccines elicit a humoral response in both animal and human model ...201426104361
prevention of respiratory syncytial virus infection: from vaccine to antibody.respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract disease in infants and young children. initial efforts to develop a vaccine to prevent rsv lower respiratory tract disease in children were halted because of serious adverse events that occurred when children were infected with rsv following vaccination, including vaccine-related deaths. subsequently, a major focus for researchers was to understand what led to these adverse events. investment in a vaccine for rsv c ...201426104207
vector-mediated in vivo antibody expression.this article focuses on a novel vaccine strategy known as vector-mediated antibody gene transfer, with a particular focus on human immunodeficiency virus (hiv). this strategy provides a solution to the problem of current vaccines that fail to generate neutralizing antibodies to prevent hiv-1 infection and aids. antibody gene transfer allows for predetermination of antibody affinity and specificity prior to "immunization" and avoids the need for an active humoral immune response against the hiv e ...201426104192
who consultation on respiratory syncytial virus vaccine development report from a world health organization meeting held on 23-24 march 2015.respiratory syncytial virus (rsv) is a globally prevalent cause of lower respiratory infection in neonates and infants. despite its disease burden, a safe and effective rsv vaccine has remained elusive. in recent years, improved understanding of rsv biology and innovations in immunogen design has resulted in the advancement of multiple vaccine candidates into the clinical development pipeline. given the growing number of vaccines in clinical trials, the rapid pace at which they are being tested, ...201626100926
comparison of the conventional multiplex rt-pcr, real time rt-pcr and luminex xtag® rvp fast assay for the detection of respiratory viruses.detection of respiratory viruses using polymerase chain reaction (pcr) is sensitive, specific and cost effective, having huge potential for patient management. in this study, the performance of an in-house developed conventional multiplex rt-pcr (mrt-pcr), real time rt-pcr (rtrt-pcr) and luminex xtag(®) rvp fast assay (luminex diagnostics, toronto, canada) for the detection of respiratory viruses was compared. a total 310 respiratory clinical specimens predominantly from pediatric patients, refe ...201626100490
human bocavirus infection as a cause of severe acute respiratory tract infection in children.in 2005 human bocavirus (hbov) was discovered in respiratory tract samples of children. the role of hbov as the single causative agent for respiratory tract infections remains unclear. detection of hbov in children with respiratory disease is frequently in combination with other viruses or bacteria. we set up an algorithm to study whether hbov alone can cause severe acute respiratory tract infection (sari) in children. the algorithm was developed to exclude cases with no other likely cause than ...201526100374
a cysteine zipper stabilizes a pre-fusion f glycoprotein vaccine for respiratory syncytial virus.recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. we recently developed a vaccine antigen against respiratory syncytial virus (rsv), which comprised the fusion (f) glycoprotein stabilized in its pre-fusion trimeric conformation by "ds-cav1" mutations and by an appended c-terminal trimerization motif or "foldon" from t4-bacteriophage fibritin. here we investigate the creation of a cysteine zipper to allow for the removal of the phag ...201526098893
molecular basis for the selective inhibition of respiratory syncytial virus rna polymerase by 2'-fluoro-4'-chloromethyl-cytidine triphosphate.respiratory syncytial virus (rsv) causes severe lower respiratory tract infections, yet no vaccines or effective therapeutics are available. als-8176 is a first-in-class nucleoside analog prodrug effective in rsv-infected adult volunteers, and currently under evaluation in hospitalized infants. here, we report the mechanism of inhibition and selectivity of als-8176 and its parent als-8112. als-8176 inhibited rsv replication in non-human primates, while als-8112 inhibited all strains of rsv in vi ...201526098424
multicenter evaluation of bd veritor system and rsv k-set for rapid detection of respiratory syncytial virus in a diagnostic laboratory setting.the recently introduced bd veritor system rsv laboratory kit (becton dickinson, sparks, md, usa) with automatic reading was evaluated and compared with the rsv k-set (coris bioconcept, gembloux, belgium) for the detection of respiratory syncytial virus (rsv) using 248 nasopharyngeal aspirates of children younger than 6 years old with respiratory tract infection. compared to reverse transcriptase polymerase chain reaction as gold standard, both tests had an identical sensitivity of 78.1% and a sp ...201526092509
impact of formulation and particle size on stability and immunogenicity of oil-in-water emulsion adjuvants.oil-in-water emulsions have gained consideration as vaccine adjuvants in recent years due to their ability to elicit a differentiated immunogenic response compared to traditional aluminum salt adjuvants. squalene, a cholesterol precursor, is a natural product with immunostimulatory properties, making it an ideal candidate for such oil-in-water emulsions. particle size is a key parameter of these emulsions and its relationship to stability and adjuvanticity has not been extensively studied. this ...201526090563
molecular viral epidemiology and clinical characterization of acute febrile respiratory infections in hospitalized children in taiwan.acute respiratory infection (ari) is a leading cause of morbidity and hospitalization in children. to profile the viruses causing ari in children admitted to a community-based hospital in central taiwan, a cross-sectional study was conducted on children under 14 years of age that were hospitalized with febrile ari. viral etiology was determined using conventional cell culture and a commercial respiratory virus panel fast assay (xtag rvp), capable of detecting 19 different respiratory viruses and ...201526089293
premature infants have impaired airway antiviral ifnγ responses to human metapneumovirus compared to respiratory syncytial virus.it is unknown why human metapneumovirus (hmpv) and respiratory syncytial virus (rsv) cause severe respiratory infection in children, particularly in premature infants. our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity.201526086642
partial attenuation of respiratory syncytial virus with a deletion of a small hydrophobic gene is associated with elevated interleukin-1β responses.the small hydrophobic (sh) gene of respiratory syncytial virus (rsv), a major cause of infant hospitalization, encodes a viroporin of unknown function. sh gene knockout virus (rsv δsh) is partially attenuated in vivo, but not in vitro, suggesting that the sh protein may have an immunomodulatory role. rsv δsh has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. we compared the immune response to infection w ...201526085154
rsv-induced h3k4 demethylase kdm5b leads to regulation of dendritic cell-derived innate cytokines and exacerbates pathogenesis in vivo.respiratory syncytial virus (rsv) infection can result in severe disease partially due to its ability to interfere with the initiation of th1 responses targeting the production of type i interferons (ifn) and promoting a th2 immune environment. epigenetic modulation of gene transcription has been shown to be important in regulating inflammatory pathways. rsv-infected bone marrow-derived dcs (bmdcs) upregulated expression of kdm5b/jarid1b h3k4 demethylase. kdm5b-specific sirna inhibition in bmdc ...201526083387
respiratory syncytial virus: more than a pediatric infection. 201526083298
plant-derived monoclonal antibodies for prevention and treatment of infectious disease.numerous monoclonal antibodies (mabs) that recognize and neutralize infectious pathogens have been isolated and developed over the years. the fact that infectious diseases can involve large populations of infected individuals is an important factor that has motivated the search for both cost-effective and scalable methods of antibody production. the current technologies for production of antibodies in plants allow for very rapid expression and evaluation that can also be readily scaled for multi ...201426082108
knowledge gaps on paediatric respiratory infections in morocco, northern africa.the burden of acute respiratory infections (ari) among moroccan children remains significant. however, scarce information is available regarding trends in its epidemiology and etiology, or regarding its associated prognostic factors. the purpose of this work was to review available data on the burden of ari among children under five years of age in morocco.201526078866
ten year retrospective evaluation of the seasonal distribution of agent viruses in childhood respiratory tract infections.infections caused by respiratory viruses sometimes occur as epidemias or pandemias and are an important public health problem in the whole world. these viral agents may lead to severe respiratory diseases especially in young children and in the elderly. the aim of this study was to determine the seasonal distribution of agent viruses in childhood respiratory infections in our region.201426078631
respiratory viruses associated with community-acquired pneumonia in children: matched case-control study.community-acquired pneumonia (cap) is the leading cause of death in children worldwide and a substantial proportion of childhood cap is caused by viruses. a better understanding of the role of virus infections in this condition is needed to improve clinical management and preventive measures. the aim of the study was therefore to assess the association between specific respiratory viruses and childhood cap.201526077969
efficacy and safety of laggera pterodonta in children 3-24 months with acute bronchiolitis: a randomized controlled trial.laggera pterodonta, a traditional chinese medicine, has been commonly used in respiratory tract infections for more than hundreds of years without any randomized controlled trials to evaluate its efficacy and safety.201726076757
biomarkers of respiratory syncytial virus (rsv) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity.despite fundamental advances in the research on respiratory syncytial virus (rsv) since its initial identification almost 60 years ago, recurring failures in developing vaccines and pharmacologic strategies effective in controlling the infection have allowed rsv to become a leading cause of global infant morbidity and mortality. indeed, the burden of this infection on families and health care organizations worldwide continues to escalate and its financial costs are growing. furthermore, strong e ...201526074450
ige anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma.respiratory syncytial virus (rsv) causes lower respiratory tract disease in infants and young children, and is a public health concern, as is the increase in pediatric asthma. respiratory viral infections may trigger asthma exacerbations. however, it remains unknown whether rsv infection may have a specific association with asthma. total serum ige, and ige- and igg-anti-rsv ab responses were studied in older asthmatic compared with non-asthmatic children (m/f, mean age: 14) (n=30, n=43, respecti ...201526074414
infants born before 32 weeks of gestation or with respiratory disease are most likely to receive palivizumab in the netherlands.palivizumab is reported to be effective in reducing respiratory syncytial virus hospitalisation. its licensed uses include infants younger than six months of age, born before 35 weeks of gestation or under two years old with congenital heart disease or bronchopulmonary dysplasia. we redressed lack of research in the netherlands by studying whether infants who met the licensed indications received the drug.201526073782
respiratory syncytial virus infection down-regulates antioxidant enzyme expression by triggering deacetylation-proteasomal degradation of nrf2.respiratory syncytial virus (rsv) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or treatment is available. rsv infection in cells, mice, and children leads to rapid generation of reactive oxygen species, which are associated with oxidative stress and lung damage, due to a significant decrease in the expression of airway antioxidant enzymes (aoes). oxidative stress plays an important role in the pathogenesis of rsv-i ...201526073125
respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness.exposure to chlorine (cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (ahr) to methacholine. however, little is known about the effect of preexisting respiratory disease on cl2-induced lung injury. by using a murine respiratory syncytial virus (rsv) infection model, we found that preexisting rsv infection increases cl2 (187 ppm for 30 min)-induced lung inflammation and airway ahr at 24 h after exposure (5 days after infection). rs ...201526071553
hypertonic saline for bronchiolitis in infants.recently, a 1-year-old patient returned from admission in the hospital for bronchiolitis, and the report i received indicated that he was treated with inhaled hypertonic saline, among other treatments. is this therapy recommended for children in the acute care setting?201526071156
oseltamivir in influenza outbreaks in care homes: challenges and benefits of use in the real world.respiratory virus infections, including influenza, are an important cause of potentially avoidable hospital admissions in the elderly. although recent reviews have questioned the efficacy of oseltamivir in the prevention of transmission, it has been a central part of the authors' strategy to manage outbreaks in residential homes.201526071039
novel antigens for rsv vaccines.respiratory syncytial virus (rsv) remains a leading global cause of infant mortality and adult morbidity. infection, which recurs throughout life, elicits only short-lived immunity. the development of a safe and efficacious vaccine has, thus far, been elusive. recent technological advances, however, have yielded promising rsv vaccine candidates that are based on solving atomic-level structures of surface glycoproteins interacting with neutralizing antibodies. the class i fusion glycoprotein, f, ...201526070108
respiratory syncytial virus in hematopoietic stem cell transplantation and solid-organ transplantation.respiratory syncytial virus (rsv), one of the most common causes of respiratory infections in immunocompetent individuals, can cause significant pulmonary morbidity and mortality in hematopoietic stem cell (hsct) and less often in solid-organ transplant recipients. early diagnosis and medical intervention prior to the progression from upper to lower respiratory tract viral involvement is essential to positively affect the clinical course. the greatest risk of disease progression from upper to lo ...201526068871
protein crystallography in vaccine research and development.the use of protein x-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. however, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. here, we review the important contributions that protein crystallography has made so far to vaccine research and development. we discuss several examples of the crystallographic characterization of vaccine antigen stru ...201526068237
eighteen years of respiratory syncytial virus surveillance: changes in seasonality and hospitalization rates in southwestern alaska native children.alaska native infants from the yukon-kuskokwim delta (ykd) experienced respiratory syncytial virus (rsv) hospitalization rates 5 times higher and an rsv season twice as long as the general us infant population. we describe trends in hospitalization rates and seasonality during 18 years of continuous rsv surveillance in this population and explore contributions of climate and sociodemographic factors.201526065863
immunological, viral, environmental, and individual factors modulating lung immune response to respiratory syncytial virus.respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high risk infants and adults. several studies have been performed to investigate the immune response that determines the clinical course of the infection. in the present paper, we review the literature on viral, environmental, and host factors influencing virus response; the mechanisms of the immune response; and the action of nonimmunol ...201526064963
novel antiviral activity of mung bean sprouts against respiratory syncytial virus and herpes simplex virus -1: an in vitro study on virally infected vero and mrc-5 cell lines.new sources for discovering novel antiviral agents are desperately needed. the current antiviral products are both expensive and not very effective.201526062546
trends of respiratory syncytial virus infections in children under 2 years of age in puerto rico.the respiratory syncytial virus (rsv) is the most significant viral pathogen causing bronchiolitis and pneumonia in infants, today. in tropical climates the rsv infection may occur throughout the year. the purpose of this study was to asses rsv infections during the 2009‒2010 rsv season in children under 2 years of age and to evaluate the trend of positive rsv tests in the period of 2007 to 2009.201526061061
adult patients with respiratory syncytial virus infection: impact of solid organ and hematopoietic stem cell transplantation on outcomes.respiratory syncytial virus (rsv) is a common community-acquired pathogen responsible for a substantial disease burden in adults. we investigated the outcomes after rsv infection in hospitalized adults over a 3-year period.201526059180
the danish national prescription registry in studies of a biological pharmaceutical: palivizumab - validation against two external data sources.national prescription databases are important tools in pharmacoepidemiological studies investigating potential long-term adverse events after drug use. palivizumab is a biological pharmaceutical used as passive prophylaxis against severe infection with respiratory syncytial virus in high-risk children.201526056490
the role of phosphodiesterase 12 (pde12) as a negative regulator of the innate immune response and the discovery of antiviral inhibitors.2',5'-oligoadenylate synthetase (oas) enzymes and rnase-l constitute a major effector arm of interferon (ifn)-mediated antiviral defense. oas produces a unique oligonucleotide second messenger, 2',5'-oligoadenylate (2-5a), that binds and activates rnase-l. this pathway is down-regulated by virus- and host-encoded enzymes that degrade 2-5a. phosphodiesterase 12 (pde12) was the first cellular 2-5a- degrading enzyme to be purified and described at a molecular level. inhibition of pde12 may up-regul ...201526055709
antiviral efficacy of a respiratory syncytial virus (rsv) fusion inhibitor in a bovine model of rsv infection.respiratory syncytial virus (rsv) is the leading cause of bronchiolitis and pneumonia in infants. effective treatment for rsv infection is a significant unmet medical need. while new rsv therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human rsv, making it difficult to evaluate new disease interventions. experimental infection of holstein calves with bovine rsv (brsv) causes a severe respiratory infection that is similar to human rsv infection, ...201526055364
protein-protein interactions of viroporins in coronaviruses and paramyxoviruses: new targets for antivirals?viroporins are members of a rapidly growing family of channel-forming small polypeptides found in viruses. the present review will be focused on recent structural and protein-protein interaction information involving two viroporins found in enveloped viruses that target the respiratory tract; (i) the envelope protein in coronaviruses and (ii) the small hydrophobic protein in paramyxoviruses. deletion of these two viroporins leads to viral attenuation in vivo, whereas data from cell culture shows ...201526053927
influenza-attributable deaths in south-eastern france (1999 to 2010): mortality predictions were undependable.following the 2009 influenza pandemic, several studies showed that the mortality pattern associated with the a(h1n1)2009 virus primarily affected children and young adults. in this study, we aimed to estimate the influenza-attributable deaths during the periods from 1999 to 2010, in the provence-alpes-côte-d'azur (paca) region of south-eastern france in order to corroborate the hypothesis that (i) influenza-attributable deaths caused by a(h1n1)2009 strain were much lower than initially expected.201526049715
characteristics and their clinical relevance of respiratory syncytial virus types and genotypes circulating in northern italy in five consecutive winter seasons.in order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (rsv) and their possible relationships with the severity of rsv infection, we studied all of the rsv-positive nasopharyngeal samples collected from children during five consecutive winters (2009-2010, 2010-2011, 2011-2012, 2012-2013 and 2013-2014). the rsvs were detected using the respiratory virus panel fast assay and single-tube rt-pcr, their nucleotides were sequenced, and ...201526047100
natural helper cells contribute to pulmonary eosinophilia by producing il-13 via il-33/st2 pathway in a murine model of respiratory syncytial virus infection.it has been reported that natural helper cells, which are a non-t, non-b innate lymphoid cell type expressing c-kit and st2, mediate influenza-induced airway hyper-reactivity by producing substantial il-13. however, little is known about natural helper cells for the development of rsv-induced airway inflammation, particularly eosinophilic infiltration. by using balb/c mice that were infected intranasally with rsv, it became clear that infection with rsv can induce an increase in the absolute num ...201526044350
resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice.respiratory syncytial virus (rsv) infection is involved in persistent and recurrent wheezing. there are no effective and safe drugs for the sequelae of persistent wheezing after early bronchiolitis. in this study, we investigated the effect of resveratrol on persistent airway inflammation and airway hyperresponsiveness (ahr) induced by rsv infection. rsv-infected mice were sacrificed at serial time points after infection to collect samples and measure the number of inflammatory cells and levels ...201526044349
emerging human respiratory syncytial virus genotype on1 found in infants with pneumonia in beijing, china. 201326038462
incidence, risk factors and hospital burden in children under five years of age hospitalised with respiratory syncytial virus infections.respiratory syncytial virus (rsv) infections are among the most common lower respiratory tract infections in infants, but few studies have determined the age-specific incidence of hospitalisation in defined populations. this study gathered swedish data on rsv in gothenburg and its 10 surrounding municipalities from 2004 to 2011.201526036725
modulation of the immune response to respiratory viruses by vitamin d.vitamin d deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ari) in a number of observational studies, and meta-analysis of clinical trials of vitamin d supplementation for prevention of ari has demonstrated protective effects. several cellular studies have investigated the effects of vitamin d metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking.201526035247
the paramyxovirus polymerase complex as a target for next-generation anti-paramyxovirus therapeutics.the paramyxovirus family includes major human and animal pathogens, including measles virus, mumps virus, and human respiratory syncytial virus (rsv), as well as the emerging zoonotic hendra and nipah viruses. in the u.s., rsv is the leading cause of infant hospitalizations due to viral infectious disease. despite their clinical significance, effective drugs for the improved management of paramyxovirus disease are lacking. the development of novel anti-paramyxovirus therapeutics is therefore urg ...201526029193
inflammatory damage on respiratory and nervous systems due to hrsv infection.the exacerbated inflammatory response elicited by human respiratory syncytial virus (hrsv) in the lungs of infected patients causes a major health burden in the pediatric and elderly population. since the discovery of hrsv, the exacerbated host immune-inflammatory response triggered by this virus has been extensively studied. in this article, we review the effects on the airways caused by immune cells and cytokines/chemokines secreted during hrsv infection. while molecules such as interferons co ...201526026788
objectives, design and enrollment results from the infant susceptibility to pulmonary infections and asthma following rsv exposure study (inspire).respiratory syncytial virus (rsv) lower respiratory tract infection (lri) during infancy has been consistently associated with an increased risk of childhood asthma. in addition, evidence supports that this relationship is causal. however, the mechanisms through which rsv contributes to asthma development are not understood. the inspire (infant susceptibility to pulmonary infections and asthma following rsv exposure) study objectives are to: 1) characterize the host phenotypic response to rsv in ...201526021723
respiratory syncytial virus bronchiolitis in children up to 5 years of age in spain: epidemiology and comorbidities: an observational study.this epidemiological survey in spain estimates the burden of respiratory syncytial virus (rsv) infection in children up to 5 year of age during a 15-year period (1997-2011). observational retrospective survey was conducted by reviewing data of the national surveillance system for hospital data, including >98% of spanish hospitals. all hospitalizations related to rsv infection for children up to 5 years, reported during 1997-2011 period, were analyzed. codes were selected by using the internation ...201526020386
functional analysis of the 60-nucleotide duplication in the respiratory syncytial virus buenos aires strain attachment glycoprotein.there are two subgroups of respiratory syncytial virus (rsv), a and b, and within each subgroup, isolates are further divided into clades. several years ago, multiple subgroup b isolates which contained a duplication of 60 nucleotides in the glycoprotein (g) gene were described. these isolates were given a new clade designation of ba based on the site of isolation, buenos aires, argentina. ba rsv strains have since become the predominant circulating clade of rsv b viruses. we hypothesized that t ...201526018171
nonglycosylated g-protein vaccine protects against homologous and heterologous respiratory syncytial virus (rsv) challenge, while glycosylated g enhances rsv lung pathology and cytokine levels.new efforts are under way to develop a vaccine against respiratory syncytial virus (rsv) that will provide protective immunity without the potential for vaccine-associated disease enhancement such as that observed in infants following vaccination with formalin-inactivated rsv vaccine. in addition to the f fusion protein, the g attachment surface protein is a target for neutralizing antibodies and thus represents an important vaccine candidate. however, glycosylated g protein expressed in mammali ...201526018164
mucosal delivery of a vectored rsv vaccine is safe and elicits protective immunity in rodents and nonhuman primates.respiratory syncytial virus (rsv) is a leading cause of severe respiratory disease in infants and the elderly. no vaccine is presently available to address this major unmet medical need. we generated a new genetic vaccine based on chimpanzee adenovirus (panad3-rsv) and modified vaccinia ankara rsv (mva-rsv) encoding the f, n, and m2-1 proteins of rsv, for the induction of neutralizing antibodies and broad cellular immunity. because rsv infection is restricted to the respiratory tract, we compare ...201526015988
[prevalence of respiratory syncytial virus infection in hospitalized children at a children's hospital and effects of climate change on the prevalence in suzhou, china].to investigate the prevalence of respiratory syncytial virus (rsv) infection in hospitalized children and the relationship between the prevalence and the climate change in suzhou, china.201526014700
antiviral activity of tmc353121, a respiratory syncytial virus (rsv) fusion inhibitor, in a non-human primate model.the study assessed the antiviral activity of tmc353121, a respiratory syncytial virus (rsv) fusion inhibitor, in a preclinical non-human primate challenge model with a viral shedding pattern similar to that seen in humans, following continuous infusion (ci).201526010881
risk factors for bronchiolitis hospitalization during the first year of life in a multicenter italian birth cohort.respiratory syncytial virus (rsv) is one of the main causes of respiratory infections during the first year of life. very premature infants may contract more severe diseases and 'late preterm infants' may also be more susceptible to the infection. the aim of this study is to evaluate the risk factors for hospitalization during the first year of life in children born at different gestational ages in italy.201526006025
conservation of g-protein epitopes in respiratory syncytial virus (group a) despite broad genetic diversity: is antibody selection involved in virus evolution?worldwide g-glycoprotein phylogeny of human respiratory syncytial virus (hrsv) group a sequences revealed diversification in major clades and genotypes over more than 50 years of recorded history. multiple genotypes cocirculated during prolonged periods of time, but recent dominance of the ga2 genotype was noticed in several studies, and it is highlighted here with sequences from viruses circulating recently in spain and panama. reactivity of group a viruses with monoclonal antibodies (mabs) tha ...201525995258
respiratory syncytial virus inhibitor az-27 differentially inhibits different polymerase activities at the promoter.respiratory syncytial virus (rsv) is the leading cause of pediatric respiratory disease. rsv has an rna-dependent rna polymerase that transcribes and replicates the viral negative-sense rna genome. the large polymerase subunit (l) has multiple enzymatic activities, having the capability to synthesize rna and add and methylate a cap on each of the viral mrnas. previous studies (h. xiong et al., bioorg med chem lett, 23:6789-6793, 2013, http://dx.doi.org/10.1016/j.bmcl.2013.10.018; c. l. tiong-yip ...201525995255
viral respiratory infections of adults in the intensive care unit.viral lower respiratory tract infections (lrtis) are an underappreciated cause of critical illness in adults. recent advances in viral detection techniques over the past decade have demonstrated viral lrtis are associated with rates of morbidity, mortality, and health care utilization comparable to those of seen with bacterial community acquired and nosocomial pneumonias. in this review, we describe the relationship between viral lrtis and critical illness, as well as discuss relevant clinical f ...201625990273
nk cell immunophenotypic and genotypic analysis of infants with severe respiratory syncytial virus infection.respiratory syncytial virus (rsv) is the leading cause of severe lower respiratory tract infection in infants. reduced numbers of nk cells have been reported in infants with severe rsv infection; however, the precise role of nk cells during acute rsv infection is unclear. in this study the nk and t cell phenotypes, lilrb1 gene polymorphisms and kir genotypes of infants hospitalized with rsv infection were analyzed. compared to controls, infants with acute rsv infection showed a higher proportion ...201525988502
3d tissue-like assemblies: a novel approach to investigate virus-cell interactions.virus-host cell interactions are most commonly analyzed in cells maintained in vitro as two-dimensional tissue cultures. however, these in vitro conditions vary quite drastically from the tissues that are commonly infected in vivo. over the years, a number of systems have been developed that allow the establishment of three-dimensional (3d) tissue structures that have properties similar to their in vivo 3d counterparts. these 3d systems have numerous applications including drug testing, maintena ...201525986169
age-specific epidemic waves of influenza and respiratory syncytial virus in a subtropical city.both influenza and respiratory syncytial virus (rsv) are active throughout the year in subtropical or tropical regions, but few studies have reported on age-specific seasonal patterns of these viruses. we examined the age-specific epidemic curves of laboratory-confirmed cases of influenza a (subtyped into seasonal a(h1n1), a(h3n2), and pandemic virus a(h1n1)pdm09), influenza b and respiratory syncytial virus (rsv), in subtropical city hong kong from 2004 to 2013. we found that different types an ...201525981824
estimating the hospitalization burden associated with influenza and respiratory syncytial virus in new york city, 2003-2011.hospitalization burden associated with influenza and respiratory syncytial virus (rsv) is uncertain due to ambiguity in the inference methodologies employed for its estimation.201525980600
discovery of β-d-2'-deoxy-2'-α-fluoro-4'-α-cyano-5-aza-7,9-dideaza adenosine as a potent nucleoside inhibitor of respiratory syncytial virus with excellent selectivity over mitochondrial rna and dna polymerases.novel 4'-substituted β-d-2'-deoxy-2'-α-fluoro (2'd2'f) nucleoside inhibitors of respiratory syncytial virus (rsv) are reported. the introduction of 4'-substitution onto 2'd2'f nucleoside analogs resulted in compounds demonstrating potent cell based rsv inhibition, improved inhibition of the rsv polymerase by the nucleoside triphosphate metabolites, and enhanced selectivity over incorporation by mitochondrial rna and dna polymerases. selectivity over the mitochondrial polymerases was found to be ...201525978965
differential mucin expression by respiratory syncytial virus and human metapneumovirus infection in human epithelial cells.mucins (muc) constitute an important component of the inflammatory and innate immune response. however, the expression of these molecules by respiratory viral infections is still largely unknown. respiratory syncytial virus (rsv) and human metapneumovirus (hmpv) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. currently, there is not vaccine available for neither virus. in this work, we explored the differential ex ...201525977598
effect of preexisting serum and mucosal antibody on experimental respiratory syncytial virus (rsv) challenge and infection of adults.we studied preexisting respiratory syncytial virus (rsv)-specific serum and nasal antibodies and their correlation with infectivity, viral dynamics, and disease severity in a human experimental infection model. higher preinoculation serum neutralizing antibody titers and nasal immunoglobulin (ig) a predicted lower infectivity and lower measures of viral replication. however, once individuals were infected, no significant protective effect of preexisting antibodies was seen. lack of correlation b ...201525977264
etiological role of ortho- and paramyxoviruses in acute respiratory tract infections among children aged < 4 years in bulgaria.influenza viruses (family orthomyxoviridae); respiratory-syncytial virus (rsv), human metapneumovirus (hmpv), and parainfluenza viruses (hpiv) type 1, 2 and 3 (family paramyxoviridae) are among the most common causes of acute respiratory tract infections (arti) in infants and young children. the aim of this study was to determine the contribution of these viruses in cases of arti requiring medical attention among children aged < 4 years during the 2012/13 and 2013/14 winter seasons in bulgaria.201525974986
association of respiratory viruses with outcomes of severe childhood pneumonia in botswana.the highest incidence of childhood acute lower respiratory tract infection (alri) is in low- and middle-income countries. few studies examined whether detection of respiratory viruses predicts alri outcomes in these settings.201525973924
respiratory syncytial virus infection upregulates nlrc5 and major histocompatibility complex class i expression through rig-i induction in airway epithelial cells.respiratory syncytial virus (rsv) is the leading cause of acute respiratory tract viral infection in infants, causing bronchiolitis and pneumonia. the host antiviral response to rsv acts via retinoic acid-inducible gene i (rig-i). we show here that rsv infection upregulates major histocompatibility complex class i (mhc-i) expression through the induction of nlrc5, a nod-like, card domain-containing intracellular protein that has recently been identified as a class i mhc transactivator (cita). rs ...201525972545
what we have learned from the influenza a ph1n1 2009/10 pandemic: high clinical impact of human metapneumovirus and respiratory syncytial virus in hospitalized pediatric patients.the influenza pandemic in 2009/2010 shifted public awareness to respiratory tract infections caused by the influenza virus. a prospective study was conducted during the influenza pandemic from november 2009 through april 2010 to determine the causative pathogens and clinical symptoms present in all children and adolescents admitted to the university children's hospital, duesseldorf, germany, with signs and symptoms of respiratory tract infection. a total of 272 children and adolescents were admi ...201625971322
streptococcus pneumoniae enhances human respiratory syncytial virus infection in vitro and in vivo.human respiratory syncytial virus (hrsv) and streptococcus pneumoniae are important causative agents of respiratory tract infections. both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. it has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. however, studies on the influence of bacterial ...201525970287
an anti-g protein monoclonal antibody treats rsv disease more effectively than an anti-f monoclonal antibody in balb/c mice.respiratory syncytial virus (rsv) belongs to the family paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. to clarify the potential for an anti-g mab, 131-2g which has both anti-viral and anti-inflammatory effects, to effectively treat rsv disease, we determined the kinetics of its effect compared to the effect of the anti-f mab, 143-6c on disease in mice. treatment adm ...201525965801
population-based incidence and etiology of community-acquired neonatal viral infections in bangladesh: a community-based and hospital-based surveillance study.the etiology of >90% of cases of suspected neonatal infection remains unknown. we conducted community-based surveillance in conjunction with hospital-based surveillance in a rural region in bangladesh from june 2006 to september 2007 to assess the incidence and etiology of community-acquired viral infections among neonates.201525961894
blocking respiratory syncytial virus entry: a story with twists.respiratory syncytial virus (rsv) is responsible for majority of infant hospitalizations due to viral infections. despite its clinical importance, no vaccine against rsv or effective antiviral therapy is available. several structural classes of small-molecule rsv entry inhibitor have been described and one compound has advanced to clinical testing. mutations in either one of two resistance hot spots in the f protein mediate unusual pan-resistance to all of these inhibitor classes. based on the b ...201525961744
review of non-bacterial infections in respiratory medicine: viral pneumonia.although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. the clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not general ...201525957460
respiratory syncytial virus as a cause of acute respiratory infections in adults. an emerging disease? 201525956018
long-term burden and respiratory effects of respiratory syncytial virus hospitalization in preterm infants-the spring study.the health status of premature infants born 321-350 weeks' gestational age (wga) hospitalized for rsv infection in the first year of life (cases; n = 125) was compared to that of premature infants not hospitalized for rsv (controls; n = 362) through 6 years. the primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. a significantly hig ...201525955487
three-weekly doses of azithromycin for indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial.bronchiolitis is a major health burden in infants globally, particularly among indigenous populations. it is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. in an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in indigenous infants hospitalized with bronchiolitis.201525954737
what is the added benefit of oropharyngeal swabs compared to nasal swabs alone for respiratory virus detection in hospitalized children aged <10 years?we evaluated the added value of collecting both nasal and oropharyngeal swabs, compared with collection of nasal swabs alone, for detection of common respiratory viruses by reverse transcription-polymerase chain reaction in hospitalized children aged <10 years. nasal swabs had equal or greater sensitivity than oropharyngeal swabs for detection of respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus, and influenza virus but not parainfluenza virus. the addition of an orophar ...201525943205
discovery of imidazopyridine derivatives as highly potent respiratory syncytial virus fusion inhibitors.a series of imidazolepyridine derivatives were designed and synthesized according to the established docking studies. the imidazopyridine derivatives were found to have good potency and physical-chemical properties. several highly potent compounds such as 8ji, 8jl, and 8jm were identified with single nanomolar activities. the most potent compound 8jm showed an ic50 of 3 nm, lower microsome clearance and no cyp inhibition. the profile of 8jm appeared to be superior to bms433771, and supported fur ...201525941547
frequent asymptomatic respiratory syncytial virus infections during an epidemic in a rural kenyan household cohort.the characteristics, determinants, and potential contribution to transmission of asymptomatic cases of respiratory syncytial virus (rsv) infection have not been well described.201525941331
inhibition of respiratory syncytial virus replication and virus-induced p38 kinase activity by berberine.respiratory syncytial virus (rsv) causes severe lower respiratory tract infection and poses a major public health threat worldwide. no effective vaccines or therapeutics are currently available; berberine, an isoquinoline alkaloid from various medicinal plants, has been shown to exert antiviral and several other biological effects. recent studies have shown that p38 mitogen-activated protein kinase (mapk) activity is implicated in infection by and replication of viruses such as rsv and the influ ...201525939536
rsv p-protein impairs extrinsic apoptosis pathway in a macrophage-like cell line persistently infected with respiratory syncytial virus.disabling apoptosis is practically a mandatory step for establishing and maintaining viral persistence in host cells. thus, persisting viruses have evolved strategies to impair apoptosis mechanisms. apoptosis can be induced through either the intrinsic or the extrinsic pathway. previously, we reported that staurosporine-induced intrinsic apoptotic pathway was down-regulated in a macrophage cell line persistently infected with respiratory syncytial virus (rsv, mφp). in the present study, our resu ...201525937519
prediction of respiratory disease and diarrhea in veal calves based on immunoglobulin levels and the serostatus for respiratory pathogens measured at arrival.failure of passive transfer is a common problem in calves destined for veal production. at present it is unknown whether the risk for respiratory disease (brd) or neonatal calf diarrhea (ncd) in the veal herd is associated with total immunoglobulin (ig) and/or on the serostatus for respiratory pathogens measured at arrival. therefore, the first objective of this prospective longitudinal cohort study was to determine associations between serum protein fractions as determined by routine electropho ...201525937168
detection of adenovirus and respiratory syncytial virus in patients with chronic obstructive pulmonary disease: exacerbation versus stable condition.latent infection with adenovirus and respiratory syncytial virus (rsv) is associated with chronic obstructive pulmonary disease (copd). the role of respiratory viral infections are emerging in copd exacerbations. the present study aimed to investigate the prevalence of adenovirus and rsv serotypes a and b in individuals with acute exacerbations of copd (copd-ae) and stable copd. twenty seven patients with copd-ae were evaluated using a prospective longitudinal study design. induced sputum, sera ...201525936369
protection conferred by virus-like particle vaccines against respiratory syncytial virus infection in mice by intranasal vaccination.respiratory syncytial virus (rsv) is a major pathogen in infants and the elderly, causing pneumonia and bronchiolitis. despite decades of research, to date there is still no approved rsv vaccine available. in this study, we developed rsv virus-like particle (vlp) vaccines containing an rsv fusion (f) and/or attachment (g) protein with newcastle disease virus (ndv) as the platform. the vlps were expressed in a baculovirus system and purified by sucrose gradient centrifugation. balb/c mice immuniz ...201525933187
addressing a challenge with a challenge. investigating respiratory syncytial virus immunity with the human challenge model. 201525932761
respiratory syncytial virus in children with influenza-like illness. 201525929636
rapid replacement of prevailing genotype of human respiratory syncytial virus by genotype on1 in beijing, 2012-2014.human respiratory syncytial virus (hrsv) is the most common viral pathogen causing lower respiratory infections in infants and young children worldwide. hrsv on1 genotype in subgroup a with a characteristic of a 72 nucleotide duplication in the second highly variable region of attachment glycoprotein gene, has been reported in some countries since it was first detected in clinical samples collected in canada in 2010. in this study, 557 hrsv antigen-positive nasopharyngeal aspirates were randomly ...201525929164
structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.bovine respiratory disease (brd) is an economically important disease of cattle and continues to be an intensely studied topic. however, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. a structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common brd viral and bacterial pathog ...201725929158
impact of the 2009 h1n1 pandemic on age-specific epidemic curves of other respiratory viruses: a comparison of pre-pandemic, pandemic and post-pandemic periods in a subtropical city.the 2009 h1n1 influenza pandemic caused offseason peaks in temperate regions but coincided with the summer epidemic of seasonal influenza and other common respiratory viruses in subtropical hong kong. this study was aimed to investigate the impact of the pandemic on age-specific epidemic curves of other respiratory viruses.201525928217
the nectin-4/afadin protein complex and intercellular membrane pores contribute to rapid spread of measles virus in primary human airway epithelia.the discovery that measles virus (mv) uses the adherens junction protein nectin-4 as its epithelial receptor provides a new vantage point from which to characterize its rapid spread in the airway epithelium. we show here that in well-differentiated primary cultures of airway epithelial cells from human donors (hae), mv infectious centers form rapidly and become larger than those of other respiratory pathogens: human respiratory syncytial virus, parainfluenza virus 5, and sendai virus. while visi ...201525926640
clinical and virological characteristics of early and moderate preterm infants readmitted with viral respiratory infections.rehospitalization of children born prematurely (referred to as preterm children) caused by severe respiratory infections is common. most studies have focused on respiratory syncytial virus infection. we designed a study to determine the virological and clinical characteristics of severe respiratory infections of children born early (<32 weeks) and moderate preterm (32 to 36 weeks), and compared them with full term (ft; ≥37 weeks) children who were subsequently admitted with respiratory illness.201525923427
caspase-1 independent viral clearance and adaptive immunity against mucosal respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is recognized by the innate immune system through toll like receptors (tlrs) and retinoic acid inducible gene i. these pathways lead to the activation of type i interferons and resistance to infection. in contrast to tlrs, very few studies have examined the role of nod-like receptors in viral recognition and induction of adaptive immune responses to rsv. caspase-1 plays an essential role in the immune response via the maturation of the proinflammatory ...201525922596
computerized assessment of wheezing in children with respiratory syncytial virus bronchiolitis before and after hypertonic saline nebulization.studies suggest an effect of nebulized hypertonic saline solution on air-flow limitation in subjects with respiratory syncytial virus (rsv) bronchiolitis, but results are based on subjective scores of clinical severity and are not clear. in this observational study, we used a noninvasive computerized tool to quantify wheezing before and after nebulization with hypertonic saline in children admitted for rsv infection.201525922547
parainfluenza virus as a cause of acute respiratory infection in hospitalized children.human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children.201525922290
new options in the treatment of respiratory syncytial virus disease.respiratory syncytial virus (rsv) remains a significant cause of morbidity and mortality in infants, immunocompromised patients and the elderly. despite the high disease burden, an effective vaccine or specific therapy are lacking which is largely due to our limited understanding of the immune response to rsv and how it relates to clinical disease severity. current treatment for rsv remains largely supportive and rsv-specific options for prophylaxis and/or treatment are limited to palivizumab an ...201525922289
respiratory syncytial virus in infants: is maternal vaccination a realistic strategy?respiratory syncytial virus (rsv) remains an important cause of serious and sometimes fatal acute lower respiratory tract disease in infants, yet no effective antiviral treatment or vaccine for the prevention of rsv in early life is available. vaccination of women during pregnancy is considered to be the most plausible strategy to provide direct rsv antibody protection to young infants during a period of greatest vulnerability.201525918956
association between respiratory infections in early life and later asthma is independent of virus type.lower respiratory tract infections in the first years of life are associated with later asthma, and this observation has led to a focus on the potential causal role of specific respiratory viruses, such as rhinoviruses and respiratory syncytial virus, in asthma development. however, many respiratory viruses and bacteria trigger similar respiratory symptoms and it is possible that the important risk factors for asthma are the underlying susceptibility to infection and the exaggerated reaction to ...201525910716
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