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role of hydrogen sulfide in paramyxovirus infections.hydrogen sulfide (h2s) is an endogenous gaseous mediator that has gained increasing recognition as an important player in modulating acute and chronic inflammatory diseases. however, its role in virus-induced lung inflammation is currently unknown. respiratory syncytial virus (rsv) is a major cause of upper and lower respiratory tract infections in children for which no vaccine or effective treatment is available. using the slow-releasing h2s donor gyy4137 and propargylglycin (pag), an inhibitor ...201525740991
serologic cross-reactions between nucleocapsid proteins of human respiratory syncytial virus and human metapneumovirus.human respiratory syncytial virus (hrsv) and human metapneumovirus (hmpv) share virologic and epidemiologic features and cause clinically similar respiratory illness predominantly in young children. in a previous study of acute febrile respiratory illness in bangladesh, we tested paired serum specimens from 852 children presenting fever and cough for diagnostic increases in titers of antibody to hrsv and hmpv by enzyme immunoassay (eia). unexpectedly, of 93 serum pairs that showed a ≥ 4-fold inc ...201525740767
recent vaccine development for human metapneumovirus.human metapneumovirus (hmpv) and respiratory syncytial virus, its close family member, are two major causes of lower respiratory tract infection in the paediatric population. hmpv is also a common cause of worldwide morbidity and mortality in immunocompromised patients and older adults. repeated infections occur often, demonstrating a heavy medical burden. however, there is currently no hmpv-specific prevention treatment. this review focuses on the current literature on hmpv vaccine development. ...201525667325
direct multiplexed whole genome sequencing of respiratory tract samples reveals full viral genomic information.acute respiratory tract infections (rti) cause substantial morbidity during childhood, and are responsible for the majority of pediatric infectious diseases. although most acute rti are thought to be of viral origin, viral etiology is still unknown in a significant number of cases.201525866327
clinical outcomes associated with respiratory virus detection before allogeneic hematopoietic stem cell transplant.the management of respiratory virus infections prior to hematopoietic cell transplant (hct) is difficult. we examined whether respiratory virus detection before hct influenced the requirement for bronchoscopy, hospitalization, and overall survival following hct.201525847977
viral etiology of acute lower respiratory tract infections in hospitalized young children in a children's referral hospital in iran.viruses are considered major causes of acute respiratory tract infections among children under 5 years old. in this study we investigated the prevalence of three respiratory viruses--respiratory syncytial virus (rsv), influenza virus (inf) and adenovirus (adv)--among hospitalized children with acute viral lower respiratory tract infections (lrtis). nasopharyngeal aspirates were collected from children under five who had been hospitalized for lrtis. the clinical data, including demographic data ( ...201525818953
comparison of bronchiolitis of human metapneumovirus and human respiratory syncytial virus. 201525790057
comparison of human metapneumovirus, respiratory syncytial virus and rhinovirus respiratory tract infections in young children admitted to hospital.respiratory syncytial virus (rsv), human metapneumovirus (hmpv), and rhinoviruses (rv) are frequent causes of respiratory tract infections in young children. we compared laboratory and clinical findings in children with comparable age distribution and hospitalized due to rsv, hmpv or rv infections. viral pathogens were detected by a quantitative real time pcr from nasopharyngeal aspirates. no significant differences in the admission diagnosis, laboratory parameters, patient demographics and trea ...201525074284
impact of a rapid respiratory panel test on patient outcomes.evolution of polymerase chain reaction testing for infectious pathogens has occurred concurrent with a focus on value-based medicine.201525152311
a broadly neutralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus.human metapneumovirus (hmpv) is a leading cause of acute respiratory tract infection, with significant morbidity and mortality. no licensed vaccines or therapeutic agents exist. monoclonal antibodies (mabs) are effective at preventing other infectious diseases and could be used against hmpv in high-risk hosts.201524864121
the pneumovirinae fusion (f) protein: a common target for vaccines and antivirals.the pneumovirinae fusion (f) protein mediates fusion of the virus and cell membrane, an essential step for entry of the viral genome in the cell cytoplasm and initiation of a new infectious cycle. accordingly, potent inhibitors of virus infectivity have been found among antibodies and chemical compounds that target the pneumovirinae f protein. recent developments in structure-based vaccines have led to a deeper understanding of f protein antigenicity, unveiling new conformations and epitopes whi ...201525738581
detection of respiratory tract pathogens with molecular biology methods.this paper describes the use in routine diagnosis of virological kit, which was designed to identify the 15 most common respiratory viruses in clinical specimens of nasopharyngeal aspirates, swabs, and bronchoalveolar lavage. it is a one-step multiplex rt-pcr system for the detection of influenza virus type a and type b, human respiratory syncytial virus type a, b; human adenovirus, human metapneumovirus, human coronaviruses 229e/nl63 and oc43, human parainfluenza type 1, 2, 3, human rhinovirus ...201525252894
hospital outbreak of human respiratory syncytial virus (hrsv) illness in immunocompromised hospitalized children during summer.the human respiratory syncytial virus (hrsv) is a community-acquired virus that mainly causes acute respiratory tract infection in infants and children. hrsv is increasingly recognized as an important nosocomial pathogen causing morbidity in immunocompromised patients. here, we are reporting a hospital outbreak of hrsv during summer in children receiving chemotherapy for haematological malignancies. prompt detection and timely preventive measures could abort the devastating outbreak.201524521518
blood mxa protein as a marker for respiratory virus infections in young children.type i interferon induced mxa response can differentiate viral from bacterial infections, but mxa responses in rhinovirus or asymptomatic virus infections are not known.201525542463
rapid and generic identification of influenza a and other respiratory viruses with mass spectrometry.the rapid identification of existing and emerging respiratory viruses is crucial in combating outbreaks and epidemics. matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) is a rapid and reliable identification method in bacterial diagnostics, but has not been used in virological diagnostics. mass spectrometry systems have been investigated for the identification of respiratory viruses. however, sample preparation methods were laborious and time-consuming. ...201525500183
occurrence of virus-induced copd exacerbations during four seasons.in this study, we investigated the occurrence of viral infections in acute exacerbations of chronic obstructive pulmonary disease (copd) during four seasons. viral infections were detected by the use of real-time reverse transcriptase polymerase chain reaction on pharyngeal swabs. during a 12-month period pharyngeal swabs were obtained in 136 exacerbations of 63 patients. in 35 exacerbations (25.7%) a viral infection was detected. most viral infections occurred in the winter (n = 14, 40.0%), fol ...201525426994
diagnosis of community-acquired acute respiratory illness: from conventional microbiological methods to molecular detection (multiplex).investigations of the etiologic agents of community-acquired acute respiratory illness may lead to better treatment decisions and patient outcomes. in a routine care setting, we assessed the diagnostic performance of a multiplex pcr assay with respect to conventional microbiological methods, in a continuous series of adult cases of community-acquired acute respiratory illness. we enrolled 279 adult patients hospitalised for community-acquired acute respiratory illness at tours university hospita ...201525596173
detection of common respiratory viruses in tonsillar tissue of children with obstructive sleep apnea.early life viral infection is associated with neurogenic inflammation that is present in lymphoid tissues of the upper airway in children with obstructive sleep apnea (osa). we hypothesized that viral genomic material is present in tonsils of children with osa. therefore, we examined tonsils for the presence of respiratory viruses' nucleic acids in children with osa, and in children without osa (undergoing surgery for recurrent throat infections (ri)).201524574078
community-acquired pneumonia requiring hospitalization among u.s. children.incidence estimates of hospitalizations for community-acquired pneumonia among children in the united states that are based on prospective data collection are limited. updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed.201525714161
effect of hypogammaglobulinemia on the incidence of community-acquired respiratory viral infections after lung transplantation.hypogammaglobulinemia (hgg) has been associated with an increased risk of infectious complications in lung transplant recipients, but its effect specifically on community-acquired respiratory viruses (carvs) remains unknown. this study aimed to determine if lung transplant recipients with hgg are at an increased risk of developing carv infection. secondary endpoints included the effect of hgg on lung function, incidence of rejection, and mortality.201523747186
single, dual and multiple respiratory virus infections and risk of hospitalization and mortality.respiratory virus infections cause a significant number of hospitalization and deaths globally. this study investigated the association between single and multiple respiratory virus infections and risk of admission to a general ward, intensive care unit or death in patients aged 0-105 years (mean ± s.d. = 24·4 ± 24·1 years), from north west england, that were tested for respiratory virus infections between january 2007 and june 2012. the majority of infections were in children aged ⩽5 years. dua ...201524568719
hospitalization incidence, mortality, and seasonality of common respiratory viruses over a period of 15 years in a developed subtropical city.information on respiratory viruses in subtropical region is limited.incidence, mortality, and seasonality of influenza (flu) a/b, respiratory syncytial virus (rsv), adenovirus (adv), and parainfluenza viruses (piv) 1/2/3 in hospitalized patients were assessed over a 15-year period (1998-2012) in hong kong.male predominance and laterally transversed j-shaped distribution in age-specific incidence was observed. incidence of flu a, rsv, and piv decreased sharply from infants to toddlers; whereas fl ...201526579810
heparin octasaccharide decoy liposomes inhibit replication of multiple viruses.heparan sulfate (hs) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (rsv), human parainfluenza virus 3 (hpiv3), and herpes simplex virus (hsv). decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as 'molecular sinks' and preventing the pathogen from binding to susceptible host cells. decoy receptors functionalized with hs could bi ...201525637710
enhanced neutralizing antibody response induced by respiratory syncytial virus prefusion f protein expressed by a vaccine candidate.respiratory syncytial virus (rsv) and human parainfluenza virus type 3 (hpiv3) are the first and second leading viral agents of severe respiratory tract disease in infants and young children worldwide. vaccines are not available, and an rsv vaccine is particularly needed. a live attenuated chimeric recombinant bovine/human piv3 (rb/hpiv3) vector expressing the rsv fusion (f) glycoprotein from an added gene has been under development as a bivalent vaccine against rsv and hpiv3. previous clinical ...201526157122
attenuated human parainfluenza virus type 1 (hpiv1) expressing the fusion glycoprotein of human respiratory syncytial virus (rsv) as a bivalent hpiv1/rsv vaccine.live attenuated recombinant human parainfluenza virus type 1 (rhpiv1) was investigated as a vector to express the respiratory syncytial virus (rsv) fusion (f) glycoprotein, to provide a bivalent vaccine against rsv and hpiv1. the rsv f gene was engineered to include hpiv1 transcription signals and inserted individually into three gene locations in each of the two attenuated rhpiv1 backbones. each backbone contained a single previously described attenuating mutation that was stabilized against de ...201526223633
sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against rsv in cotton rats.the respiratory syncytial virus (rsv) is responsible for as many as 199000 annual deaths worldwide. currently, there is no standard treatment for rsv disease and no vaccine. sendai virus (sev) is an attractive pediatric vaccine candidate because it elicits robust and long-lasting virus-specific b cell and t cell activities in systemic and mucosal tissues. the virus serves as a gene delivery system as well as a jennerian vaccine against its close cousin, human parainfluenza virus type 1. here we ...201525477211
regulation of viral rna synthesis by the v protein of parainfluenza virus 5.paramyxoviruses include many important animal and human pathogens. the genome of parainfluenza virus 5 (piv5), a prototypical paramyxovirus, encodes a v protein that inhibits viral rna synthesis. in this work, the mechanism of inhibition was investigated. using mutational analysis and a minigenome system, we identified regions in the n and c termini of the v protein that inhibit viral rna synthesis: one at the very n terminus of v and the second at the c terminus of v. furthermore, we determined ...201526378167
epidemiology and clinical outcome of lower respiratory tract infections by respiratory syncytial virus or parainfluenza virus type 3 in adults receiving treatment for either acute leukemia or severe aplastic anemia: a retrospective single center study. 201526204825
complete genome sequence of human respiratory syncytial virus from shanghai, china.we report here the complete genome sequence of human respiratory syncytial virus isolated from an outpatient child with fever and respiratory symptoms in shanghai, china, in 2014. phylogenetic analysis showed that the full-length respiratory syncytial virus (rsv) genome sequence belongs to human rsv (hrsv) group a.201526358591
gs-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein.gs-5806 is a small-molecule inhibitor of human respiratory syncytial virus fusion protein-mediated viral entry. during viral entry, the fusion protein undergoes major conformational changes, resulting in fusion of the viral envelope with the host cell membrane. this process is reproduced in vitro using a purified, truncated respiratory syncytial virus (rsv) fusion protein. gs-5806 blocked these conformational changes, suggesting a possible mechanism for antiviral activity.201526324264
acute and chronic airway disease after human respiratory syncytial virus infection in cotton rats (sigmodon hispidus).infection with respiratory syncytial virus (rsv) generally presents as a mild, upper airway disease in human patients but may cause severe lower airway disease in the very young and very old. progress toward understanding the mechanisms of rsv pathogenesis has been hampered by a lack of relevant rodent models. mice, the species most commonly used in rsv research, are resistant to upper respiratory infection and do not recapitulate the pattern of virus spread in the human host. to address the nee ...201526310461
the effect of dietary bovine colostrum on respiratory syncytial virus infection and immune responses following the infection in the mouse.human respiratory syncytial virus (hrsv) is the most common cause of respiratory tract infection among young children because of immature t cell immunity of them against hrsv. cd8 t cells play a pivotal role in clearing hrsv and preventing subsequent infection. we examined the effects of dietary bovine colostrum on virus infection and cd8 t cell responses following hrsv infection in the mouse model. mice received bovine colostrum for 14 days prior to hrsv challenge, and lung indexes (severity of ...201526310306
identification of ccl2, rarres2 and efnb2 as host cell factors that influence the multistep replication of respiratory syncytial virus.human respiratory syncytial virus (rsv) is a major causative agent of respiratory tract infections in children worldwide. preterm children or those with underlying cardiopulmonary disorders are at particularly high risk of developing severe and lethal rsv respiratory tract infections; however, there are currently no effective vaccines or anti-viral drugs. to identify targets for the development of drugs to treat rsv infections, we investigated host cell factors involved in the replication of rsv ...201526277777
human respiratory syncytial virus non-structural protein ns1 modifies mir-24 expression via transforming growth factor-β.human respiratory syncytial virus (rsv) is a major health challenge in the young and elderly owing to the lack of a safe and effective vaccine and proven antiviral drugs. understanding the mechanisms by which viral genes and proteins modulate the host response to infection is critical for identifying novel disease intervention strategies. in this study, the rsv non-structural protein ns1 was shown to suppress mir-24 expression during infection. lack of ns1 was linked to increased expression of m ...201526253191
expression of chicken interleukin-2 by a highly virulent strain of newcastle disease virus leads to decreased systemic viral load but does not significantly affect mortality in chickens.in mammals, interleukin 2 (il-2) has been shown to decrease replication or attenuate pathogenicity of numerous viral pathogens (herpes simplex virus, vaccinia virus, human respiratory syncytial virus, human immunodeficiency virus) by activating natural killer cells (nk), cytotoxic t lymphocytes and expanding subsets of memory cells. in chickens, il-2 has been shown to activate t cells, and as such it might have the potential to affect replication and pathogenesis of newcastle disease virus (ndv) ...201526253150
a druggable pocket at the nucleocapsid/phosphoprotein interaction site of human respiratory syncytial virus.presently, respiratory syncytial virus (rsv), the main cause of severe respiratory infections in infants, cannot be treated efficiently with antivirals. however, its rna-dependent polymerase complex offers potential targets for rsv-specific drugs. this includes the recognition of its template, the ribonucleoprotein complex (rnp), consisting of genomic rna encapsidated by the rsv nucleoprotein, n. this recognition proceeds via interaction between the phosphoprotein p, which is the main polymerase ...201526246564
conformational heterogeneity determined by folding and oligomer assembly routes of the interferon response inhibitor ns1 protein, unique to human respiratory syncytial virus.the nonstructural ns1 protein is an essential virulence factor of the human respiratory syncytial virus, with a predominant role in the inhibition of the host antiviral innate immune response. this inhibition is mediated by multiple protein-protein interactions and involves the formation of large oligomeric complexes. there is neither a structure nor sequence or functional homologues of this protein, which points to a distinctive mechanism for blocking the interferon response among viruses. the ...201526237467
potential treatment for the respiratory syncytial virus infections (hrsv). 201526191357
animal models of respiratory syncytial virus infection and disease.the study of human respiratory syncytial virus pathogenesis and immunity has been hampered by its exquisite host specificity, and the difficulties encountered in adapting this virus to a murine host. the reasons for this obstacle are not well understood, but appear to reflect, at least in part, the inability of the virus to block the interferon response in any but the human host. this review addresses some of the issues encountered in mouse models of respiratory syncytial virus infection, and de ...201526176495
intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice.pneumonia virus of mice (pvm) infection of balb/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. this model system was used to investigate delivery of the internal structural proteins of pvm as a potential vaccination strategy to protect against pneumovirus disease. ...201526529077
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
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
ficus religiosa l. bark extracts inhibit human rhinovirus and respiratory syncytial virus infection in vitro.ficus religiosa l. is one of the most relevant members of the family of moraceae. it is the most sacred tree of south asia, and it is used in traditional ayurvedic and unani medicine to cure respiratory disorders like cough, wheezing and asthma. some studies were performed to investigate the anti-asthmatic potential of f. religiosa bark, leaves and fruit extracts but none of them tested their antiviral activity against viruses responsible for the exacerbation of wheezing and asthma.201526528588
[human respiratory syncytial virus, genotype ontario]. 201526928507
rsv-specific airway resident memory cd8+ t cells and differential disease severity after experimental human infection.in animal models, resident memory cd8+ t (trm) cells assist in respiratory virus elimination but their importance in man has not been determined. here, using experimental human respiratory syncytial virus (rsv) infection, we investigate systemic and local virus-specific cd8+ t-cell responses in adult volunteers. having defined the immunodominance hierarchy, we analyse phenotype and function longitudinally in blood and by serial bronchoscopy. despite rapid clinical recovery, we note surprisingly ...201526687547
kinetics of respiratory syncytial virus (rsv) memphis strain 37 (m37) infection in the respiratory tract of newborn lambs as an rsv infection model for human infants.respiratory syncytial virus (rsv) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. the lamb lung has several key features conducive to modeling rsv infection in human infants, including susceptibility to human strains of rsv such as the a2, long, and memphis strain 37 (m37). in this study, the kinetics of m37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as ...201526641081
antiviral effect of emodin from rheum palmatum against coxsakievirus b5 and human respiratory syncytial virus in vitro.viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. the most common pathogens include coxsackie virus (cv) and respiratory syncytial virus (rsv). however, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. the present study aimed to examine the antiviral activities of emodin (an ingredient of rheum palmatum) against cvb5 and rsv infections, in an attempt to discover new antiv ...201526670446
vaccination with human papillomavirus pseudovirus-encapsidated plasmids targeted to skin using microneedles.human papilloma virus-like particles (hpv vlp) serve as the basis of the current licensed vaccines for hpv. we have previously shown that encapsidation of dna expressing the model antigen m/m2 from respiratory syncytial virus (rsv) in hpv pseudovirions (psv) is immunogenic when delivered intravaginally. because the hpv capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. in this study we asked: 1) whether hpv16 v ...201525785935
identification of a human respiratory syncytial virus cell entry inhibitor by using a novel lentiviral pseudotype system.lentiviral budding is governed by group-specific antigens (gag proteins) and proceeds in the absence of cognate viral envelope proteins, which has been exploited to create pseudotypes incorporating envelope proteins from nonlentiviral families. here, we report the generation of infectious lentiviral pseudoparticles incorporating human respiratory syncytial virus (hrsv) f protein alone (hrsv-fpp) or carrying sh, g, and f proteins (hrsv-sh/g/fpp). these particles recapitulate key infection steps o ...201526719246
molecular characterization of human respiratory syncytial virus subtype b: a novel genotype of subtype b circulating in china.human respiratory syncytial virus (hrsv) is major pathogen of lower respiratory tract infections in infants and young children worldwide. there have been many studies regarding hrsv subgroup a (hrsv-a) g protein genetic variability but little information about hrsv subtype b (hrsv-b) g protein genetic diversity and molecular evolution in china. thus, a survey of the molecular epidemiology and evolution of the g protein in china is of high importance. in this study, the circulation and genetic di ...201524910250
an investigation of the genetic basis of increased susceptibility to neutralization by anti-fusion glycoprotein antibody arising on passage of human respiratory syncytial virus in cell culture.human respiratory syncytial virus isolates have previously been shown to exhibit resistance to neutralization by anti-fusion glycoprotein antibodies that is lost on passage in cell culture. early passage resistant and late passage susceptible stocks of two virus isolates from different epidemics were cloned by plaque purification. early passage stocks of both isolates yielded predominantly neutralization resistant clones while late passage stocks yielded predominantly susceptible clones. on furt ...201524861209
control of pathogenic effector t-cell activities in situ by pd-l1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. we demonstrate here that the co-inhibitory molecule programmed cell death 1 (pd-1) is selectively upregulated on t cells within the respiratory tract during both murine and human rsv infection. importantly, the interaction of pd-1 with its ligand pd-l1 is vital to restrict the pro-inflammatory activities of lung effector t cells ...201525465101
dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease.human respiratory syncytial virus (rsv) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. previous studies in humans and animal models have shown that vaccination with formalin-inactivated rsv (fi-rsv) leads to prominent airway eosinophilic inflammation following rsv challenge; however, the roles of pulmonary eosinophilia in the antiviral response ...201525410867
benzimidazole analogs inhibit respiratory syncytial virus g protein function.human respiratory syncytial virus (hrsv) is a highly contagious paramyxovirus that infects most children by age two, generating an estimated 75,000-125,000 hospitalizations in the u.s. annually. hrsv is the most common cause of bronchiolitis and pneumonia among infants and children under 1year of age, with significant mortality among high-risk groups. a regulatory agency-approved vaccine is not available, and existing prophylaxis and therapies are limited to use in high-risk pediatric patients; ...201526116756
urokinase receptor-deficient mice mount an innate immune response to and clarify respiratory viruses as efficiently as wild-type mice.the plasminogen activator receptor (upar) is required for lung infiltration by innate immune cells in respiratory bacterial infections. in order to verify if this held true for respiratory viruses, wild type (wt) and upar knockout (upar(-/-)) mice were inoculated intranasally with the human respiratory syncytial virus (hrsv) and the influenza a virus. at several days post-infection (dpi), viral titers in the lungs were determined while cell infiltrates in the bronchoalveolar lavage (bal) were an ...201526115163
early evolution of human respiratory syncytial virus on1 strains: analysis of the diversity in the c-terminal hypervariable region of glycoprotein gene within the first 3.5 years since their detection.characterization of the phylogeny and diversity of human respiratory syncytial virus (hrsv) genotype on1 that occurred during its early evolution (within the first 3.5 years since the detection of the first on1 strains). on1 strains have a 72-nucleotide-long in-frame duplication within the second hypervariable domain of the glycoprotein gene (hvr2).201526112390
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
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
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
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
complete genome sequences of human respiratory syncytial virus genotype a and b isolates from south korea.there is a paucity of complete genome sequence information for human respiratory syncytial virus (hrsv). to this end, we sequenced the complete genome sequences of hrsv genotype a (hrsv-a/ic688/12) and genotype b (hrsv-b/gw0047/14 and hrsv-b/ic0027/14). this information will increase the understanding of hrsv genetic diversity, evolution, pathogenicity, antigenicity, and transmissibility.201525908140
monoclonal antibodies against the human respiratory syncytial virus obtained by immunization with epitope peptides and cpg-dna-liposome complex.respiratory syncytial virus (rsv) is the major cause of pulmonary inflammation in infants, young children, and immunocompromised adults. however, the rsv vaccine is not yet available commercially. the rsv-f glycoprotein mediates virus-host cell fusion, leading to syncytial formation; therefore, the rsv-f glycoprotein has been a treatment target for prevention and therapy of rsv infection. to produce the rsv-f-protein epitope-specific monoclonal antibody (mab), balb/c mice were immunized with a c ...201525897608
revealing the binding mode between respiratory syncytial virus fusion protein and benzimidazole-based inhibitors.human respiratory syncytial virus (hrsv) is a major respiratory pathogen in newborn infants and young children and can also be a threat to some elderly and high-risk adults with chronic pulmonary disease and the severely immunocompromised. the rsv fusion (rsvf) protein has been an attractive target for vaccine and drug development. experimental results indicate a series of benzimidazole-based inhibitors which target rsvf protein to inhibit the viral entry of rsv. to reveal the binding mode betwe ...201525872614
local evolutionary patterns of human respiratory syncytial virus derived from whole-genome sequencing.human respiratory syncytial virus (rsv) is associated with severe childhood respiratory infections. a clear description of local rsv molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. we have generated 27 complete or nearly complete genomes of rsv from hospitalized children attending a rural coastal district hospital in kilifi, kenya, over a 10-year period using a novel full-genome deep-sequ ...201525609811
discovery of an oral respiratory syncytial virus (rsv) fusion inhibitor (gs-5806) and clinical proof of concept in a human rsv challenge study.gs-5806 is a novel, orally bioavailable rsv fusion inhibitor discovered following a lead optimization campaign on a screening hit. the oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. a mean ec50 = 0.43 nm was found toward a panel of 75 rsv a and b clinical isolates and dose-dependent antiviral efficacy in the co ...201525574686
recombinant subgroup b human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats.human respiratory syncytial virus (hrsv) is the most important viral cause of severe respiratory tract disease in infants. two subgroups (a and b) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. existing in vitro and in vivo models of hrsv focus almost exclusively on subgroup a viruses. here, a recombinant (r) subgroup b virus (rhrsv(b05)) was generated based on a consensus genome sequence obtained directly from an unpas ...201525540371
evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques.there is no large-scale therapy available against human respiratory syncytial virus (hrsv), a major pathogen responsible for acute respiratory diseases. macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. however, the parameters that influence hrsv growth and control in this model are still poorly understood. we have documented in the following study the influence of age as well as repeated ...201525537374
proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.the aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (hrsv), a major cause of paediatric illness.201525533920
sedimentation equilibrium of a small oligomer-forming membrane protein: effect of histidine protonation on pentameric stability.analytical ultracentrifugation (auc) can be used to study reversible interactions between macromolecules over a wide range of interaction strengths and under physiological conditions. this makes auc a method of choice to quantitatively assess stoichiometry and thermodynamics of homo- and hetero-association that are transient and reversible in biochemical processes. in the modality of sedimentation equilibrium (se), a balance between diffusion and sedimentation provides a profile as a function of ...201525867485
molecular epidemiology and molecular characterization of respiratory syncytial viruses at a tertiary care university hospital in catalonia (spain) during the 2013-2014 season.human respiratory syncytial virus (hrsv) is the main cause of lower respiratory tract infections among infants and young children.201525866332
development of two salmonella-based oral vaccines against human respiratory syncytial virus.human respiratory syncytial virus is the most common cause of bronchiolitis and other respiratory infections in infants and the elderly worldwide. we have developed two new oral vaccines using salmonella typhi ty21a to carry and express the immunogenic epitopes of rsv fusion (f) and attachment (g) glycoproteins on its surface, separately. to evaluate the efficacy of the designed vaccines, balb/c mice were orally immunized and then infected with rsv. immune response analyses showed that cellmedia ...201525864737
interaction between human bap31 and respiratory syncytial virus small hydrophobic (sh) protein.the small hydrophobic (sh) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hrsv). deletion of sh protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. we have used a membrane-based yeast two-hybrid system (mby2h) and a library from human lung cdna to detect proteins that bind sh protein. this led to the identification of a membrane protein, b-cell associated protein 31 (bap31). transfected sh protein ...201525854864
respiratory syncytial virus infection in older adults: an under-recognized problem.human respiratory syncytial virus (rsv) is an enveloped, single-stranded, negative-sense rna virus and member of the paramyxoviridae family of the genus pneumovirus that was first reported as a major pathogen in pediatric populations. however, since its discovery, rsv has not infrequently been detected in adults. reinfection occurs throughout life, with more severe disease occurring in older adults, immunocompromised patients, and those with underlying cardiopulmonary disease. initially describe ...201525851217
small hydrophobic protein of respiratory syncytial virus as a novel vaccine antigen. 201525804473
sequencing and analysis of globally obtained human respiratory syncytial virus a and b genomes.human respiratory syncytial virus (rsv) is the leading cause of respiratory tract infections in children globally, with nearly all children experiencing at least one infection by the age of two. partial sequencing of the attachment glycoprotein gene is conducted routinely for genotyping, but relatively few whole genome sequences are available for rsv. the goal of our study was to sequence the genomes of rsv strains collected from multiple countries to further understand the global diversity of r ...201525793751
genetic variability in g2 and f2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure.human respiratory syncytial virus (hrsv) is an important respiratory pathogens among children between zero-five years old. host immunity and viral genetic variability are important factors that can make vaccine production difficult. in this work, differences between biological clones of hrsv were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. viral clones were selected by plaque ...201525650769
scop3d: three-dimensional visualization of sequence conservation.the integration of a protein's structure with its known sequence variation provides insight on how that protein evolves, for instance in terms of (changing) function or immunogenicity. yet, collating the corresponding sequence variants into a multiple sequence alignment, calculating each position's conservation, and mapping this information back onto a relevant structure is not straightforward. we therefore built the sequence conservation on protein 3d structure (scop3d) tool to perform these ta ...201525641949
the viral transcription group determines the hla class i cellular immune response against human respiratory syncytial virus.the cytotoxic t-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class i molecules that are exposed on the surface of infected cells. the cytotoxic t-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. in this study, naturally processed viral human leukocyte antigen class i ligands were identified with mass spectrometry analysis of complex human leukoc ...201525635267
molecular characterization of human respiratory syncytial virus in the philippines, 2012-2013.human respiratory syncytial virus (hrsv) is a major cause of acute lower respiratory tract infections in infants and children worldwide. we performed molecular analysis of hrsv among infants and children with clinical diagnosis of severe pneumonia in four study sites in the philippines, including biliran, leyte, palawan, and metro manila from june 2012 to july 2013. nasopharyngeal swabs were collected and screened for hrsv using real-time polymerase chain reaction (pcr). positive samples were te ...201526540236
genetic diversity and evolutionary insights of respiratory syncytial virus a on1 genotype: global and local transmission dynamics.human respiratory syncytial virus (rsv) a on1 genotype, first detected in 2010 in ontario, canada, has been documented in 21 countries to date. this study investigated persistence and transmission dynamics of on1 by grouping 406 randomly selected rsv-positive specimens submitted to public health ontario from august 2011 to august 2012; rsv-a-positive specimens were genotyped. we identified 370 rsv-a (181 na1, 135 na2, 51 on1 3 ga5) and 36 rsv-b positive specimens. we aligned time-stamped second ...201526420660
direct whole-genome deep-sequencing of human respiratory syncytial virus a and b from vietnamese children identifies distinct patterns of inter- and intra-host evolution.human respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infections in children ,2 years of age. little is known about rsv intra-host genetic diversity over the course of infection or about the immune pressures that drive rsv molecular evolution. we performed whole-genome deep-sequencing on 53 rsv-positive samples (37 rsv subgroup a and 16 rsv subgroup b) collected from the upper airways of hospitalized children in southern vietnam over two consecutive seasons. rsv a ...201526407694
molecular evolution of the hypervariable region of the attachment glycoprotein gene in human respiratory syncytial virus subgroup b genotypes ba9 and ba10.we studied the molecular evolution of the c-terminal 3rd hypervariable region in the attachment glycoprotein gene of human respiratory syncytial virus subgroup b (hrsv-b) genotypes ba9 and ba10. we performed time-scaled phylogenetic analyses using bayesian markov chain monte carlo methods. we also performed a genetic distance analysis (p-distance analysis), positive and negative selection analyses, and a bayesian skyline plot (bsp) analysis. we found that genotype ba9 diverged from the common an ...201526408340
retrospective phylogenetic analysis of circulating ba genotype of human respiratory syncytial virus with 60 bp duplication from new delhi, india during 2007-2010.human respiratory syncytial virus (hrsv) is the most common viral pathogen of acute lower respiratory tract infection in infants and young children. the g protein of hrsv is the trans-membrane glycoprotein that is involved in the attachment of virion with the host cell. the nasopharyngeal aspirates were subjected to rt-pcr for the second hypervariable region of the g protein gene in the present investigation. sequencing and phylogenetic analysis revealed that all the study strains clustered with ...201526645038
tangeretin from citrus reticulate inhibits respiratory syncytial virus replication and associated inflammation in vivo.human respiratory syncytial virus (rsv) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. our previous study showed that tangeretin from citrus reticulate possessed potent in vitro anti-rsv effects comparable to that of ribavirin. therefore, in this study, we investigated the in vivo anti-rsv activity of tangeretin in 3-week-old male balb/c mice. a plaque reduction assay and fluorescence quantitative polymerase chain reaction (fq-pcr) showed that tangere ...201526468759
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
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
the interferon type i/iii response to respiratory syncytial virus infection in airway epithelial cells can be attenuated or amplified by antiviral treatment.human respiratory syncytial virus (rsv) is a single-stranded rna virus that causes acute, and occasionally fatal, lower respiratory illness in young infants, the elderly, and immunocompromised patients. therapeutic interventions able to cut short viral replication and quickly return the airways to normal function are needed. an understanding of antiviral activities and their effects on host defense mechanisms is important for the design of safe and effective therapy. we targeted functionally and ...201526608311
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
human respiratory syncytial virus and th1 chemokines.the importance of the type-1 helper (th1) chemokines in rsv (respiratory syncytial virus) infection has been shown by several studies, in animal models, and in humans. the production of th1 chemokines within the lower respiratory tract has been shown in patients with rsv bronchiolitis, particularly chemokine (c-x-c motif) ligand (cxcl)10/interferon-γ-inducible protein 10 (ip-10), whose plasma levels were markedly elevated in acute infection. rsv fusion (f) or large (g) protein treatment of fully ...201526152633
respiratory syncytial virus attachment glycoprotein contribution to infection depends on the specific fusion protein.human respiratory syncytial virus (rsv) is an important pathogen causing acute lower respiratory tract disease in children. the rsv attachment glycoprotein (g) is not required for infection, as g-null rsv replicates efficiently in several cell lines. our laboratory previously reported that the viral fusion (f) protein is a determinant of strain-dependent pathogenesis. here, we hypothesized that virus dependence on g is determined by the strain specificity of f. we generated recombinant viruses e ...201526468535
novel therapies and vaccines against the human respiratory syncytial virus.human respiratory syncytial virus (hrsv) is the leading cause of acute lower respiratory tract infections worldwide in infants, as well as an important pathogen affecting the elderly and immunocompromised individuals. despite more than a half a century of research, no licensed vaccines are available and only palivizumab has been approved to use in humans, mostly recommended or limited to high risk infants. therefore, novel therapeutic and preventive drugs need to be developed to fight this major ...201526457559
respiratory syncytial virus induces indoleamine 2,3-dioxygenase activity: a potential novel role in the development of allergic disease.infants that develop severe bronchiolitis due to respiratory syncytial virus (rsv) are at increased risk of developing asthma later in life. we investigated a potential immunological mechanism for the association between rsv and the development of allergic inflammation. the enzyme indoleamine 2,3-dioxygenase (ido) has been reported to induce selective apoptosis of t helper 1 (th1) cells and contributed to th2-biased immune responses.201525627660
genetic variability in g2 and f2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure.human respiratory syncytial virus (hrsv) is an important respiratory pathogens among children between zero-five years old. host immunity and viral genetic variability are important factors that can make vaccine production difficult. in this work, differences between biological clones of hrsv were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. viral clones were selected by plaque ...201525742274
coinfection with blood-stage plasmodium promotes systemic type i interferon production during pneumovirus infection but impairs inflammation and viral control in the lung.acute lower respiratory tract infections (alrti) are the leading cause of global childhood mortality, with human respiratory syncytial virus (hrsv) being a major cause of viral alrti in young children worldwide. in sub-saharan africa, many young children experience severe illnesses due to hrsv or plasmodium infection. although the incidence of malaria in this region has decreased in recent years, there remains a significant opportunity for coinfection. recent data show that febrile young childre ...201525716232
characterization of hospital and community-acquired respiratory syncytial virus in children with severe lower respiratory tract infections in ho chi minh city, vietnam, 2010.human respiratory syncytial virus (rsv) is an important community and nosocomial pathogen in developed countries but data regarding the importance of rsv in developing countries are relatively scarce.201525702707
dimerization of matrix protein is required for budding of respiratory syncytial virus.respiratory syncytial virus (rsv) infects epithelial cells of the respiratory tract and is a major cause of bronchiolitis and pneumonia in children and the elderly. the virus assembles and buds through the plasma membrane, forming elongated membrane filaments, but details of how this happens remain obscure. oligomerization of the matrix protein (m) is a key step in the process of assembly and infectious virus production. in addition, it was suggested to affect the conformation of the fusion prot ...201525673702
discovery of 4'-chloromethyl-2'-deoxy-3',5'-di-o-isobutyryl-2'-fluorocytidine (als-8176), a first-in-class rsv polymerase inhibitor for treatment of human respiratory syncytial virus infection.respiratory syncytial virus (rsv) is a leading pathogen of childhood and is associated with significant morbidity and mortality. to date, ribavirin is the only approved small molecule drug, which has limited use. the only other rsv drug is palivizumab, a monoclonal antibody, which is used for rsv prophylaxis. clearly, there is an urgent need for small molecule rsv drugs. this article reports the design, synthesis, anti-rsv activity, metabolism, and pharmacokinetics of a series of 4'-substituted ...201525667954
an attraction-repulsion point process model for respiratory syncytial virus infections.how is the progression of a virus influenced by properties intrinsic to individual cells? we address this question by studying the susceptibility of cells infected with two strains of the human respiratory syncytial virus (rsv-a and rsv-b) in an in vitro experiment. spatial patterns of infected cells give us insight into how local conditions influence susceptibility to the virus. we observe a complicated attraction and repulsion behavior, a tendency for infected cells to lump together or remain ...201525660222
identification and characterization of the binding site of the respiratory syncytial virus phosphoprotein to rna-free nucleoprotein.the rna genome of respiratory syncytial virus (rsv) is constitutively encapsidated by the viral nucleoprotein n, thus forming a helical nucleocapsid. polymerization of n along the genomic and antigenomic rnas is concomitant to replication and requires the preservation of an unassembled monomeric nucleoprotein pool. to this end, and by analogy with paramyxoviridae and rhabdoviridae, it is expected that the viral phosphoprotein p acts as a chaperone protein, forming a soluble complex with the rna- ...201525568210
new host factors important for respiratory syncytial virus (rsv) replication revealed by a novel microfluidics screen for interactors of matrix (m) protein.although human respiratory syncytial virus (rsv) is the most common cause of bronchiolitis and pneumonia in infants and elderly worldwide, there is no licensed rsv vaccine or effective drug treatment available. the rsv matrix protein plays key roles in virus life cycle, being found in the nucleus early in infection in a transcriptional inhibitory role, and later localizing in viral inclusion bodies before coordinating viral assembly and budding at the plasma membrane. in this study, we used a no ...201525556234
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