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[prophylaxis against respiratory viral disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation].respiratory viruses have been identified as a cause of morbidity and mortality in patients undergoing sot and hsct, specially in children. the most frequent are respiratory syncytial virus (rsv), influenza (flu), parainfluenza (pi) and adenovirus (adv). these infections are associated with progression to severe lower respiratory tract infections in up to 60% of the cases. it is advised to apply universal protection recommendations for respiratory viruses (a2) and some specific measures for flu a ...201223282554
non-benzimidazole containing inhibitors of respiratory syncytial virus.several non-benzimidazole containing inhibitors of respiratory syncytial virus are described. core template modification, analysis of antiviral activity, physicochemistry and optimisation of properties led to the thiazole-imidazole 13, that showed a good potency and pharmacokinetic profile in the rat.201223265891
epidemiology of respiratory viral infections in two long-term refugee camps in kenya, 2007-2010.abstract: background: refugees are at risk for poor outcomes from acute respiratory infections (ari) because of overcrowding, suboptimal living conditions, and malnutrition. we implemented surveillance for respiratory viruses in dadaab and kakuma refugee camps in kenya to characterize their role in the epidemiology of ari among refugees. methods: from 1 september 2007 through 31 august 2010, we obtained nasopharyngeal (np) and oropharyngeal (op) specimens from patients with influenza-like illne ...201222251705
[rhinoviruses. frequency in nonhospitalized children with acute respiratory infection].molecular methods for human rhinoviruses (hrv) have increased the sensitivity in their diagnosis. hrv may cause acute respiratory infections (ari) of the upper and lower respiratory tract. hrv infection during childhood is a predictor of asthma development. in this study, the hrv frequency in outpatient children with ari was determined, and their clinical features and previous conditions were evaluated. a total of 186 respiratory samples of children under 6 year old attending the cemic pediatric ...201222257453
regulatory t cells expressing granzyme b play a critical role in controlling lung inflammation during acute viral infection.the inflammatory response to lung infections must be tightly regulated, enabling pathogen elimination while maintaining crucial gas exchange. using recently described "depletion of regulatory t cell" (dereg) mice, we found that selective depletion of regulatory t cells (tregs) during acute respiratory syncytial virus (rsv) infection enhanced viral clearance but increased weight loss, local cytokine and chemokine release, and t-cell activation and cellular influx into the lungs. conversely, infla ...201222236998
molecular evolution of respiratory syncytial virus fusion gene, canada, 2006-2010.to assess molecular evolution of the respiratory syncytial virus (rsv) fusion gene, we analyzed rsv-positive specimens from 123 children in canada who did or did not receive rsv immunoprophylaxis (palivizumab) during 2006-2010. resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.201222264682
respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis.objectives: we investigated factors associated with morbidity and pediatric intensive care unit (picu) admission in children with respiratory syncytial virus (rsv) infection and explored seasonality and implication of prophylaxis. methods: a retrospective study between 2006 and 2008 of every child with a laboratory-confirmed rsv infection was included. results: six hundred seventy rsv admissions were identified. ten (1.5%) required picu admissions. children admitted to picu were younger than non ...201222227087
proteins involved in extracellular matrix dynamics are associated with rsv disease severity.severity of respiratory syncytial virus (rsv) infection ranges widely. to what extent the local immune response is involved in rsv disease pathogenesis and which markers of this response are critical in determining disease severity is still matter of debate.the local immune response was studied in nasopharyngeal aspirates (npas) during rsv infection. forty-seven potential markers of disease severity were analysed in a screening cohort of rsv-infected infants with mild disease at home (n=8), hosp ...201222267765
role of neutralizing antibodies in adults with community-acquired pneumonia by respiratory syncytial virus.background. respiratory syncytial virus (rsv) has been implicated in the etiology of adult community-acquired pneumonia (cap). we investigated rsv infection in chilean adults with cap using direct viral detection, real-time reverse-transcription polymerase chain reaction (rtrt-pcr), and serology (microneutralization assay).methods. rsv, other respiratory viruses, and bacteria were studied by conventional and molecular techniques in adults aged ≥18 years presenting with cap to the healthcare faci ...201222238168
Making sense of cell surface nucleolin: Implications for respiratory syncytial virus prophylaxis and therapy.Comment on: Tayyari F, et al. Nat Med 2011; 17:1132-5.201222185777
independent structural domains in the paramyxovirus polymerase protein.all enzymatic activities required for genomic replication and transcription of nonsegmented negative strand rna viruses (nnsv or mononegavirales) are believed to be concentrated in the viral polymerase (l) protein. however, our insight into the organization of these different enzymatic activities into a bioactive tertiary structure remains rudimentary. fragments of mononegavirales polymerases analyzed to date cannot restore bioactivity through trans-complementation, unlike the related l proteins ...201222215662
vesicular stomatitis virus as an oncolytic agent against pancreatic ductal adenocarcinoma.vesicular stomatitis virus (vsv) is a promising oncolytic agent against a variety of cancers. however, it has never been tested in any pancreatic cancer model. pancreatic ductal adenocarcinoma (pda) is the most common and aggressive form of pancreatic cancer. in this study, the oncolytic potential of several vsv variants was analyzed in a panel of 13 clinically relevant human pda cell lines and compared to conditionally replicative adenoviruses (crads), sendai virus and respiratory syncytial vir ...201222238308
when are amniotic fluid viral pcr studies indicated in prenatal diagnosis?objective: to determine which prenatal ultrasound findings indicate the need to also obtain pcr studies for viral genome in women undergoing midtrimester amniocentesis. methods: this was a retrospective observational study on women that underwent amniotic fluid karyotyping and viral pcr testing for history or ultrasound based indication. amniotic fluid was tested for adenovirus, cytomegalovirus, respiratory syncytial virus, enterovirus, epstein-barr virus, and parvovirus b19 using multiplex pcr ...201222275111
il-21 promotes the pathologic immune response to pneumovirus infection.il-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of b cells, increased ig production, and the development of th17 and t follicular helper cells. il-21 is also implicated in the development of autoimmune disease and has antitumor activity. in this study, we investigated the role of il-21 in host defense to pneumonia virus of mice (pvm), which initiates an infection in mice resembling that of respiratory syncytial virus disease in humans. we found that pvm-infected ...201222238461
respiratory syncytial virus regulates human micrornas by using mechanisms involving beta interferon and nf-κb.respiratory syncytial virus (rsv) is the most common viral cause of severe lower respiratory tract illness in infants and children. the virus replicates in polarized epithelial cells in the airway and, to a lesser extent, infects airway antigen-presenting cells, such as dendritic cells (dcs). rsv possesses a number of expressed genes that antagonize the effect of type i interferons and other related host factor pathways that inhibit replication efficiency. virus infection alters host gene transc ...201223249809
burden of respiratory syncytial virus infection in young children.respiratory syncytial virus (rsv) is the most frequent and important cause of lower respiratory tract infection in infants and children. it is a seasonal virus, with peak rates of infection occurring annually in the cold season in temperate climates, and in the rainy season, as temperatures fall, in tropical climates. high risk groups for severe rsv disease include infants below six mo of age, premature infants with or without chronic lung disease, infants with hemodynamically significant congen ...201225254161
vigor extended to annotate genomes for additional 12 different viruses.a gene prediction program, vigor (viral genome orf reader), was developed at j. craig venter institute in 2010 and has been successfully performing gene calling in coronavirus, influenza, rhinovirus and rotavirus for projects at the genome sequencing center for infectious diseases. vigor uses sequence similarity search against custom protein databases to identify protein coding regions, start and stop codons and other gene features. ribonucleicacid editing and other features are accurately ident ...201222669909
comparing the use of, and considering the need for, lumbar puncture in children with influenza or other respiratory virus infections.the clinical presentation of influenza in infancy may be similar to serious bacterial infection and be investigated with invasive procedures like lumbar puncture (lp), despite very limited evidence that influenza occurs concomitantly with bacterial meningitis, perhaps because the diagnosis of influenza is very often not established when the decision to perform lp is being considered.201223122417
evaluation of a multiplex real-time pcr assay for the detection of respiratory viruses in clinical specimens.in this study, we evaluated the analytical performance and clinical potential of a one-step multiplex real-time pcr assay for the simultaneous detection of 14 types of respiratory viruses using the advansure rv real-time pcr kit (lg life sciences, korea).201223130338
respiratory syncytial virus infection: mechanisms of redox control and novel therapeutic opportunities.respiratory syncytial virus (rsv) is one of the most important causes of upper and lower respiratory tract infections in infants and young children, for which no effective treatment is currently available. although the mechanisms of rsv-induced airway disease remain incompletely defined, the lung inflammatory response is thought to play a central pathogenetic role. in the past few years, we and others have provided increasing evidence of a role of reactive oxygen species (ros) as important regul ...201222799599
replication of respiratory syncytial virus is inhibited by the host defense molecule viperin.respiratory syncytial virus (rsv) is an important viral pathogen of otitis media, bronchiolitis, and pneumonia. as infection of the upper airways is a precondition for the development of these diseases, understanding rsv pathogenesis and the host response induced by rsv in this niche may enable the development of novel therapeutic strategies against this virus. we have used a microarray approach and showed that expression of the gene that encodes the antiviral protein viperin was significantly u ...201223018837
the small hydrophobic protein of the human respiratory syncytial virus forms pentameric ion channels.the small hydrophobic (sh) protein is encoded by the human respiratory syncytial virus. its absence leads to viral attenuation in the context of whole organisms, and it prevents apoptosis in infected cells. herein, we have examined the structure of sh protein in detergent micelles and in lipid bilayers, by solution nmr and attenuated total reflection-fourier transform infrared spectroscopy, respectively. we found that sh protein has a single α-helical transmembrane domain and forms homopentamers ...201222621926
innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial virus bronchiolitis.most patients with respiratory syncytial virus (rsv) bronchiolitis requiring admission to the pediatric intensive care unit (picu) have no risk factors for severe disease. we sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and rsv disease severity.201223204162
comparison of the etiology of viral respiratory illnesses in inner-city and suburban infants.the risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct.201223014674
response to infections in patients with asthma and atopic disease: an epiphenomenon or reflection of host susceptibility?associations between respiratory tract infections and asthma inception and exacerbations are well established. infant respiratory syncytial virus and rhinovirus infections are known to be associated with an increased risk of asthma development, and among children with prevalent asthma, 85% of asthma exacerbations are associated with viral infections. however, the exact nature of this relationship remains unclear. is the increase in severity of infections an epiphenomenon, meaning respiratory tra ...201222846746
respiratory syncytial virus promotes moraxella catarrhalis-induced ascending experimental otitis media.otitis media (om) is a polymicrobial disease wherein prior or concurrent infection with an upper respiratory tract virus plays an essential role, predisposing the middle ear to bacterial invasion. in episodes of acute bacterial om, respiratory syncytial virus (rsv) is the most commonly isolated virus and thus serves as an important co-pathogen. of the predominant bacterial agents of om, the pathogenesis of disease due to moraxella catarrhalis is the least well understood. rigorous study of m. ca ...201222768228
il1rl1 gene variants and nasopharyngeal il1rl-a levels are associated with severe rsv bronchiolitis: a multicenter cohort study.targets for intervention are required for respiratory syncytial virus (rsv) bronchiolitis, a common disease during infancy for which no effective treatment exists. clinical and genetic studies indicate that il1rl1 plays an important role in the development and exacerbations of asthma. human il1rl1 encodes three isoforms, including soluble il1rl1-a, that can influence il33 signalling by modifying inflammatory responses to epithelial damage. we hypothesized that il1rl1 gene variants and soluble il ...201222574108
effect of chemokine receptor cx3cr1 deficiency in a murine model of respiratory syncytial virus infection.respiratory syncytial virus (rsv) is the most common cause of serious lower respiratory illness in infants and young children worldwide, making it a high priority for development of strategies for prevention and treatment. rsv can cause repeat infections throughout life, with serious complications in elderly and immunocompromised patients. previous studies indicate that the rsv g protein binds through a cx3c chemokine motif to the host chemokine receptor, cx3cr1, and modulates the inflammatory i ...201222330646
comparison of the luminex xtag rvp fast assay and the idaho technology filmarray rp assay for detection of respiratory viruses in pediatric patients at a cancer hospital.respiratory viruses are increasingly recognized as serious causes of morbidity and mortality in immunocompromised patients. the rapid and sensitive detection of respiratory viruses is essential for the early diagnosis and administration of appropriate antiviral therapy, as well as for the effective implementation of infection control measures. we compared the performance of two commercial assays, xtag rvp fast (luminex diagnostics, toronto, canada) and filmarray rvp (fa rvp; idaho technology, sa ...201222518855
il-10 regulates viral lung immunopathology during acute respiratory syncytial virus infection in mice.interleukin (il-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. here we demonstrate that infection of balb/c mice with respiratory syncytial virus (rsv) induced il-10 production by cd4(+) and cd8(+) t cells in the airways at later time points (e.g. day 8); a proportion of these cells also co-produced ifn-γ. furthermore, rsv infection of il-10(-/-) mice resulted in more severe disease with enhanced weight loss, d ...201222393401
potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate.a number of different viruses including respiratory syncytial virus (rsv) initiate infection of cells by binding to cell surface glycosaminoglycans and sulfated oligo- and polysaccharide mimetics of these receptors exhibit potent antiviral activity in cultured cells. we investigated whether the introduction of different lipophilic groups to the reducing end of sulfated oligosaccharides would modulate their anti-rsv activity. our results demonstrate that the cholestanol-conjugated tetrasaccharide ...201222101246
Human bocavirus and other respiratory viral infections in a 2-year cohort of hospitalized children.Human bocavirus (HBoV) infection is reported worldwide and may cause severe respiratory tract infections. The aim of the present study was to assess the prevalence of HBoV, and other respiratory viral pathogens, in a 2-year retrospective study of children admitted to hospital, and to investigate whether viral loads of HBoV DNA were associated with severity of infection. Between April 2007 and March 2009, 891 respiratory samples from 760 children admitted to hospital with acute respiratory tract ...201222028039
seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay.abstract background: nucleic acid amplification tests are increasingly being used to diagnose viral and bacterial respiratory tract infections. the high sensitivity of these tests affects our understanding of the epidemiology of respiratory tract infections. we have assessed the detection rate of a multiplex real-time polymerase chain reaction (pcr) test, with emphasis on epidemiology and seasonal distribution of the most common respiratory tract infections. methods: seven thousand eight hundr ...201221867470
effect of respiratory syncytial virus infection on plasmacytoid dendritic cell regulation of allergic airway inflammation.respiratory syncytial virus (rsv) can infect myeloid dendritic cells (mdcs) and regulate their function in the development of allergy. it has been widely reported that plasmacytoid dcs (pdcs) play a critical role in antiviral innate immunity. in contrast, not much is known about the role of pdcs in the interaction between allergy and viral infection. the purpose of the present study was to investigate the effect of rsv infection on pdc function in the regulation of allergic airway inflammation i ...201221894025
Cholesterol-rich lipid rafts are required for release of infectious human respiratory syncytial virus particles.Cholesterol and sphingolipid enriched lipid raft micro-domains in the plasma membrane play an important role in the life-cycle of numerous enveloped viruses. Although human respiratory syncytial virus (RSV) proteins associate with the raft domains of infected cells and rafts are incorporated in RSV virion particles, the functional role of raft during RSV infection was unknown. In the current study we have identified rafts as an essential component of host cell that is required for RSV infection. ...201222088217
respiratory syncytial virus (rsv) community-acquired pneumonia (cap) in a hospitalized adult with human immunodeficiency virus (hiv) mimicking influenza a and pneumocystis (carinii) jiroveci pneumonia (pcp).respiratory syncytial virus (rsv) is an important cause of lower respiratory tract infections in young children, the elderly, and immunocompromised hosts, but rsv is a rare cause of community-acquired pneumonia (cap) in hospitalized adults with human immunodeficiency virus (hiv). in patients with hiv, cap is most frequently attributable to the usual bacterial respiratory pathogens that cause cap in immunocompetent hosts, eg, streptococcuspneumoniae or hemophilus influenzae. adults with hiv are a ...201222005289
l-carbocisteine inhibits respiratory syncytial virus infection in human tracheal epithelial cells.to examine the effects of l-carbocisteine on airway infection with respiratory syncytial (rs) virus, human tracheal epithelial cells were pretreated with l-carbocisteine and infected with rs virus. viral titer, virus rna, and pro-inflammatory cytokine secretion, including interleukin (il)-1 and il-6, increased with time after infection. l-carbocisteine reduced the viral titer in the supernatant fluids, the amount of rs virus rna, rs virus infection susceptibility, and the concentration of pro-in ...201222080978
isolation of influenza viruses in mdck 33016pf cells and clearance of contaminating respiratory viruses.this paper summarizes results obtained by multiplex pcr screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in mdck 33016pf cells. using the resplexii v2.0 (qiagen) multiplex pcr, 393 positive results were obtained in 468 clinical samples collected during an influenza season in germany. the overall distribution of positive results was influenza a 42.0%, influenza b 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronaviru ...201222119922
Ge-Gen-Tang has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines.Ge-Gen-Tang (GGT) has been used against adult respiratory tract infection for thousand years in ancient China. However, GGT is unable to inhibit influenza virus. The effect of GGT to manage respiratory tract viral infection has been questioned. Several ingredients of GGT and their constituents are able to inhibit various viruses. Therefore, GGT might have antiviral activity against other viruses causing respiratory tract illness. Human respiratory syncytial virus (HRSV) is one of the most import ...201222120014
Primary airway epithelial cultures from children are highly permissive to respiratory syncytial virus infection.Background Respiratory syncytial virus (RSV) infection of airway epithelial cells (AECs) is an important initial event in RSV bronchiolitis. AEC immunological responses are thought to be critical in driving the subsequent inflammation in the airway. This study examined viral replication, cytotoxicity and cytokine production in cultures of primary AECs from children compared with responses to RSV infection in an immortalised epithelial cell line and to those from infants with RSV bronchiolitis. ...201221865207
Clinical evaluation of multiplex real-time PCR panels for rapid detection of respiratory viral infections.Respiratory viral infections are one of the leading causes of morbidity and mortality, particularly in children, the elderly and immunocompromised persons. Rapid identification of viral etiology is critical in ruling out non-viral infections, initiating antiviral treatment and limiting the spread of the infection. Multiplex assays of more than one viral gene target in a single tube have the advantage of rapid screening of a large number of potential viral pathogens in a short time. A multiplex r ...201222052551
Human rhinoviruses in severe respiratory disease in very low birth weight infants.Objectives: To assess incidence, burden of illness, and risk factors for human rhinoviruses (HRVs) in a cohort of very low birth weight (VLBW) infants. Methods: A 2-year prospective cohort study was conducted among VLBW premature infants in Buenos Aires, Argentina. Infants were enrolled in the NICU from June 1, 2003, to May 31, 2005, and managed monthly and with every acute respiratory illness (ARI) during the first year of life. Nasal wash samples were obtained during every respiratory episode ...201222201153
Use of palivizumab in primary practice.Objective: To describe the implementation of a program for the use of palivizumab in a general pediatrics office and evaluate adherence to the 2009 American Academy of Pediatrics (AAP) guidelines. Methods: Pediatricians in a large practice were educated in the diagnosis and management of bronchiolitis, with specific attention to the AAP's palivizumab administration guidelines. During the 2009-2010 and 2010-2011 respiratory syncytial virus seasons, children were systematically identified and enr ...201222184649
A sensitive real-time PCR for detection and subgrouping of human respiratory syncytial virus.Improved diagnostic tools for rapid detection, quantitation, and subgrouping of human respiratory syncytial virus (RSV) are needed to aid the development and evaluation of novel intervention strategies. A quantitative real-time RT-PCR using specific locked nucleic acid (LNA) probes was developed to identify RSV and to distinguish RSV subgroups A and B (RSV LNA assay). RSV subgroup diversity and the relationship between viral load and disease severity in confirmed RSV infections were also explore ...201222119628
Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands.Respiratory syncytial virus (RSV) infection is the most important viral cause of severe respiratory disease in infants and children worldwide and also forms a serious threat in the elderly. The development of RSV vaccine, however, has been hampered by the disastrous outcome of an earlier trial using an inactivated and parenterally administered RSV vaccine which did not confer protection but rather primed for enhanced disease upon natural infection. Mucosal administration does not seem to prime f ...201222120195
Depletion of alveolar macrophages prolongs survival in response to acute pneumovirus infection.Alveolar macrophages are immunoregulatory effector cells that interact directly with respiratory virus pathogens in vivo. We examined the role of alveolar macrophages in acute infection with pneumonia virus of mice (PVM), a rodent pneumovirus that replicates the clinical sequelae of severe human respiratory syncytial virus disease. We show that PVM replicates in primary mouse macrophage culture, releasing infectious virions and proinflammatory cytokines. Alveolar macrophages isolated from PVM-in ...201222129848
Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions.The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8?µg/ml (0.41-22?nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6?µg/ ...201222028179
Purification of human respiratory syncytial virus fusion glycoprotein.Human respiratory syncytial virus (RSV) fusion glycoprotein (F) elicits neutralizing antibodies to RSV and has therefore attracted much attention as a suitable candidate antigen in the development of gene-based vaccines against RSV infections. However, a major obstacle in vaccine development has been the problem of antigen purification. To address this problem, we have developed a new method that combines sucrose gradient ultracentrifugation and a two-step chromatographic process, to purify RSV ...201221979254
increased replication of respiratory syncytial virus in the presence of cytokeratin 8 and 18.previously, it was reported that productive viral infection, viral protein synthesis, and viral rna replication of respiratory syncytial virus (rsv) operated efficiently in two human epithelial cell lines (hep-2 and a549), but not in a human mast-cell line, hmc-1. based on these observations, it was hypothesized that hmc-1 cells lack the machinery required for rsv replication. to identify the host factors required for rsv replication, cdna subtraction using a549, hep-2, and hmc-1 cells was perfo ...201222170560
microrna-221 modulates rsv replication in human bronchial epithelium by targeting ngf expression.early-life infection by respiratory syncytial virus (rsv) is associated with aberrant expression of the prototypical neurotrophin nerve growth factor (ngf) and its cognate receptors in human bronchial epithelium. however, the chain of events leading to this outcome, and its functional implications for the progression of the viral infection, has not been elucidated. this study sought to test the hypothesis that rsv infection modulates neurotrophic pathways in human airways by silencing the expres ...201222272270
jama patient page. respiratory syncytial virus bronchiolitis. 201222235094
different nf-κb activation characteristics of human respiratory syncytial virus subgroups a and b.human respiratory syncytial virus (hrsv) is a member of the family paramyxoviridae, and is responsible for serious respiratory illness in infants, the elderly and the immunocompromised. hrsv exists as two distinct lineages known as subgroups a and b, which represent two lines of divergent evolution with extensive genetic and serologic differences. while both subgroup a and b viruses contribute to overall hrsv disease, subgroup a isolates are associated with both increased frequency and morbidity ...201122212641
Structures of respiratory syncytial virus nucleocapsid protein from two crystal forms: details of potential packing interactions in the native helical form.Respiratory syncytial virus (RSV) is a frequent cause of respiratory illness in infants, but there is currently no vaccine nor effective drug treatment against this virus. The RSV RNA genome is encapsidated and protected by a nucleocapsid protein; this RNA-nucleocapsid complex serves as a template for viral replication. Interest in the nucleocapsid protein has increased owing to its recent identification as the target site for novel anti-RSV compounds. The crystal structure of human respiratory ...201122102022
Evidence for a Causal Relationship Between Allergic Sensitization and Rhinovirus Wheezing in Early Life.RATIONALE: Both aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood. OBJECTIVE: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing. METHODS: A total of 285 children at high-risk for allergic disease and asthma were followed prospectively from birth. The timing and etiology of viral respiratory wh ...201121960534
The innate antiviral factor APOBEC3G targets replication of measles, mumps, and respiratory syncytial virus.The cytidine deaminase APOBEC3G (apolipoprotein B mRNA-editing enzyme-catalytic polypeptide 3G; A3G) exerts antiviral activity against retroviruses, hepatitis B virus, adeno-associated virus, and transposable elements. We assessed whether the negative-strand (-)RNA viruses measles (MV), mumps (MuV), and respiratory syncytial virus (RSV) might be affected by A3G, and found that their infectivity was reduced by 1-2 logs (90-99%) in A3G over-expressing Vero cells, and in T cell lines expressing A3G ...201122170635
progress in respiratory virus vaccine development.viral respiratory infections cause significant morbidity and mortality in infants and young children as well as in at-risk adults and the elderly. although many viral pathogens are capable of causing respiratory disease, vaccine development has to focus on a limited number of pathogens, such as those that commonly cause serious lower respiratory illness (lri). whereas influenza virus vaccines have been available for some time (see the review by clark and lynch in this issue), vaccines against ot ...201121858754
Wheezing lower respiratory disease and vaccination of premature infants.Premature infants are at increased risk of wheezing in association with respiratory syncytial virus (RSV) and rhinovirus infections. We assess possible associations between wheezing and routine vaccinations of premature infants.201121875634
RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells.The cytokine interleukin-15 (IL-15), major histocompatibility complex (MHC) class I molecules and MHC class I chain-related proteins (MIC) A and B (MICA/B) are involved in cellular immune responses to virus infections but their role in respiratory syncytial virus (RSV) infection has not been studied. We aimed to determine how RSV infection modulates IL-15 production, MHC class I and MICA expression in respiratory epithelial cells, the molecular pathways implicated in virus-induced IL-15 producti ...201121852331
Neonatal CD8 T-cell Hierarchy Is Distinct from Adults and Is Influenced by Intrinsic T cell Properties in Respiratory Syncytial Virus Infected Mice.Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a predictable CD8+ T cell epitope hierarchy is established with a strongly dominant response to a K(d)-restricted peptide (SYIGSINNI) from the M2 protein. The response to K(d)M2(82-90) is ~5-fold higher than the response to a subdominant epitope from the M protein (NAITNAKII, D(b)M(187-195)). After infection of neonatal mice, a distinctly different epitope hierarchy emerges with codominant responses to K(d)M2(82-90) and ...201122144888
[Antibody responses induced by mucosal DNA vaccine encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium].In order to investigate antibody responses by musosal DNA vaccines encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium aroA strain SL7207 (SL7207) via intranasal or intragastric routes.201122043798
il-13 regulates th17 secretion of il-17a in an il-10-dependent manner.il-13 is a central mediator of airway hyperresponsiveness and mucus expression, both hallmarks of asthma. il-13 is found in the sputum of patients with asthma; therefore, il-13 is an attractive drug target for treating asthma. we have shown previously that il-13 inhibits th17 cell production of il-17a and il-21 in vitro. th17 cells are associated with autoimmune diseases, host immune responses, and severe asthma. in this study, we extend our in vitro findings and determine that il-13 increases i ...201122210911
effect of glucocorticoid in mice of asthma induced by ovalbumin sensitisation and rsv infection.to investigate the inflammatory changes and the airway hyper-responsiveness in the asthma mouse model infected by respiratory syncytial virus and elucidate the relationship between the infection and the effect of glucocorticoid.201121980833
Phase 1 Study of the Safety and Immunogenicity of a Live, Attenuated Respiratory Syncytial Virus and Parainfluenza Virus Type 3 Vaccine in Seronegative Children.BACKGROUND:: Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are important causes of lower respiratory tract illness and hospitalization in young children. Currently, there is no licensed vaccine against RSV or PIV3. METHODS:: In this randomized, phase 1, double-blind, placebo-controlled, dose-escalating study, 49 healthy RSV/PIV3-seronegative children 6 to <24 months of age were randomized 2:1 to receive 3 doses (at 104, 105, or 106 median tissue culture infective dose [ ...201121926667
nmegylation: a novel modification to enhance the bioavailability of therapeutic peptides.we have evaluated "nmegylation"--the covalent attachment of an oligo-n-methoxyethylglycine (nmeg) chain--as a new form of peptide/protein modification to enhance the bioavailability of short peptides. oligonmegs are hydrophilic polyethylene glycol-like molecules made by solid-phase synthesis, typically up to 40 monomers in length. they have been studied as nonfouling surface coatings and as monodisperse mobility modifiers for free-solution conjugate capillary electrophoresis. however, polynmegs ...201122180913
the anti-apoptotic effect of respiratory syncytial virus on human peripheral blood neutrophils is mediated by a monocyte derived soluble factor.respiratory syncytial virus (rsv) causes annual epidemics of respiratory disease particularly affecting infants. the associated airway inflammation is characterized by an intense neutrophilia. this neutrophilic inflammation appears to be responsible for much of the pathology and symptoms. previous work from our group had shown that there are factors within the airways of infants with rsv bronchiolitis that inhibit neutrophil apoptosis. this study was undertaken to determine if rsv can directly a ...201122046209
respiratory syncytial virus infection in adults.respiratory syncytial virus (rsv), an enveloped rna virus in the paramyxovirus family, is the most important cause of lower respiratory tract infection in infants and young children, accounting for ~100,000 pediatric hospitalizations and 250 deaths annually in the united states. despite primarily being recognized as a pediatric pathogen, rsv reinfection causes substantial disease in all adult populations, including healthy young persons, old and frail individuals, those with chronic obstructive ...201121858747
respiratory syncytial virus infection and the tight junctions of nasal epithelial cells.respiratory syncytial virus (rsv) primarily infects upper respiratory tract cells, mainly nasal epithelial cells. the tight junctions of nasal epithelial cells are thought to perform important innate immune function against foreign materials including respiratory viruses. we investigated in vitro the relationship of rsv infection and the tight junctions of primary nasal epithelial cells which had been transfected with human telomerase reverse transcriptase (htert) to prolong cell life. nasal epi ...201121865717
impact of respiratory syncytial virus: the nurse's perspective.respiratory syncytial virus (rsv) is a highly contagious virus, and is the major cause of lower respiratory tract infections in infants and toddlers worldwide. rsv infection poses serious health risks to young children during the first 2 years of life. several infant populations have been classified as high risk, and additional risk factors are known to increase the likelihood of severe rsv infection. treatment for active rsv infection is limited to the symptoms of infection rather than the unde ...201121902285
relationship between the population incidence of febrile convulsions in young children in sydney, australia and seasonal epidemics of influenza and respiratory syncytial virus, 2003-2010: a time series analysis.in 2010, intense focus was brought to bear on febrile convulsions in australian children particularly in relation to influenza vaccination. febrile convulsions are relatively common in infants and can lead to hospital admission and severe outcomes. we aimed to examine the relationships between the population incidence of febrile convulsions and influenza and respiratory syncytial virus (rsv) seasonal epidemics in children less than six years of age in sydney australia using routinely collected s ...201122029484
impact of influenza during the post-pandemic season: epidemiological picture from syndromic and virological surveillance.following the observation that 1 or 2 pandemic peak due to the circulation ofahinlv had occurred in most countries and in most world health organization (who) regions, who declared on august 10"h, 2010 that the world was moving into the post-pandemic period, whose surveillance presents considerable interest both from epidemiological and clinical point of view. we described the epidemiological picture emerged from syndromic and virological surveillance during the post-pandemic season in liguria, ...201122010543
Molecular epidemiology of the SH (small hydrophobic) gene of human respiratory syncytial virus (HRSV), over 2 consecutive years.Human respiratory syncytial virus (HRSV) strains were isolated from nasopharyngeal aspirates collected from 965 children between 2004 and 2005, yielding 424 positive samples. We sequenced the small hydrophobic protein (SH) gene of 117 strains and compared them with other viruses identified worldwide. Phylogenetic analysis showed a low genetic variability among the isolates but allowed us to classify the viruses into different genotypes for both groups, HRSVA and HRSVB. It is also shown that the ...201121893117
serosurvey of bacterial and viral respiratory pathogens among deployed u.s. service members.respiratory illnesses can cause substantial morbidity during military deployments. bordetella pertussis, chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, parainfluenza, and respiratory syncytial virus (rsv) are hypothesized causes.201122099233
relationship between lower respiratory tract infections caused by respiratory syncytial virus and subsequent development of asthma in japanese children.several studies in western countries have found that lower respiratory tract infections (lrtis) caused by the respiratory syncytial virus (rsv) in infancy may subsequently trigger the development of asthma. in this study, we enrolled 262 infants under the age of 3 who had been admitted to our hospital with lrti between september 2002 and august 2003. rsv infection was diagnosed in these patients using an rsv rapid diagnostic kit and by measuring antibody titers in paired serum samples. in march ...201121937828
The insertion of fluorescent proteins in a variable region of respiratory syncytial virus L polymerase results in fluorescent and functional enzymes but with reduced activities.The respiratory syncytial virus (RSV) Large protein L is the catalytic subunit of the RNA-dependent RNA polymerase complex. Currently, no structural information is available for RSV L. Sequence alignments of L protein from human and bovine strains of RSV revealed the existence of two variable regions, VR1 and VR2. Following comparison with morbillivirus and rhabdovirus L genes, VR2, which is located between domains V and VI, was chosen as an insertion site for sequences encoding the epitope tag ...201121966341
[Etiology survey on virus of acute respiratory infection in Guangzhou from 2006 to 2009].To investigate the pathogens of acute respiratory infection (ARI) in Guangzhou from 2006 to 2009.201122177307
Phylogenetic analysis of bovine respiratory syncytial viruses from recent outbreaks in feedlot and dairy cattle herds.Bovine respiratory syncytial virus (BRSV) is one of the major causes of bovine respiratory disease worldwide. In order to study the molecular epidemiology of the virus, samples from 30 BRSV outbreaks in cattle herds located in different parts of Sweden were collected from 2007 to 2011. The samples were analyzed by PCR, and the glycoprotein (G) gene was sequenced. BRSV was detected in outbreaks of respiratory disease in both dairy and feedlot herds most often during the winter period but also dur ...201122209787
age-related increases in pgd(2) expression impair respiratory dc migration, resulting in diminished t cell responses upon respiratory virus infection in mice.the morbidity and mortality associated with respiratory virus infection is felt most keenly among the elderly. t cells are necessary for viral clearance, and many age-dependent intrinsic t cell defects have been documented. however, the development of robust t cell responses in the lung also requires respiratory dcs (rdcs), which must process antigen and migrate to draining lns (dlns), and little is known about age-related defects in these t cell-extrinsic functions. here, we show that increases ...201122105170
comparison of the filmarray respiratory panel and prodesse real-time pcr assays for detection of respiratory pathogens.we compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the filmarray respiratory panel (rp) multiplex pcr assay (idaho technology, inc., salt lake city, ut) with those of the food and drug administration (fda)-cleared prodesse proflu+, profast+, proparaflu+, pro hmpv+, and proadeno+ real-time pcr assays (gen-probe, san diego, ca). the assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children u ...201121998418
ten years of human metapneumovirus research.described for the first time in 2001, human metapneumovirus (hmpv) has become one of the main viral pathogens responsible for acute respiratory tract infections in children but also in the elderly and immuno-compromised patients. the pathogen most closely related to hmpv is human respiratory syncytial virus (hrsv), the most common cause of bronchiolitis and pneumonia in young children. hmpv has been classified into two main viral groups a and b and has a seasonal distribution in temperate countr ...201122074934
respiratory syncytial virus--united states, july 2007-june 2011.each year in the united states, an estimated 75,000-125,000 hospitalizations related to respiratory syncytial virus (rsv)occur among children aged <1 year, and rsv infection results in approximately 1.5 million outpatient visits among children aged <5 years. in the united states, rsv season begins in the fall, peaks in winter, and ends in the late winter and early spring. however, the exact timing and duration vary from year to year and by geographic region. to describe trends in rsv seasonality ...201121900874
[pilot study: serological research of bovine respiratory syncytial virus and mannheimia haemolytica in young cattle at dairy farms in the netherlands]. 201121870575
local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze.respiratory syncytial virus (rsv) is the most common cause of bronchiolitis in infants. following rsv bronchiolitis, 50% of children develop post-bronchiolitis wheeze (pbw). animal studies have suggested that interleukin (il)-10 plays a critical role in the pathogenesis of rsv bronchiolitis and subsequent airway hyperresponsiveness. previously, we showed that ex vivo monocyte il-10 production is a predictor of pbw. additionally, heterozygosity of the single-nucleotide polymorphism (snp) rs180087 ...201121910858
Slowing down with age: lung DCs do it too.Decline in immune function with age has been attributed to defects or alterations in both the innate and the adaptive immune system. In this issue of the JCI, Zhao and coworkers provide evidence for a novel mechanism of immune dysfunction in aging mice. They show that migration of respiratory DCs from the site of virus replication to the draining lymph nodes in response to infection with several different respiratory viruses is markedly diminished with increasing age. The impaired DC migration w ...201122105176
Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus Infection in High-risk Children, Based on Long-term Epidemiologic Data From Austria.: To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria.201121960187
Picornavirus - the Most Common Respiratory Virus Infection among Patients of All Ages Hospitalized with Acute Respiratory Illness.We evaluated the prevalence of respiratory virus infection (RVI) in 403 illnesses of persons hospitalized over a 2-year period with acute respiratory conditions using virus-specific RT-PCR assays in addition to cell culture and serology. RVIs were identified in >75% of children under 5 years and 25-37% of adults. The molecular assays doubled the number of infections identified; picornaviruses were the most frequent in patients of all ages, followed by respiratory syncytial virus and influenza vi ...201122116142
human metapneumovirus inhibits ifn-β signaling by downregulating jak1 and tyk2 cellular levels.human metapneumovirus (hmpv), a leading cause of respiratory tract infections in infants, inhibits type i interferon (ifn) signaling by an unidentified mechanism. in this study, we showed that infection of airway epithelial cells with hmpv decreased cellular level of janus tyrosine kinase (jak1) and tyrosine kinase 2 (tyk2), due to enhanced proteosomal degradation and reduced gene transcription. in addition, hmpv infection also reduced the surface expression of type i ifn receptor (ifnar). these ...201121949722
clinical impact of rt-pcr for pediatric acute respiratory infections: a controlled clinical trial.real-time polymerase chain reaction (rt-pcr) testing is a quick sensitive method for detecting respiratory pathogens. we evaluated the diagnostic yield of rt-pcr assays and measured the effect of rapid reporting on patient care.201121987698
sendai virus-based rsv vaccine protects african green monkeys from rsv infection.respiratory syncytial virus (rsv) is a serious disease of children, responsible for an estimated 160,000 deaths per year worldwide. despite the ongoing need for global prevention of rsv and decades of research, there remains no licensed vaccine. sendai virus (sev) is a mouse parainfluenza virus-type 1 which has been previously shown to confer protection against its human cousin, human parainfluenza virus-type 1 in african green monkeys (agm). here is described the study of a rsv vaccine (sevrsv) ...201122119594
the prophylaxis and treatment with antiviral agents of respiratory syncytial virus infections.in this review, we consider recent advances in the discovery and development of antiviral agents for respiratory syncytial virus (rsv) infections. a background to the various manifestations of human rsv infection and current treatments is provided. the technical, clinical and commercial issues surrounding the development of such antiviral agents are discussed.201122182737
Label-free quantitative proteomics reveals regulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and 5'-3'-exoribonuclease 2 (XRN2) during respiratory syncytial virus infection.ABSTRACT: A large quantitative study was carried out to compare the proteome of respiratory syncytial virus (RSV) infected versus uninfected cells in order to determine novel pathways regulated during viral infection. RSV infected and mock-infected HEp2 cells were lysed and proteins separated by preparative isoelectric focussing using offgel fractionation. Following tryptic digestion, purified peptides were characterized using label-free quantitative expression profiling by nano-ultra performanc ...201121933386
interaction of enterovirus infection and cow's milk-based formula nutrition in type 1 diabetes-associated autoimmunity.background: enteral virus infections and early introduction of cow's milk (cm)-based formula are among the suggested triggers of type 1 diabetes (t1d)- associated autoimmunity, although studies on their role have remained contradictory. here, we aimed to analyse whether interactions between these factors might clarify the controversies. materials: the study population comprised 107 subjects developing positivity for at least two t1d-associated autoantibodies and 446 control subjects from the fin ...201121922634
[Detection of bovine respiratory syncytial virus by RT-PCR].The paper presents the results of studying the diagnostic efficiency of RT-PCR for the detection of respiratory syncytial virus in cattle of different ages. Glycoprotein F gene sequences were used as a target for amplification. The sensitivity of the reaction was 10 TCD50/ml and the virus detection rate in biomaterials averaged 19%. samples. That in RT-PCR correlated with the presence of clinical signs in sick animals.201122171476
antiviral activity in vitro of two preparations of the herbal medicinal product sinupret® against viruses causing respiratory infections.sinupret(®), a herbal medicinal product made from gentian root, primula flower, elder flower, sorrel herb, and verbena herb is frequently used in the treatment of acute and chronic rhinosinusitis and respiratory viral infections such as common cold. to date little is known about its potential antiviral activity. therefore experiments have been performed to measure the antiviral activity of sinupret(®) oral drops (hereinafter referred to as "oral drops") and sinupret(®) dry extract (hereinafter r ...201122112724
whole genome sequencing and evolutionary analysis of human respiratory syncytial virus a and b from milwaukee, wi 1998-2010.respiratory syncytial virus (rsv) is the leading cause of lower respiratory-tract infections in infants and young children worldwide. despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for rsv group a and group b respectively.201121998661
natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection.it is known that respiratory syncytial virus (rsv) is the main cause of bronchiolitis and pneumonia in young children. rsv infection often leads to severe acute lung immunopathology, but the underlying immune mechanisms are less elucidated. here, we found that rsv infection induced severe acute lung immune injury and promoted the accumulation and activation of lung natural killer (nk) cells at the early stage of infection in balb/c mice. activated lung nk cells highly expressed activating recept ...201122171263
inosine-containing rna is a novel innate immune recognition element and reduces rsv infection.during viral infections, single- and double-stranded rna (ssrna and dsrna) are recognized by the host and induce innate immune responses. the cellular enzyme adar-1 (adenosine deaminase acting on rna-1) activation in virally infected cells leads to presence of inosine-containing rna (ino-rna). here we report that ss-ino-rna is a novel viral recognition element. we synthesized unmodified ssrna and ssrna that had 6% to16% inosine residues. the results showed that in primary human cells, or in mice ...201122028885
Effectiveness of palivizumab prophylaxis in infants and children in Florida.PURPOSE: Palivizumab effectiveness data on respiratory syncytial virus (RSV) infections are limited to trial settings and vary considerably between selected high-risk populations. This study aimed to evaluate effectiveness in a community-based sample. METHODS: We conducted a cohort study of children with =3?months Florida Medicaid fee-for-service eligibility between 1998 and 2004 who also had matching birth certificates. Children entered the cohort at the beginning of the RSV season, after a min ...201121919115
evaluation of protective efficacy of respiratory syncytial virus vaccine against a and b subgroup human isolates in korea.human respiratory syncytial virus (hrsv) is a significant cause of upper and lower respiratory tract illness mainly in infants and young children worldwide. hrsv is divided into two subgroups, hrsv-a and hrsv-b, based on sequence variation within the g gene. despite its importance as a respiratory pathogen, there is currently no safe and effective vaccine for hrsv. in this study, we have detected and identified the hrsv by rt-pcr from nasopharyngeal aspirates of korean pediatric patients. intere ...201121915262
natural polymorphisms and resistance-associated mutations in the fusion protein of respiratory syncytial virus (rsv): effects on rsv susceptibility to palivizumab.specific mutations in respiratory syncytial virus (rsv) fusion protein can cause palivizumab resistance. we assessed the incidence of sequence polymorphisms and palivizumab resistance in clinical rsv isolates collected from immunoprophylaxis-naive subjects. polymorphisms were identified at low frequency, and only polymorphic mutations in antigenic site a (<1% of all polymorphisms) conferred palivizumab resistance.201122184728
reduced inflammation and altered innate response in neonates during paramyxoviral infection.abstract: background: human infants are frequently hospitalized due to infection with the paramyxovirus respiratory syncytial virus (rsv). however, very little is known about the neonatal response to paramyxoviral infection. here, a neonatal model of paramyxoviral infection is developed using the mouse pathogen sendai virus (sev). results: adult mice infected with sev developed a predominantly neutrophilic inflammatory cell influx and a concomitant reduction in lung function, as determined by ...201122185352
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