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a sensitive, specific, and cost-effective multiplex reverse transcriptase-pcr assay for the detection of seven common respiratory viruses in respiratory samples.cell culture and direct fluorescent antibody (dfa) assays have been traditionally used for the laboratory diagnosis of respiratory viral infections. multiplex reverse transcriptase polymerase chain reaction (m-rt-pcr) is a sensitive, specific, and rapid method for detecting several dna and rna viruses in a single specimen. we developed a m-rt-pcr assay that utilizes multiple virus-specific primer pairs in a single reaction mix combined with an enzyme-linked amplicon hybridization assay (elaha) u ...200415096568
enhanced adherence of streptococcus pneumoniae to human epithelial cells infected with respiratory syncytial virus.in the present study, we analyzed the effect of a preceding respiratory syncytial virus (rsv) infection of human respiratory epithelial cells on the adherence of streptococcus pneumoniae tested by means of a cytometric fluorescence assay. adherence of clinically relevant pneumococcal serotypes 3, 9, 14, 18, 19, and 23 was studied using uninfected and rsv-infected monolayers. to this end, monolayers of both human nasopharyngeal cells (hep-2) and pneumocyte type ii cells (a549) were infected with ...200415103015
antiviral flavonoids from the seeds of aesculus chinensis.a bioassay-guided fractionation of an ethanol extract of the seeds of aesculus chinensis led to the isolation of two new flavanoids (1 and 2), along with eight known ones (3-10). the structures of the new compounds were elucidated by spectroscopic methods including 2d nmr. all compounds were tested for antiviral activity against respiratory syncytial virus (rsv), parainfluenza virus type 3 (piv 3), and influenza virus type a (flu a). compounds 1, 2, and 6 showed significant antiviral activities ...200415104496
efficacy of novel hemagglutinin-neuraminidase inhibitors bcx 2798 and bcx 2855 against human parainfluenza viruses in vitro and in vivo.human parainfluenza viruses are important respiratory tract pathogens, especially of children. however, no vaccines or specific therapies for infections caused by these viruses are currently available. in the present study we characterized the efficacy of the novel parainfluenza virus inhibitors bcx 2798 and bcx 2855, which were designed based on the three-dimensional structure of the hemagglutinin-neuraminidase (hn) protein. the compounds were highly effective in inhibiting hemagglutinin (ha) a ...200415105096
anti-respiratory syncytial virus (rsv) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyperresponsiveness in a murine rsv model.numerous studies have described a strong association between respiratory syncytial virus (rsv) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. we evaluated the effect of an anti-rsv neutralizing monoclonal antibody (palivizumab) on different aspects of rsv disease by using a murine model. balb/c mice were intranasally inoculated with rsv a2. palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h afte ...200415105140
the small hydrophobic (sh) protein accumulates within lipid-raft structures of the golgi complex during respiratory syncytial virus infection.the cellular distribution of the small hydrophobic (sh) protein in respiratory syncytial virus (rsv)-infected cells was examined. although the sh protein was distributed throughout the cytoplasm, it appeared to accumulate in the golgi complex within membrane structures that were enriched in the raft lipid, gm1. the ability of the sh protein to interact with lipid-raft membranes was further confirmed by examining its detergent-solubility properties in triton x-100 at 4 degrees c. this analysis sh ...200415105532
comparison of clinical characteristics of influenza and respiratory syncytial virus infection in hospitalised children and adolescents.while significant morbidity due to respiratory syncytial virus (rsv) infection in the paediatric population has been well acknowledged, little is known about the burden of influenza in primarily healthy children in europe. in our institution, a university children's hospital in switzerland, medical staff were encouraged to take nasopharyngeal specimens for multiplex polymerase chain reaction assays for influenza a and b, rsv and several other pathogens from patients hospitalised with respiratory ...200415106003
major histocompatibility (b) complex control of responses against rous sarcomas.the chicken major histocompatibility (b) complex (mhc) affects disease outcome significantly. one of the best characterized systems of mhc control is the response to the oncogenic retrovirus, rous sarcoma virus (rsv). genetic selection altered the tumor growth pattern, either regressively or progressively, with the data suggesting control by one or a few loci. particular mhc genotypes determine rsv tumor regression or progression indicating the crucial b complex role in rous sarcoma outcome. ana ...200415109061
influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination.the annual hajj pilgrimage to mecca, saudi arabia brings over two million people to a small confined area. respiratory tract infection is the most common disease transmitted during this period. for most of the etiologic agents of upper respiratory tract infections, no vaccine or prophylaxis is available, except for influenza. yearly influenza vaccination of high-risk groups is recommended, but no special recommendations are available for those performing the hajj or other similar large congregat ...200415109471
rhoa-derived peptide dimers share mechanistic properties with other polyanionic inhibitors of respiratory syncytial virus (rsv), including disruption of viral attachment and dependence on rsv g.large polyanionic molecules, such as sulfated polysaccharides (including soluble heparin and dextran sulfate), synthetic polyanionic polymers, and negatively charged proteins, have been shown to broadly inhibit several enveloped viruses. we recently reported the antiviral activity of a peptide derived from amino acids 77 to 95 of a potential binding partner of respiratory syncytial virus f protein (rsv f), the gtpase rhoa. a subsequent study with a truncated peptide (amino acids 80 to 94) reveal ...200415113882
unspliced rous sarcoma virus genomic rnas are translated and subjected to nonsense-mediated mrna decay before packaging.retroviruses package full-length, unspliced rnas into progeny virions as dimerized rna genomes. they also use unspliced rnas as mrnas to produce the gag and pol gene products. we asked whether a single rous sarcoma virus (rsv) rna can be translated and subsequently packaged or whether genomic packaging requires a nontranslated population of rnas. we addressed this issue by utilizing the translation-dependent nonsense-mediated mrna decay (nmd) pathway. nmd is the selective destruction of mrnas be ...200415113896
optimizing long-term care by administration of influenza vaccine to parents of nicu patients.the neonatal intensive care unit (nicu) team has traditionally invested itself in maintaining the health of its patients upon discharge from high-acuity care. historically, this has included the administration of vaccinations to the patients and more recently, palivizumab--a monoclonal antibody directed against respiratory synctial virus (rsv). with increasing awareness of the ill-effects associated with influenza virus and recommendations those in close contact with high-risk infants receive th ...200415116124
respiratory syncytial virus induces pneumonia, cytokine response, airway obstruction, and chronic inflammatory infiltrates associated with long-term airway hyperresponsiveness in mice.respiratory syncytial virus (rsv) infection is associated with acute morbidity (e.g., pneumonia and airway obstruction [ao]) and long-term complications (e.g., airway hyperresponsiveness [ahr]). we present a comprehensive evaluation of the acute and chronic phases of rsv respiratory tract infection, using a mouse model.200415122522
timing of infection and prior immunization with respiratory syncytial virus (rsv) in rsv-enhanced allergic inflammation.respiratory syncytial virus (rsv) infection has been shown to be a risk factor for the development of allergy in humans and mice. the allergy-enhancing properties of rsv may be dependent on atopic background and an individual's history of rsv infection. we examined the influence of the timing of infection and prior inoculation with rsv in a mouse model of allergic asthma. mice were sensitized to and challenged with ovalbumin (ova) and were inoculated with rsv either before or during the sensitiz ...200415122523
production of interferon gamma in respiratory syncytial virus infection of humans is not associated with interleukins 12 and 18.in order to understand early events in the immune response to respiratory syncytial virus (rsv) infection, we studied the presence of various chemokines and cytokines in respiratory secretions of human infants with rsv infection. interferon gamma (ifngamma) was present in 30/39 (76.9%) subjects tested, but the ifngamma-inducing cytokines interleukin (il)12 and il18 were detectable in 6/40 (15%) and 11/38 (28.9%) subjects, respectively. quantities of il12 and il18 did not correlate with those of ...200415122806
age related differences in humoral immune response to respiratory syncytial virus infection in adults.the humoral immune response to respiratory syncytial virus (rsv) was investigated in old and young adults. rsv was identified by culture and/or reverse transcription polymerase chain reaction (rt-pcr) in 52 elderly (mean age 74 years) and 15 young adults (mean age 33 years) with respiratory illness. preinfection serum neutralizing and binding antibody levels were similar in the two age groups, although older persons had significantly greater serum neutralizing responses to group a rsv (log(2) 2. ...200415122807
inhibition of respiratory syncytial virus infection with the cc chemokine rantes (ccl5).respiratory syncytial virus (rsv) is a major cause of respiratory tract disease in infants, aged adults, and immunosuppressed patients. the only approved medicines for rsv disease are administration of prophylatic antibodies or treatment with a synthetic nucleoside. both approaches are expensive and the latter is not without risk and of controversial benefit. the present investigation studied whether pharmaceutical or biologic compounds based upon chemokines might be useful in preventing rsv dis ...200415122808
new drugs and treatment for respiratory syncytial virus.the respiratory syncytial virus (rsv) is a global health problem affecting infants and the elderly and claiming more lives than aids in many parts of the world. only two antibody drugs are approved for its prevention, and ribavarin, a relatively nonspecific antiviral, is used for treatment. in the mid-1990s, a number of pharmaceutical and biotech companies initiated research programs against rsv. together, the academic and the industrial r&d covered the whole spectrum of antibodies, vaccines, sy ...200415124232
antiviral drugs in current clinical use.the current armamentarium for the chemotherapy of viral infections consists of 37 licensed antiviral drugs. for the treatment of human immunodeficiency virus (hiv) infections, 19 compounds have been formally approved: (i) the nucleoside reverse transcriptase inhibitors (nrtis) zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; (ii) the nucleotide reverse transcriptase inhibitor (ntrti) tenofovir disoproxil fumarate; (iii) the non-nucleoside reverse transcript ...200415125867
evaluation of a multiplex reverse transcriptase pcr elisa for the detection of nine respiratory tract pathogens.a multiplex reverse transcription (rt) polymerase chain reaction combined with a microwell hybridization assay (m-rt-pcr-elisa) was previously developed to detect nine different microorganisms: enterovirus (ev), influenza virus type a (iva) and type b (ivb), respiratory syncytial virus (rsv), parainfluenzavirus type 1 (piv1) and type 3 (piv3), adenovirus (av), mycoplasma pneumoniae (mpn), chlamydia pneumoniae (cpn) in a single test. these organisms do not usually colonize the respiratory tract o ...200415125873
respiratory syncytial virus in allergic lung inflammation increases muc5ac and gob-5.respiratory syncytial virus (rsv) is associated with wheezing and childhood asthma. we previously reported that rsv infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin (ova)-sensitized mice. in addition, allergically sensitized rsv-infected (ova/rsv) mice had more abundant airway epithelial mucus production compared with ova mice 14 days after infection, whereas there was almost no mucus in mice that were only rsv infected. we hypothesized that this increased mucus wa ...200415130904
genetic variability and molecular epidemiology of respiratory syncytial virus subgroup a strains in japan determined by heteroduplex mobility assay.we used heteroduplex mobility assay (hma) to determine the genetic variability of 118 respiratory syncytial virus (rsv) field isolates from 19 epidemics occurring in a japanese urban area between 1980 and 2000. nucleotides 1 to 584 of the attachment g glycoprotein gene were amplified by reverse transcription-pcr, and the pcr amplicons were analyzed by hma by using the earliest isolate from 1980 as the reference throughout. we also performed pcr-restriction fragment length polymorphism (rflp) ana ...200415131169
impact of wheezing after respiratory syncytial virus infection on health-related quality of life.respiratory syncytial virus (rsv) lower respiratory tract infection (lrti) is often followed by recurrent wheezing episodes during childhood. the effect of postbronchiolitis wheezing on the well-being of the child is not known. this study aimed to determine the impact of rsv lrti hospitalization before age 13 months on health-related quality of life (hrqol) at age 3 years.200415131463
driscoll children's hospital respiratory syncytial virus database: risk factors, treatment and hospital course in 3308 infants and young children, 1991 to 2002.treatment of respiratory syncytial virus (rsv) lower respiratory tract infection has historically been one of the most frequent reasons for admission to driscoll children's hospital.200415131464
[the anti-respiratory syncytial virus effect of an active compound (ap3) from a chinese medicinal herb-herba patriniae in vitro].to study the effect on anti-respiratory syncytial virus of an active compound (ap3) from a chinese medicinal herb-herba patriniae in vitro.200415132871
human metapneumovirus as a causative agent of acute bronchiolitis in infants.human metapneumovirus (hmpv), has been recently isolated from children with acute respiratory tract infections (rtis), including bronchiolitis, and classified in the pneumovirinae subfamily within the paramyxoviridae family.200415135747
recombinant respiratory syncytial viruses lacking the c-terminal third of the attachment (g) protein are immunogenic and attenuated in vivo and in vitro.the design of attenuated vaccines for respiratory syncytial virus (rsv) historically focused on viruses made sensitive to physiologic temperature through point mutations in the genome. these prototype vaccines were not suitable for human infants primarily because of insufficient attenuation, genetic instability, and reversion to a less-attenuated phenotype. we therefore sought to construct novel attenuated viruses with less potential for reversion through genetic alteration of the attachment g p ...200415140975
respiratory syncytial virus (rsv) g glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated rsv.following respiratory syncytial virus (rsv) challenge, mice immunized with rsv g or with formalin-inactivated rsv (fi-rsv) exhibit severe disease associated with type 2 cytokine production and pulmonary eosinophilia. this has led to the proposal that the presence of rsv g is the factor in fi-rsv that induces disease-enhancing t-cell responses. therefore, we evaluated the role of rsv g and its immunodominant region in the induction of aberrant immune responses during fi-rsv immunization. balb/c m ...200415141000
recombinant sendai virus expressing the g glycoprotein of respiratory syncytial virus (rsv) elicits immune protection against rsv.although rsv causes serious pediatric respiratory disease, an effective vaccine does not exist. to capture the strengths of a live virus vaccine, we have used the murine parainfluenza virus type 1 (sendai virus [sv]) as a xenogeneic vector to deliver the g glycoprotein of rsv. it was previously shown (j. l. hurwitz, k. f. soike, m. y. sangster, a. portner, r. e. sealy, d. h. dawson, and c. coleclough, vaccine 15:533-540, 1997) that intranasal sv protected african green monkeys from challenge wit ...200415141002
differential production of inflammatory cytokines in primary infection with human metapneumovirus and with other common respiratory viruses of infancy.viral respiratory infections are the most frequent cause of hospital admission for infants and young children during winter. however, the mechanisms of illness that are associated with viral lower-respiratory-tract infection (lri) are unclear. a widely accepted hypothesis attributes the pathogenesis of viral lri in infants to the induction of innate inflammatory responses. this theory is supported by studies showing that toll-like receptor 4 is activated by respiratory syncytial virus (rsv), lea ...200415143472
association between common toll-like receptor 4 mutations and severe respiratory syncytial virus disease.the clinical spectrum of respiratory syncytial virus (rsv) bronchiolitis in previously healthy infants is extremely variable. thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. toll-like receptor 4 (tlr4) and cd14 are part of a receptor complex involved in the innate immune response to rsv.200415143473
genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis.the nature of the association between severe respiratory syncytial virus (rsv) bronchiolitis and subsequent wheezing remains unknown. in a previous study, we showed that genetic variation in the il-8-promoter region is associated with susceptibility to severe bronchiolitis.200415144474
pulmonary delivery of respiratory syncytial virus dna vaccines using macroaggregated albumin particles.at present there is no safe and effective vaccine for respiratory syncytial virus (rsv). dna vaccines encoding rsv surface glycoproteins are one option being examined. current methods to deliver dna vaccines generally require repeated high dose intramuscular or intradermal administration for effectiveness. in this study, we examine the efficacy of pulmonary dna vaccination using low dose dna vaccines encoding the rsv f glycoprotein conjugated to macroaggregated albumin (maa-f). single vaccinatio ...200415149784
selection of functional mutations in the u5-ir stem and loop regions of the rous sarcoma virus genome.the 5' end of the rous sarcoma virus (rsv) rna around the primer-binding site forms a series of rna secondary stem/loop structures (u5-ir stem, tpsic interaction region, u5-leader stem) that are required for efficient initiation of reverse transcription. the u5-ir stem and loop also encode the u5 integrase (in) recognition sequence at the level of dna such that this region has overlapping biological functions in reverse transcription and integration.200415153244
lower respiratory tract illness and rsv prophylaxis in very premature infants.to determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (lrti) and for respiratory syncytial virus (rsv) documented lrti in children born very prematurely who had or had not received rsv prophylaxis.200415155404
evaluation of bbg2na in infant macaques: specific immune responses after vaccination and rsv challenge.we have addressed the safety of alum-adsorbed bbg2na, a recombinant respiratory syncytial virus (rsv) subunit vaccine, in infant macaques. animals received two vaccinations, and were challenged 4 months later with rsv. in two of four bbg2na-vaccinated animals, specific il-13 producing t cells were detected. upon challenge, low level pulmonary eosinophilia was observed in the same two animals. although the levels of these responses were substantially lower than those observed in the fi-rsv contro ...200415161068
vaccination of infant macaques with a recombinant modified vaccinia virus ankara expressing the respiratory syncytial virus f and g genes does not predispose for immunopathology.we have evaluated the safety and immunogenicity of a recombinant modified vaccinia virus ankara (mva) vector expressing the respiratory syncytial virus (rsv) fusion (f) and attachment (g) proteins in infant macaques. animals were vaccinated twice and 4 months later challenged with rsv. although vaccination did not predispose for immunopathology upon challenge, we were also unable to demonstrate protection. since vaccination had resulted in priming for secondary immune responses upon challenge, w ...200415161069
biochemical characterization of the respiratory syncytial virus p-p and p-n protein complexes and localization of the p protein oligomerization domain.the rna-dependent rna polymerase complex of respiratory syncytial virus (rsv) is composed of the large polymerase (l), the phosphoprotein (p), the nucleocapsid protein (n) and the co-factors m2-1 and m2-2. the p protein plays a central role within the replicase-transcriptase machinery, forming homo-oligomers and complexes with n and l. in order to study p-p and n-p complexes, and the role of p phosphorylation in these interactions, the human rsv p and n proteins were expressed in e. coli as his- ...200415166449
isolation and characterization of nmso3-resistant mutants of respiratory syncytial virus.we obtained two mutant strains of respiratory syncytial virus (rsv) which showed resistance against nmso3 after 15 and 33 passages, respectively, in hep-2 cells in the presence of 6.8 microm of nmso3. the ec50 values of nmso3 for the resistant virus strains were 0.48 and 0.93 microm, that is 4.8-9.3 times higher than that of the parent strain (ec50 = 0.1 microm). the most resistant strain also showed resistance against heparin but was sensitive to dextran sulfate and a polyoxotungstate, pm-523. ...200415168797
potent inhibition of respiratory syncytial virus by combination treatment with 2-5a antisense and ribavirin.respiratory syncytial virus (rsv) is a major cause of lower respiratory diseases in infants, young children, and the elderly. ribavirin, the only currently approved drug for the treatment of rsv infections in the u.s., requires high doses to be effective. therefore, it has only a limited clinical efficacy in the treatment of rsv infections. it has been shown that a cellular ribonuclease, rnase l, can be recruited by 2'-5' linked tetra-adenylates (2-5a) attached to an antisense sequence complemen ...200415168801
seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection.it is well known that respiratory syncytial virus (rsv) lower respiratory tract infection (lrti) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following rsv lrti is not known. this study aimed to determine the continuous development of wheezing following rsv lrti in children up to the age of 3 years.200415170037
enhanced virulence, airway inflammation and impaired lung function induced by respiratory syncytial virus deficient in secreted g protein.respiratory syncytial virus (rsv) infection can cause bronchial hyperresponsiveness and asthma exacerbations. in mice it results in airway inflammation and airway hyperresponsiveness. since viral factors influencing these responses are not well defined, a study was undertaken to investigate the role of secreted g protein of human rsv in determining virulence, inflammatory responses, and changes in lung function.200415170038
palivizumab: a review of its use as prophylaxis for serious respiratory syncytial virus infection.palivizumab (synagi) is a humanized monoclonal antibody that provides immunoprophylaxis against serious lower respiratory tract infections (lrtis) caused by respiratory syncytial virus (rsv). rsv is the leading cause of hospitalization for lrtis in infants, causing winter- or wet-season epidemics. in two double-blind, placebo-controlled trials, intramuscular palivizumab 15 mg/kg every 30 days for 5 months significantly reduced rsv-related hospitalizations by 55% in 1502 infants with prematurity ...200415170364
human metapneumovirus infection in hospital referred south african children.human metapneumovirus (hmpv) was first described in dutch children with acute respiratory symptoms. a prospective analysis of the epidemiology, clinical manifestation, and seroprevalence of hmpv and other respiratory viruses in south african children referred to hospital for upper or lower respiratory tract infection were carried out during a single winter season, by using rt-pcr, viral culture, and enzyme-linked immunosorbent assays. in nasopharyngeal aspirates from 137 children, hmpv was detec ...200415170647
risk of serious bacterial infection in young febrile infants with respiratory syncytial virus infections.the evaluation of young febrile infants is controversial, in part because it is unclear whether clinical evidence of a viral infection significantly reduces the risk of serious bacterial infections (sbis). specifically, it remains unclear whether the risk of sbi is altered in a meaningful way in the presence of respiratory syncytial virus (rsv) infections.200415173498
population-based surveillance for hospitalizations associated with respiratory syncytial virus, influenza virus, and parainfluenza viruses among young children.respiratory syncytial virus (rsv), influenza virus, and parainfluenza viruses (piv) cause significant morbidity in young children. although only influenza virus infection and illness is currently vaccine-preventable, vaccines are under development for rsv and piv. we established a prospective, active population-based surveillance network to provide precise estimates of hospitalization rates for viral acute respiratory illness (ari) in young children and to measure the potential impact of enhance ...200415173503
aetiology of acute pharyngitis: the role of atypical bacteria.in order to establish the role of atypical bacteria and compare characteristics of different infectious agents in acute pharyngitis, 127 patients with acute pharyngitis (66 males; median age, 5.33 years; range, 6 months to 14 years) and 130 healthy subjects of similar sex and age were studied. serology with paired samples and pcr on nasopharyngeal aspirates and throat cultures were used to identify bacteria and viruses. viruses were identified in 43 patients (33.8%) and five controls (3.8%; p < ...200415184536
[clinical characteristics of bronchiolitis caused by human metapneumovirus in infants].the fact that the acute lower respiratory infections (alri) are associated with a newly discovered virus, human metapneumovirus (hmpv), has been shown in several studies. the authors conducted this study to understand the etiological and clinical characteristics of bronchiolitis, one of the most common alri in infants, caused by hmpv.200415189701
the impact of respiratory syncytial virus infection on endothelin receptor function and release in sheep bronchial explants.we investigated the impact of respiratory syncytial virus (rsv) infection, an important asthma precipitant, on endothelin receptor function and release in sheep bronchial explants. rsv infection was confirmed using polymerase chain reaction and immunohistochemistry. since sheep airway smooth muscle contains only endothelin-a receptors, sarafotoxin (stx) s6c did not cause airway contraction. in contrast, sarafotoxin s6c (300 nm) caused contraction in rsv-infected bronchial explants (8 +/- 3% carb ...200415838280
immune and functional role of nitric oxide in a mouse model of respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection of respiratory epithelial cell cultures increases expression of inducible nitric oxide synthase (inos). the present study was designed to evaluate both the effect of rsv infection on expression of inos and the role of no in the host responses to rsv infection in vivo.200415633098
inhibition of respiratory syncytial virus infection with intranasal sirna nanoparticles targeting the viral ns1 gene.respiratory syncytial virus (rsv) infection is one of the major causes of respiratory tract infection for which no vaccine or antiviral treatment is available. the rsv ns1 protein seems to antagonize the host interferon (ifn) response; however, its mechanism is unknown. here, we used a plasmid-borne small interfering rna targeting the ns1 gene (sins1) to examine the role of ns1 in modulating rsv infection. rsv replication was reduced in a549 cells, but not ifn-deficient vero cells, transfected w ...200415619625
inhibition of respiratory viruses by nasally administered sirna.respiratory syncytial virus (rsv) and parainfluenza virus (piv) are two respiratory pathogens of paramount medical significance that exert high mortality. at present, there is no reliable vaccine or antiviral drug against either virus. using an rna interference (rnai) approach, we show that individual as well as joint infection by rsv and piv can be specifically prevented and inhibited by short interfering rnas (sirnas), instilled intranasally in the mouse, with or without transfection reagents. ...200415619632
severe respiratory syncytial virus bronchiolitis: epidemiologic variations associated with the initiation of palivizumab in severely premature infants with bronchopulmonary dysplasia.the efficacy of palivizumab prophylaxis after bronchopulmonary dysplasia (bpd) has been demonstrated in a single placebo-controlled trial. concern has emerged about the degree of efficacy of palivizumab. this study was designed to determine the efficacy of administration of palivizumab to premature infants with a gestational age </=32 weeks, a past history of bpd and younger than 6 months of age at the start of the epidemic.200415626942
administration of the first dose of palivizumab immunoprophylaxis against respiratory syncytial virus in infants before hospital discharge: what is the evidence for its benefit?palivizumab is 1 of 2 agents used to prevent severe lower respiratory tract disease due to respiratory syncytial virus (rsv) infection. the american academy of pediatrics and the american college of obstetricians and gynecologists recommend administering the first dose of rsv immunoprophylaxis to eligible infants before hospital discharge. unfortunately, third-party payers frequently do not separately reimburse administration of this therapy to hospitalized infants.200415823776
gene delivery into the chicken embryo by using replication-competent retroviral vectors.rous sarcoma virus (rsv)-derived retroviral vectors have allowed for efficient gene transfer into the chicken embryo which is a classical model for studying vertebrate development. current evidence reveals that this method can be used for regionally restricted expression, inducible expression, and for interfering with endogenous gene function, suggesting that gain-of-function and loss-of-function strategies for specific genes can be achieved spatially and temporally in the avian embryo. thus, re ...200415779569
evaluation of binax now rsv as an acute point-of-care screening test in a paediatric accident and emergency unit.point-of-care tests (pocts) for respiratory syncytial virus infections are a useful adjunct to reduce the risk of healthcare-associated infections in paediatric wards. a new test based on immunochromatography, binax now rsv, was introduced in the winter of 2002-03. it has user friendly features making it particularly suitable for non-laboratory personnel in a paediatric accident and emergency unit. a prospective study comparing the poct with laboratory-based direct immunofluorescence (dif) showe ...200415779800
severe respiratory syncytial virus bronchiolitis in children: from short mechanical ventilation to extracorporeal membrane oxygenation.the objective of this study was to describe the characteristics of children who required mechanical ventilation (mv) or extracorporeal membrane oxygenation (ecmo) support for respiratory syncytial virus (rsv) bronchiolitis, and to identify risk factors associated with disease severity assessed by duration of mv, mortality and need for ecmo. ventilated children under 1 year of age admitted for bronchiolitis were retrospectively studied over the 8-year period 1996-2003. the study population includ ...200415703980
respiratory viruses in the pediatric intensive care unit: prevalence and clinical aspects.a survey was conducted in two pediatric intensive care units in hospitals in porto alegre, brazil, in order to monitor the main respiratory viruses present in bronchiolitis and/or pneumonia and their involvement in the severity of viral respiratory infections. viral respiratory infection prevalence was 38.7%. in bronchiolitis, respiratory syncytial virus (rsv) was detected in 36% of the cases. in pneumonia, the prevalence rates were similar for adenovirus (10.3%) and rsv (7.7%). there was a diff ...200415761607
respiratory syncytial virus infection: denominator-based studies in indonesia, mozambique, nigeria and south africa.to assess the burden of respiratory syncytial virus (rsv)-associated lower respiratory infections (lri) in children in four developing countries.200415654405
respiratory syncytial virus activity--united states, 2003-2004.respiratory syncytial virus (rsv) is a major cause of lower respiratory tract infections (lrtis) (i.e., bronchiolitis and pneumonia) among young children, resulting in an estimated 51,000-82,000 hospitalizations annually. rsv causes severe disease among older adults and persons of all ages with compromised respiratory, cardiac, or immune systems, and can exacerbate chronic cardiac and pulmonary conditions. in temperate climates, rsv infections occur primarily during annual winter season outbreak ...200415614230
hospitalisations for respiratory syncytial virus bronchiolitis in akershus, norway, 1993-2000: a population-based retrospective study.rsv is recognized as the most important cause of serious lower respiratory tract illness in infants and young children worldwide leading to hospitalisation in a great number of cases, especially in certain high-risk groups. the aims of the present study were to identify risk groups, outcome and incidences of hospitalisation for rsv bronchiolitis in norwegian children under two years of age and to compare the results with other studies.200415606912
alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection.the mechanisms by which respiratory syncytial virus (rsv) infection causes airway hyperresponsiveness (ahr) are not fully established. we hypothesized that rsv infection may alter the expression of airway sensory neuropeptides, thereby contributing to the development of altered airway function. balb/c mice were infected with rsv followed by assessment of airway function, inflammation, and sensory neuropeptide expression. after rsv infection, mice developed significant airway inflammation associa ...200415608150
palivizumab: new indication. moderate reduction in hospitalisation rate.(1) respiratory syncytial virus (rsv) infection is common in infants; it is usually mild except in high risk children. (2) palivizumab, a monoclonal antibody against rsv, was the first preventive treatment to be marketed in france. the licence was recently extended in france to cover children under 2 years of age who have haemodynamically significant congenital heart disease. (3) follow-up data from spanish cohorts of premature infants and infants with bronchopulmonary dysplasia are now availabl ...200415612142
drugs for the management of respiratory syncytial virus infection.the management of infants hospitalized with respiratory syncytial virus infection is essentially supportive. drug therapy can have benefits, but these may only be short-term. systematic review of randomized trials has demonstrated that bronchodilator administration only significantly improves clinical scores. neither corticosteroids nor ribavirin influence the course of the acute illness, and whether they reduce the associated chronic respiratory morbidity remains controversial. preliminary resu ...200415600242
pertussis vaccination and the risk of respiratory syncytial virus-associated hospitalization.animal data suggest an association between recent vaccination with a pertussis-containing vaccine and increased severity of respiratory syncytial virus (rsv) infection. we sought to determine whether such an association exists in humans by studying a population-based cohort of young children.200415602187
practical implementation of a multiplex pcr for acute respiratory tract infections in children.molecular testing for acute respiratory infections (aris) has documented value but limited implementation due to questions that typically slow the acceptance of new tests. this study sought to address these questions and achieve implementation. rhinovirus was added to a nested multiplex pcr (m-pcr), increasing its diagnostic yield. over one winter, three hospital pediatric departments used the m-pcr to complement their direct fluorescent-antibody assay (dfa) for respiratory syncytial virus (rsv) ...200415583287
a review of the effects of breastfeeding on respiratory infections, atopy, and childhood asthma.the etiology of childhood asthma is not fully understood. early exposure to certain respiratory infections may be protective for atopy and/or asthma whereas some infections have been suggested to exert the opposite effects. wheezing lower respiratory illness (lri) in the first year of life and atopy are independently associated with increased risk for current asthma in childhood and their effects are mediated via different causal pathways. these risk factors are multiplicative when they operate ...200415584310
specific inhibition of type i interferon signal transduction by respiratory syncytial virus.respiratory viruses often express mechanisms to resist host antiviral systems, but the biochemical basis for evasion of interferon effects by respiratory syncytial virus (rsv) is poorly defined. in this study, we identified rsv effects on interferon (ifn)-dependent signal transduction and gene expression in human airway epithelial cells. initial experiments demonstrated inhibition of antiviral gene expression induced by ifn-alpha and ifn-beta, but not ifn-gamma, in epithelial cells infected with ...200414722224
respiratory syncytial virus deficient in soluble g protein induced an increased proinflammatory response in human lung epithelial cells.respiratory syncytial virus (rsv) is worldwide the single most important respiratory pathogen in infancy and early childhood. the g glycoprotein of rsv, named attachment protein, is produced by rsv-infected lung epithelial cells in both a membrane-anchored (mg protein) and a soluble form (sg protein) that is secreted by the epithelial cell. currently, the biological role of the sg protein in primary rsv infection is still elusive. therefore, we analyzed the inflammatory response of human lung ep ...200415567433
relationship between respiratory syncytial virus infection and acute otitis media in children.respiratory syncytial virus (rsv) is among the major causes of respiratory tract infection in infants and young children, and concomitant acute otitis media (aom) often develops. however, there are only a few reports about aom associated with rsv infection.200415571905
economic analysis of palivizumab in infants with congenital heart disease.palivizumab has been shown to reduce the number of respiratory syncytial virus (rsv)-related hospitalizations by 45% in children with congenital heart disease (chd). the american academy of pediatrics has recommended that infants with hemodynamically significant chd be considered for palivizumab. however, the economic implications of palivizumab prophylaxis in the chd population have not been evaluated. in the present study, we sought to examine the cost savings and cost utility of rsv prophylax ...200415574622
direct cost analyses of palivizumab treatment in a cohort of at-risk children: evidence from the north carolina medicaid program.use of palivizumab prophylactic therapy reduces the occurrence of hospitalizations for serious respiratory syncytial virus (rsv) lower respiratory tract infections in at-risk infants. the direct cost-benefit of palivizumab prophylaxis for infants who are born at 32 to 35 weeks' estimated gestational age (ega) during their first year of life has not been systematically examined. the objective of this study was to compare the direct costs of palivizumab prophylaxis and rsv treatment in infants who ...200415574623
identifying risk factors for severe respiratory syncytial virus among infants born after 33 through 35 completed weeks of gestation: different methodologies yield consistent findings.prematurity is a proven risk factor for severe respiratory syncytial virus (rsv) infection. prematurity leads to an increased need for, and duration of, hospital admission, intensive care, mechanical ventilation and supplemental oxygen, as well as increased mortality.200415577573
the changing epidemiology of respiratory syncytial virus and influenza: impetus for new control measures.influenza and respiratory syncytial virus (rsv) are the most important causes of medically attended acute respiratory illnesses. medical encounters for acute respiratory illness peak each winter, coinciding with the peak of influenza activity. rsv is the most important cause of hospitalization of infants for acute lower respiratory illness.200415577574
animal models for studying respiratory syncytial virus infection and its long term effects on lung function.human respiratory syncytial virus (hrsv) infection causes a spectrum of illnesses ranging from mild infection to life-threatening bronchiolitis and respiratory failure. human studies on the pathogenesis of rsv infection are invaluable, but animal models permit advances with the use of experimental strategies that would be inappropriate in human studies.200415577578
immunization against viral respiratory disease: a review.healthy and at risk children are susceptible to the morbidity and mortality associated with viral-induced respiratory diseases, including respiratory syncytial virus (rsv) and influenza. the world health organization is attempting to develop and distribute effective vaccines to prevent/reduce key viral respiratory diseases.200415577581
risk of bacterial infection in previously healthy respiratory syncytial virus-infected young children admitted to the intensive care unit.to evaluate the risk of bacterial infection and use of antibiotics in otherwise healthy children infected with respiratory syncytial virus (rsv) admitted to the intensive care unit (icu).200415545852
rhinovirus-associated wheezing in infancy: comparison with respiratory syncytial virus bronchiolitis.there is increasing evidence that rhinoviruses (rv) are able to cause lower airway infections and to induce wheezing in young children. there are few data on the clinical characteristics of rv infections in infants.200415545853
evaluation of combined live, attenuated respiratory syncytial virus and parainfluenza 3 virus vaccines in infants and young children.we evaluated a combination respiratory syncytial virus (rsv) and parainfluenza 3 virus (piv3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6-18 months old. rsv cpts-248/404 and piv3-cp45 vaccines were combined in a dose of 10(5) plaque-forming units of each per 0.5-ml dose and compared with monovalent vaccines or placebo. the virus shedding pattern of rsv was not different between monovalent rsv cpts-248/404 vaccine and com ...200415551207
[etiological study on an outbreak of acute respiratory infection in children in beijing].an outbreak of acute respiratory infections in children occurred in beijing from november to december, 2002. to investigate the etiological agents of affected children who were in day care centers and primary schools.200415555388
reduced clearance of respiratory syncytial virus infection in a preterm lamb model.respiratory syncytial virus (rsv) causes significant respiratory disease in children worldwide. for the study of severe rsv disease seen in preterm infants, a suitable animal model is lacking. the novel hypothesis of this study was that preterm lambs are susceptible to bovine rsv (brsv) infection, an analogous pneumovirus with ruminant host specificity, and that there would be age-dependent differences in select rsv disease parameters. during rsv infection, preterm lambs had elevated temperature ...200415555538
thermostability of the human respiratory syncytial virus fusion protein before and after activation: implications for the membrane-fusion mechanism.anchorless fusion (f) proteins () of human respiratory syncytial virus (rsv) are seen by electron microscopy as unaggregated cones when the proteolytic cleavage at two furin sites required for membrane-fusion activity is incomplete, but aggregate into rosettes of lollipop-shaped spikes following cleavage. to show that this aggregation occurred by interactions of the fusion peptide, a deletion mutant of lacking the first half of the fusion peptide was generated. this mutant remained unaggregated ...200415557241
biochemical prevention and treatment of viral infections - a new paradigm in medicine for infectious diseases.for two centuries, vaccination has been the dominating approach to develop prophylaxis against viral infections through immunological prevention. however, vaccines are not always possible to make, are ineffective for many viral infections, and also carry certain risk for a small, yet significant portion of the population. in the recent years, fda's approval and subsequent market acceptance of synagis, a monoclonal antibody indicated for prevention and treatment of respiratory syncytial virus (rs ...200415560846
protein kinase c-alpha activity is required for respiratory syncytial virus fusion to human bronchial epithelial cells.respiratory syncytial virus (rsv) infection activates protein kinase c (pkc), but the precise pkc isoform(s) involved and its role(s) remain to be elucidated. on the basis of the activation kinetics of different signaling pathways and the effect of various pkc inhibitors, it was reasoned that pkc activation is important in the early stages of rsv infection, especially rsv fusion and/or replication. herein, the role of pkc-alpha during the early stages of rsv infection in normal human bronchial e ...200415564481
role of nedd4 and ubiquitination of rous sarcoma virus gag in budding of virus-like particles from cells.rous sarcoma virus (rsv) budding requires an interaction of the l domain within the p2b region of gag with cellular nedd4-family e3 ubiquitin protein ligases. members of our laboratories previously demonstrated that overexpression of a fragment of the chicken nedd4-like protein (ldi-1 ww) inhibits gag release in a dominant-negative manner (a. kikonyogo, f. bouamr, m. l. vana, y. xiang, a. aiyar, c. carter, and j. leis, proc. natl. acad. sci. usa 98:11199-11204, 2001). we have now identified the ...200415564502
prospective evaluation of a dot-blot enzyme immunoassay (directigen rsv) for the antigenic detection of respiratory syncytial virus from nasopharyngeal aspirates of paediatric patients.this study investigated the efficacy of a commercial enzyme immunoassay (directigen rsv, colorpac) in comparison with the shell vial culture method (using hep-2 cells) for the detection of respiratory syncytial virus (rsv) in nasopharyngeal aspirates from children with bronchiolitis. during the period 1995-2002, 4950 samples were examined. rsv was detected in 1660 (33.5%) samples, with a sensitivity of 80.9%, a specificity of 97.5%, a positive predictive value of 93.8%, a negative predictive val ...200415521998
respiratory syncytial virus and other pneumoviruses: a review of the international symposium--rsv 2003.the respiratory syncytial virus 2003 symposium took place from 8th-11th november 2003 in stone mountain, georgia, and brought together more than 200 international investigators engaged in rsv research. rsv biology, pathogenesis, and clinical data, as well as rsv vaccines and antivirals, were addressed in the meeting, and this review will aim to briefly summarize and discuss the implications of new findings. the meeting also served as the inauguration of the robert m. chanock award for lifetime a ...200415522442
[the anti-respiratory syncytial virus (rsv) effect of radix glycyrrhizae in vitro].to develop safe and effective anti-rsv new medicine from radix glycyrrhizae.200415524297
evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis.the interaction between the respiratory syncytial virus (rsv) polymerase complex and lipid rafts was examined in hep2 cells. lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by western blotting and mass spectrometry. this analysis revealed the presence of the n, p, l, m2-1 and m proteins. however, these proteins appeared to differ from one another in their association with these structures, with the m2-1 protein showing a greater partitioning in ...200415527841
replication-dependent potent ifn-alpha induction in human plasmacytoid dendritic cells by a single-stranded rna virus.plasmacytoid dendritic cells sense viral ssrna or its degradation products via tlr7/8 and cpg motifs within viral dna via tlr9. although these two endosomal pathways operate independently of viral replication, little is known about the detection of actively replicating viruses in plasmacytoid dendritic cell (pdc). replication and transcription of the viral genome of ssrna viruses as well as many dna viruses lead to the formation of cytosolic dsrna absent in noninfected cells. in this study, we u ...200415528327
anti-g protein antibody responses to respiratory syncytial virus infection or vaccination are associated with inhibition of g protein cx3c-cx3cr1 binding and leukocyte chemotaxis.respiratory syncytial virus (rsv) is an important cause of severe lower respiratory tract illness in infants and the elderly. presently, no safe and efficacious rsv vaccine exists; however, advances in our understanding of immunity and the pathogenesis of disease associated with rsv infection may lead to new vaccine strategies. rsv g protein contains a cx3c chemokine motif that interacts with the cx3cr1 chemokine receptor and modifies the activities of fractalkine. in the present study, we show ...200415529257
variable resistance to palivizumab in cotton rats by respiratory syncytial virus mutants.palivizumab (pz) is the only monoclonal antibody in use against a human infectious disease. pz is given as prophylaxis against infection with respiratory syncytial virus (rsv). an rsv escape mutant, mp4, has been shown to resist pz prophylaxis in cotton rats.200415529258
protective and disease-enhancing immune responses induced by recombinant modified vaccinia ankara (mva) expressing respiratory syncytial virus proteins.modified vaccinia ankara (mva) recombinants expressing single or multiple rsv surface proteins (f or g) are promising potential vaccines. we studied humoral and cellular responses induced by mva-f and mva-g in mice, comparing them to a formalin inactivated rsv preparation (fi-rsv) known to increase disease severity. mva-f or mva-g vaccination enhanced weight loss during rsv challenge, but did not show the lung eosinophilia seen after fi-rsv vaccination. fi-rsv induced a stronger total rsv igg re ...200415531040
do environmental pollutants influence the onset of respiratory syncytial virus epidemics or disease severity?the trigger for annual epidemics of respiratory syncytial virus (rsv) infections and the factors contributing to the disappearance of rsv infections in late winter remain obscure. similarly, there is no adequate explanation for the higher morbidity and admission rates in industrialised as compared with rural areas. it has been suggested that a variety of environmental factors such as temperature, daylight and humidity may influence the onset and waning of the epidemics. however, the few studies ...200415531259
the neuroendocrine stress response and severity of acute respiratory syncytial virus bronchiolitis in infancy.neuroendocrine hormones have profound effects on the immune system. the immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (rsv) infection. we hypothesised that there is a relationship between the neuroendocrine response in acute rsv infection, the severity of illness, and the degree of lymphopenia.200415536526
[use of palivizumab for the prevention of respiratory syncytial virus infections in children with congenital heart disease. recommendations from the french paediatric cardiac society].palivizumab is now authorized in france for prophylaxis of respiratory syncytial virus (rsv) infections in infants with haemodynamically significant congenital cardiac disease. a multicentre randomised trial was shown that treatment was safe and effective for such children. the therapeutic protocol is similar to that used in preterm infants and consists of five, monthly, intramuscular injections of palivizumab, at a dose of 15 mg/kg, started 2 months before the onset of epidemic season. to guide ...200415519844
identification of a common hla-dp4-restricted t-cell epitope in the conserved region of the respiratory syncytial virus g protein.the cellular immune response to respiratory syncytial virus (rsv) is important in both protection and immunopathogenesis. in contrast to hla class i, hla class ii-restricted rsv-specific t-cell epitopes have not been identified. here, we describe the generation and characterization of two human rsv-specific cd4(+)-t-cell clones (tccs) associated with type 0-like cytokine profiles. tcc 1 was specific for the matrix protein and restricted over hla-dpb1*1601, while tcc 2 was specific for the attach ...200414747542
variables explaining the duration of hospitalization in children under two years of age admitted with acute airway infections: does respiratory syncytial virus have a direct impact?duration of hospitalization is influenced by many factors. it is an important parameter for quality of care. so far it is unknown, whether respiratory syncytial virus (rsv) etiology itself contributes to the time in hospital.200414747964
orally active fusion inhibitor of respiratory syncytial virus.bms-433771 was found to be a potent inhibitor of respiratory syncytial virus (rsv) replication in vitro. it exhibited excellent potency against multiple laboratory and clinical isolates of both group a and b viruses, with an average 50% effective concentration of 20 nm. mechanism-of-action studies demonstrated that bms-433771 inhibits the fusion of lipid membranes during both the early virus entry stage and late-stage syncytium formation. after isolation of resistant viruses, resistance was mapp ...200414742189
sphingosine kinase mediates activation of extracellular signal-related kinase and akt by respiratory syncytial virus.respiratory syncytial virus (rsv) preferentially infects lung epithelial cells. infected cells remain viable well into the infection. this prolonged survival results from rsv-induced activation of pro-survival pathways, including akt and extracellular signal-related kinase (erk). sphingosine 1-phosphate (s1p) is a sphingolipid metabolite with demonstrated links to cell survival. it is enzymatically generated by sequential activation of ceramidase (generation of sphingosine) and sphingosine kinas ...200414742298
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