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persistence of respiratory syncytial virus in macrophages alters phagocytosis and pro-inflammatory cytokine production.functions of macrophage are known to be altered by acute infection with respiratory syncytial virus (rsv). however, it is unknown whether the persistent presence and expression of the rsv genome have any effect on the functions of these cells. we used a murine macrophage-like cell line (p388d1) persistently infected with rsv to determine: (i) phagocytic activity mediated by fcgamma receptors, (ii) expression of fcgamma receptors, and (iii) production of il-1beta, il-6 and tnf-alpha. viral persis ...200111270594
identification and characterisation of multiple linear b cell protectopes in the respiratory syncytial virus g protein.respiratory syncytial virus (rsv) is an important respiratory pathogen in man, against which no vaccine is available. however, recent evidence suggests that antibodies to the rsv f and g proteins may play an important role in disease prevention. we previously demonstrated that bbg2na, a subunit vaccine candidate including residues 130-230 of the long strain g protein, protects rodents against rsv challenge. using a panel of monoclonal antibodies (mab) and synthetic peptides, five linear b cell e ...200111257359
membrane-associated respiratory syncytial virus f protein expressed from a human rhinovirus type 14 vector is immunogenic.human rhinovirus (hrv) replicons have the potential to serve as respiratory vaccine vectors for mucosal immunization in humans. however, since many vaccine immunogens of interest are glycosylated, an important concern is whether hrv replicons are capable of expressing glycosylated proteins. the human respiratory syncytial virus (rsv) fusion (f) protein was chosen as a model glycoprotein and the hrv replicon deltap1fvp3 was generated by inserting the f protein-coding sequence in frame and in lieu ...200111277694
pathogenesis of rsv lower respiratory tract infection: implications for vaccine development.respiratory syncytial virus (rsv) infection is the most prevalent cause of severe respiratory disease in infants. it also causes considerable morbidity in older children and adults with underlying risk factors. rsv vaccine development has been complicated by the need to administer the vaccine at a very young age and by enhanced disease observed after vaccination with formalin inactivated rsv. for infants live attenuated vaccines, which may not be expected to predispose for vaccine induced enhanc ...200111282187
inhibition of t1/st2 during respiratory syncytial virus infection prevents t helper cell type 2 (th2)- but not th1-driven immunopathology.t cells secreting interleukin (il)-4 and il-5 (t helper cell type 2 [th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. t1/st2 is a surface ligand of the il-1 receptor family, expressed on th2- but not on interferon (ifn)-gamma-producing th1 cells. prior exposure of balb/c mice to the attachment (g) or fusion (f) protein of respiratory syncytial virus (rsv) increases illness severity during intranasal rsv challenge, due ...200111283151
respiratory syncytial virus groups a and b in porto alegre, brazil, from 1990 to 1995 and 1998.we analyzed the respiratory syncytial virus (rsv) groups and their epidemiological pattern that were detected over the course of seven years in southern brazil. the two rsv groups co-circulated each year, but frequencies of groups a and b varied both between and within yearly outbreaks. in 1991, group a predominated over group b (p=0.0016). rsv outbreaks analyzed showed a temperature-dependent pattern and no association with rainfall, similarly to other countries from southern south america. kno ...200111285489
oxidant tone regulates rantes gene expression in airway epithelial cells infected with respiratory syncytial virus. role in viral-induced interferon regulatory factor activation.respiratory syncytial virus (rsv) produces intense pulmonary inflammation, in part, through its ability to induce chemokine synthesis in infected airway epithelial cells. rantes (regulated upon activation, normal t-cells expressed and secreted) is a cc chemokine which recruits and activates monocytes, lymphocytes, and eosinophils, all cell types present in the lung inflammatory infiltrate induced by rsv infection. in this study we investigated the role of reactive oxygen species in the induction ...200111259439
2001 aspet otto krayer award lecture. molecular targets for antiviral agents.there are a number of virus-specific processes within the virus replicative cycle or virus-infected cell that have proven to be attractive targets for chemotherapeutic intervention, i.e., virus adsorption and entry into the cells, reverse (rna --> dna) transcription, viral dna polymerization, and cellular enzymatic reactions that are associated with viral dna and rna synthesis and viral mrna maturation (i.e., methylation). a variety of chemotherapeutic agents, both nucleoside (and nucleotide) an ...200111259521
validation of synthetic peptide enzyme immunoassays in differentiating two subgroups of ruminant respiratory syncytial virus.subgroup-specific peptide-based enzyme immunoassays from each respective g-glycoprotein of the ovine and the bovine respiratory syncytial virus (rsv) were developed to detect rsv-specific igg responses in cattle. antigenic peptides from the respective g-glycoprotein were identified from the extracellular central hydrophobic region (amino acids 158-189) located between 2 mucin-rich regions. these antigenic peptides identified by epitope mapping from each g-glycoprotein were synthesized and used t ...200111289207
prevalence of ovine and bovine respiratory syncytial virus infections in cattle determined with a synthetic peptide-based immunoassay.subgroup-specific peptide-based enzyme-linked immunosorbent assays from the g-protein of the ovine and bovine respiratory syncytial virus (rsv), respectively, were used to determine the prevalence of the ovine and bovine subgroup strains of rsv infections in cattle. a total of 1,102 bovine serum samples were obtained from 6 diagnostic laboratories located in the northwestern and the southeastern usa and were tested for antibody to either the bovine or ovine subgroups of rsv. antibody to viruses ...200111289208
self-replicative rna vaccines elicit protection against influenza a virus, respiratory syncytial virus, and a tickborne encephalitis virus.in genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually dna. this study addressed the possibility of using the recombinant alpha virus rna molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. mice were immunized with recombinant semliki forest virus rna-encoding envelope proteins from one of 3 viruses: influenza a virus, a tickborne flavivirus (louping ill virus), or respiratory syncytial virus (rsv). ...200111294672
airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing.respiratory syncytial virus (rsv) lower respiratory tract infection (lrti) is frequently followed by recurrent wheezing. thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to rsv lrti.200111303830
a comparison of cytokine responses in respiratory syncytial virus and influenza a infections in infants.respiratory syncytial virus (rsv) infection is a major cause of bronchiolitis in infants while influenza a infection usually manifests as upper respiratory tract infection. we hypothesised that the immunological responses of infants to rsv infection and influenza a infection are different. this prospective study was undertaken to compare the cytokine responses during rsv and influenza a infection. sera and nasopharyngeal aspirates (npa) were collected from infants with a coryzal illness with or ...200111271383
recombinant bovine/human parainfluenza virus type 3 (b/hpiv3) expressing the respiratory syncytial virus (rsv) g and f proteins can be used to achieve simultaneous mucosal immunization against rsv and hpiv3.recombinant bovine/human parainfluenza virus type 3 (rb/hpiv3), a recombinant bovine piv3 (rbpiv3) in which the f and hn genes were replaced with their hpiv3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (rsv) in order to create a bivalent mucosal vaccine against rsv and hpiv3. the attenuation of rb/hpiv3 is provided by the host range restriction of the bpiv3 backbone in primates. rsv g and f open reading frames (orfs) were placed under the contro ...200111312329
importance of the n terminus of rous sarcoma virus protease for structure and enzymatic function.all retrovirus proteases (prs) are homodimers, and dimerization is essential for enzymatic function. the dimer is held together largely by a short four-stranded antiparallel beta sheet composed of the four or five n-terminal amino acid residues and a similar stretch of residues from the c terminus. we have found that the enzymatic and structural properties of rous sarcoma virus (rsv) pr are exquisitely sensitive to mutations at the n terminus. deletion of one or three residues, addition of one r ...200111312348
chimeric subgroup a respiratory syncytial virus with the glycoproteins substituted by those of subgroup b and rsv without the m2-2 gene are attenuated in african green monkeys.using the existing reverse genetics system developed for the subgroup a respiratory syncytial virus (rsv), a chimeric virus (designated ra-g(b)f(b)) that expresses subgroup b-specific antigens was constructed by replacing the g and f genes of the a2 strain with those of the 9320 strain of subgroup b rsv. ra-g(b)f(b) grew well in tissue culture, but it was attenuated in the respiratory tracts of cotton rats and african green monkeys. to further attenuate this chimeric rsv, the m2-2 open reading f ...200111312662
predictors of a normal chest x-ray in respiratory syncytial virus infection.respiratory syncytial virus (rsv) accounts for the majority of lower respiratory tract infections (lrti) in infants and young children. a chest x-ray is frequently performed in infants with lrti caused by rsv. the aim of this study was to develop and validate a prediction model to estimate the probability for a normal chest x-ray in children with rsv infection. for this purpose, easy obtainable diagnostic parameters were used. this prediction model may be applied to decide which patients do not ...200111288209
evaluation of the hexaplex assay for detection of respiratory viruses in children.the hexaplex assay (prodesse, inc., milwaukee, wis.) is a multiplex reverse transcriptase (rt)-pcr assay for the detection of parainfluenza virus types 1, 2, and 3, respiratory syncytial virus (rsv) types a and b, and influenza virus types a and b. we evaluated the hexaplex assay in comparison with conventional viral cell cultures and rapid enzyme immunoassays (eias) for rsv (directigen; becton dickinson inc., cockeysville, md.) and influenza a virus (abbott test pack; abbott laboratories, abbot ...200111325976
the discovery of rfi-641 as a potent and selective inhibitor of the respiratory syncytial virus.the design and synthesis of a new potent and selective inhibitor of the respiratory syncytial virus are described. this compound, rfi-641, emerged from analysis of the structure-activity relationship in a series of biphenyl triazine anionic compounds possessing specific anti-rsv activity. the key synthetic step involves coupling of diaminobiphenyl 11 with two equivalents of chlorotriazine 10 under microwave conditions. rfi-641 inhibited rsv in vitro and in vivo models.200111327584
leucocyte populations in respiratory syncytial virus-induced bronchiolitis.to enumerate the cellular composition of the airways in infants with acute bronchiolitis.200111328469
in vitro inactivation of chlamydia trachomatis and of a panel of dna (hsv-2, cmv, adenovirus, bk virus) and rna (rsv, enterovirus) viruses by the spermicide benzalkonium chloride. 200111328797
inhalation of corticosteroids after hospital care for respiratory syncytial virus infection diminishes development of asthma in infants.the aim of the study was to assess the effect of inhaled corticosteroids on subsequent respiratory symptoms and asthma in infants hospitalized for respiratory syncytial virus infection (rsv). the study included 188 children below 12 mo of age, hospitalized because of rsv infection. during the winter of 1994/95 only selected children (13%) were given inhaled corticosteroids following discharge from the hospital. the following winter (1995/96), almost all children (86%) were given this treatment f ...200111332164
recent advances in the management and prophylaxis of respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is an important cause of morbidity, particularly in prematurely born infants who have had chronic lung disease. current therapy is essentially supportive. overall, the results of randomized trials do not support the use of bronchodilators, corticosteroids or ribavirin. nitric oxide and exogenous surfactant may improve the respiratory status of those infants who require ventilatory support. nosocomial infection can be reduced by appropriate handwashing. ...200111332948
benefits of thickened feeds in previously healthy infants with respiratory syncytial viral bronchiolitis.infants with respiratory syncytial virus (rsv) bronchiolitis have an increased risk of aspiration. the optimal feeding strategy for these patients has not been described. fifteen previously healthy and clinically stable infants with rsv bronchiolitis underwent video-fluoroscopy studies to assess swallowing using thin barium. those with abnormal studies underwent a repeat study, using barium that was thickened with rice cereal. nine of 15 infants had abnormal studies with thin barium. laryngeal o ...200111288213
[respiratory syncytial virus infection in high-risk infants].the authors describes the frequency of respiratory syncytial virus (rsv) infections in high risk infants in ten hospitals, between 01.02.1999.-15.03.1999. rsv antigen test were performed from the nasopharyngeal or throat swabs of 58 infants with respiratory tract infections. thirteen patients were positive. among them 11 were prematures. six infants were still receiving treatment in neonatal intensive care unit, while seven infants were readmitted to a pediatric intensive care unit. distribution ...200111305233
immunoregulatory role of secreted glycoprotein g from respiratory syncytial virus.the secretory glycoprotein (gs) of respiratory syncytial virus (rsv) was enriched and investigated for its effects on t cells specific for rsv and unrelated antigens. gs exhibited a dose dependent suppression of lymphoproliferative responses in peripheral blood mononuclear cells (pbmcs), specific for mycobacterial lysates or tetanus toxoid. however, gs did not inhibit live rsv specific t cell responses. these results suggest that gs may suppress immune response to unrelated antigens, but should ...200111325469
allium sativum potentiates suicide gene therapy for murine transitional cell carcinoma.this study evaluated the synergistic effect of allium sativum (as) with suicide gene therapy for transitional cell carcinoma (tcc) of the bladder. subcutaneous tccs were established in syngeneic c3h/he mice with 1 x 10(5) mbt-2 cells. as liquid extract was injected at the site of tumor transplantation on day 1 for three weeks (experiment i) and into the established tumors weekly for five weeks (experiment ii) in combination with or without gene therapy using a replication-defective adenoviral ve ...200011341051
characterization of heterokaryons between skeletal myoblasts and somatic cells formed by fusion with hvj (sendai virus); effects on myogenic differentiation.in skeletal myogenic differentiation, myoblasts fuse with myogenic cells spontaneously, but do not fuse with non-myogenic cells either in vivo or in vitro, suggesting that the fusion of myoblasts with non-myogenic cells is unsuitable for differentiation. to understand the inevitability of the fusion among myoblasts, we prepared heterokaryons in crosses between quail myoblasts transformed with a temperature-sensitive mutant of rous sarcoma virus (qm-rsv cells) and rodent non-myogenic cells, such ...200111345502
[seasonal trends of respiratory syncytial virus infections on réunion island gathering data among hospitalized children].little is known about the epidemiology of respiratory syncytial virus (rsv) infections in tropical countries and in particular in tropical islands of the indian ocean. our study reviewed all cases of rsv infections diagnosed among hospitalized children in the hospital de saint pierre de la réunion, from january 1993 to december 1999. 849 cases were identified of which 67.7% were infants under 6 months old. most cases occurred from december to may (89% of all cases), showing a significant correla ...200111346979
evaluation of an acute point-of-care system screening for respiratory syncytial virus infection.there continues to be a significant risk of children contracting hospital-acquired infections caused by respiratory syncytial virus (rsv). in order to provide 24 h screening, we examined a point-of-care system (near-patient testing) for use by non-laboratory healthcare workers (hcws) in a short stay unit adjoining the accident and emergency department of a large paediatric hospital. three studies were conducted over consecutive winter epidemics, in which 2193 nasopharyngeal aspirates were obtain ...200111358472
rhoa is activated during respiratory syncytial virus infection.respiratory syncytial virus (rsv) is an important human pathogen that can cause severe and life-threatening respiratory infections in infants and immunocompromised adults. we have recently shown the rsv f glycoprotein, which mediates viral fusion and entry, interacts with the cellular protein rhoa in two-hybrid and in vitro binding assays. whether this interaction occurs in living cells remains an open question. however, because rhoa signaling is associated with many cellular functions relevant ...200111336544
molecular detection of respiratory syncytial virus in postmortem lung tissue samples from mexican children deceased with pneumonia.respiratory syncytial virus (rsv) is the major viral cause of severe respiratory infections in children younger than 2 years of age. nevertheless there are not enough epidemiologic data about the role of rsv as a cause of infantile mortality from pneumonia, mainly in young children from developing countries aim. to determine the frequency of rsv infection in lung tissue samples from mexican children deceased with pneumonia, by reverse transcription (rt) and pcr.200111368106
[analysis of etiology of influenza-like morbidity and monitoring influenza epidemic of 1998-1999 by laboratory diagnosis methods].the etiological structure of influenza-like was analyzed in the population in cities and towns and in russia as a whole in november 1998 to april 1999 by the findings of immunofluorescence and serological surveys of patients with acute respiratory viral infections (arvi). by the results of both tests, the proportion of the incidence of influenza a (h3n2) was largest, the decreasing order in their significance was as follows: adenoviruses, type 3 parainfluenza virus, rsv, influenza b virus, influ ...200111338361
genetic variability of respiratory syncytial virus subgroup b strain isolated during the last 20 years from the same region in japan: existence of time-dependent linear genetic drifts.the genetic variability of 32 respiratory syncytial virus (rsv) sub-group b isolates from a single community in japan during the 20 years from 1980 to 1999 was determined. two variable regions of the attachment (g) protein gene were amplified by reverse transcriptase-polymerase chain reaction amplification and their products were sequenced directly. phylogenetic analysis of nucleotide sequences revealed seven distinct branches in which strains isolated during seasons of close proximity were loca ...200111338383
multicentered study of viral acute lower respiratory infections in children from four cities of argentina, 1993-1994.this study describes the first multicentered study of acute lower respiratory infection viral etiology in young children from four different geographical areas of argentina. a total of 1,278 children under 5 years of age, hospitalized in primary care centers from buenos aires, córdoba, santa fé and mar del plata cities during a 2-year period were studied (1993-1994). nasopharyngeal aspirates were investigated for respiratory syncytial virus (rsv), adenovirus, parainfluenza, and influenza a and b ...200111360249
bronchiolitis in infants.bronchiolitis is a common cause of wheezing among infants. respiratory syncytial virus (rsv) is the most common infectious agent to cause bronchiolitis, and rsv infection accounts for more than 125,000 hospitalizations per year in the united states. beyond supportive measures, the care of infants with bronchiolitis remains controversial. practitioners continue to treat infants with a variety of pharmacologic agents, despite limited evidence of their efficacy. investigators continue to search for ...200111389361
eosinophil cationic protein in infants with respiratory syncytial virus bronchiolitis: predictive value for subsequent development of persistent wheezing.infants with acute bronchiolitis during the first months of life are at increased risk of developing persistent wheezing and bronchial asthma later in life. the study of eosinophil cationic protein (ecp) suggests that eosinophil-related inflammatory mechanisms may play a role in respiratory syncytial virus (rsv) bronchiolitis. the aim of our study was to verify whether serum ecp (s-ecp) measurements are useful in predicting the development of persistent wheezing in children affected by rsv bronc ...200111389573
antiviral activity of an extract derived from roots of eleutherococcus senticosus.a liquid extract from eleutherococcus senticosus roots inhibited the productive replication of human rhinovirus (hrv), respiratory syncytial virus (rsv) and influenza a virus in cell cultures infected with these viruses, all of which belong to the rna type viruses. analysis of virus production after treatment of the infected cells using plaque-reduction assays showed a strong antiviral activity of the eleutherococcus extract. in contrast, no effect was detected using the same protocol for cells ...200111397509
characterization of myogenic cell membrane: spontaneous formation of heterokaryotic myotubes between two different kinds of myoblasts.in a previous study, it has been shown that presumptive mouse c2 myoblast cells are strongly resistant to hvj (hemaglutinating virus of japan, sendai virus)-mediated cell fusion, but do become capable of fusion upon differentiation. quail myoblasts transformed with a temperature-sensitive mutant of rous sarcoma virus (qm-rsv cells) also become more sensitive to hvj-mediated cell fusion during differentiation. investigations were undertaken to see whether heterokaryotic myotubes were formed spont ...200111401331
furin cleavage of the respiratory syncytial virus fusion protein is not a requirement for its transport to the surface of virus-infected cells.the intracellular cleavage of respiratory syncytial virus (rsv) fusion (f) protein by furin was examined. in rsv-infected lovo cells, which express an inactive form of furin, and in rsv-infected vero cells treated with the furin inhibitor decanoyl-arg-val-lys-arg-chloromethyl ketone (dec-rvkr-cmk), the f protein was expressed as a non-cleaved 73 kda species. in both cases the f protein was initially expressed as an endoglycosidase h (endo h)-sensitive precursor (f0(ehs)) which was modified appro ...200111369882
cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (rsv) infection.little is known about inflammatory mediators (im); like cytokines, chemokines and receptors; in respiratory secretion as possible indicators of the severity of respiratory syncytial virus (rsv) disease. nor have systematic studies been published on the ratios between im as such indicators.200111378497
[relationship between respiratory syncytial virus subtype and clinical severity in bronchiolitis].respiratory syncytial virus (rsv) is the most frequently implicated agent in bronchiolitis. the virus presents two antigenic subtypes (a and b). the results of studies on the relationship between viral subtype and clinical severity are conflicting.200111412403
respiratory syncytial virus: update on infection, treatment, and prevention.respiratory syncytial virus (rsv) infection, which primarily manifests as bronchiolitis or pneumonia, is the leading cause of lower respiratory tract infection in infants and young children. it is associated with more than 100,000 pediatric hospitalizations each year in the united states. infants who were premature; have chronic lung disease, congenital heart disease, or immunodeficiency disorders; or have underlying metabolic or neuromuscular disorders are at increased risk for especially sever ...200111384554
respiratory tract infections caused by respiratory syncytial virus in children. diagnosis and treatment.respiratory syncytial virus (rsv) is the most common viral cause of lower respiratory tract infection in infancy and young children. no effective treatment for rsv lower respiratory tract infection (rsv-lrti) exists. ribavirine initially was reported to be an effective anti-viral drug for rsv-lrti. however, subsequently performed trials could not reproduce these positive results and based on the current available evidence there is no place of ribavirin in the routine treatment of rsv-lrti. the u ...200111404731
respiratory syncytial virus immune globulin: decisions and costs.a decision analysis was used to evaluate the economic effectiveness of respiratory syncytial virus immune globulin (rsvig) prophylaxis on selected pediatric populations at risk for developing rsv bronchiolitis or all respiratory illness-related hospitalizations. we compared costs, outcomes, and cost-effectiveness of administering rsvig to no treatment in different pediatric populations, including those at risk of developing rsv-bronchiolitis and those at risk of developing any respiratory illnes ...200111416872
regional impact of prophylaxis with the monoclonal antibody palivizumab on hospitalisations for respiratory syncytial virus in infants.palivizumab is approved in switzerland for prevention of hospitalisation for rsv infection in children with one of the following risk factors: (1) history of prematurity < or = 35 weeks and age < or = 6 months or (2) chronic lung disease and age < or = 1 year. regional data on the expected effectiveness of this monoclonal antibody are not available.200111416887
the constitutive activation of the cef-4/9e3 chemokine gene depends on c/ebpbeta in v-src transformed chicken embryo fibroblasts.the cef-4/9e3 chemokine gene is expressed constitutively in chicken embryo fibroblasts (cef) transformed by the rous sarcoma virus (rsv). this aberrant induction is controlled at the transcriptional and post-transcriptional levels. transcriptional activation depends on multiple elements of the cef-4 promoter composing a src-responsive-unit or sru. the sru includes a tpa responsive element, a prdii/kappab domain and a caat box. in this report, we identify c/ebpbeta as a component of the trans-act ...200111402325
multiple cis regulatory elements control rantes promoter activity in alveolar epithelial cells infected with respiratory syncytial virus.respiratory syncytial virus (rsv) produces intense pulmonary inflammation, in part through its ability to induce chemokine synthesis in infected airway epithelial cells. rantes (regulated upon activation, normally t-cell expressed and presumably secreted) is a cc chemokine which recruits and activates monocytes, lymphocytes, and eosinophils, all cell types present in the lung inflammatory infiltrate induced by rsv infection. in this study, we analyzed the mechanism of rsv-induced rantes promoter ...200111413310
insertion of capsid proteins from nonenveloped viruses into the retroviral budding pathway.retroviral gag proteins direct the assembly and release of virus particles from the plasma membrane. the budding machinery consists of three small domains, the m (membrane-binding), i (interaction), and l (late or "pinching-off") domains. in addition, gag proteins contain sequences that control particle size. for rous sarcoma virus (rsv), the size determinant maps to the capsid (ca)-spacer peptide (sp) sequence, but it functions only when i domains are present to enable particles of normal densi ...200111413320
[use of palivizumab in the prevention of syncytial virus respiratory infection].monthly intramuscular palivizumab (synagis, medimmune, inc.) is effective in reducing the incidence of rsv-attributable hospitalization by 55% if compared with placebo and seems to be well tolerated.200011424809
bbg2na an rsv subunit vaccine candidate intramuscularly injected to human confers protection against viral challenge after nasal immunization in mice.respiratory syncytial virus (rsv) is a major respiratory pathogen responsible for severe pulmonary disease. we have developed a parenterally administered vaccine, bbg2na, which is currently in a phase iii clinical trial. bbg2na comprises residues 130--230 of rsv-a g protein (g2na) fused to the bb carrier protein. in this study, we show that bbg2na can be delivered by the nasal route and generates both mucosal and systemic antibody responses when co-administered with cholera toxin b or a newly de ...200111427280
a novel group iia phospholipase a2 interacts with v-src oncoprotein from rsv-transformed hamster cells.we have isolated a novel isoform of phospholipase a(2). this enzyme was designated srpla(2) because it was discovered while analyzing the proteins interacting with different forms of the v-src oncoproteins isolated from rous sarcoma virus-transformed hamster cells. it contains all the functional regions of the pla(2) group iia proteins but differs at its c-terminal end where there is an additional stretch of 8 amino acids. the srpla(2) isoform was detected as a 17-kda precursor in cells and as a ...200111427522
[respiratory syncytial virus infection and asthma].presentation of bronchial asthma, in the years following the first outbreak of bronchiolitis due to respiratory syncytial virus (rsv) was first described by mcintosh, who postulated a common pathogenesis that was confirmed by the greater frequency (50%) of wheezing bronchiolitis and asthma during the more than 5 year follow up of these children. more recently, hibbert and schroechkenstein have again confirmed this phenomenon. these authors report that the percentage of asthma was increased by up ...200111434889
differential and opposed transcriptional effects of protein fusions containing the vp16 activation domain.overexpression of strong transcriptional activators like herpes simplex virion protein 16 (vp16) may lead to non-specific inhibition of gene expression as a result of the titration of transcription factors. here we report that a fusion between the homeoprotein hoxa2 and the vp16 activation domain inhibits transcription from the strong promoter/enhancers of cytomegalovirus (cmv) and rous sarcoma virus (rsv). a similar fusion involving a hoxa2 mutant protein that is defective in dna binding has no ...200111418119
respiratory syncytial virus infection in the late bone marrow transplant period: report of three cases and review.respiratory syncytial virus (rsv) infection is an important cause of respiratory mortality in immunosuppressed patients, including bone marrow transplant (bmt) recipients. the presence of lower respiratory tract infection and infection in the pre-engraftment phase of bmt is believed to confer a poor prognosis. three patients who underwent allogeneic bmt at our institution developed rsv pneumonia over 1 year post bmt, with the underlying disease in remission. all three were hypoxic with extensive ...200111438823
the use of palivizumab monoclonal antibody to control an outbreak of respiratory syncytial virus infection in a special care baby unit.an outbreak of respiratory syncytial virus (rsv) infection affected seven premature infants in a special care baby unit during november and december 1999. conventional infection control measures (cohorting infected babies, strict reinforcement of the use of gloves and aprons, emphasis on hand disinfection) failed to prevent spread. palivizumab, a respiratory syncytial virus monoclonal antibody, was given to eight high-risk preterm infants. there were no further cases of rsv in the unit and none ...200111439005
management of infections caused by respiratory syncytial virus.this is a consensus document compiled by the medical products agency in sweden and the swedish reference group for antiviral therapy on management of respiratory syncytial virus (rsv) infections. prophylaxis against rsv infections using palivizumab, a commercially available humanized monoclonal igg1 antibody preparation, is recommended for children <2 y of age with chronic respiratory diseases requiring continuous treatment (oxygen and/or inhalations and/or steroids) during the previous 6 months ...200111440215
genetic variability of respiratory syncytial virus subgroup a strain in 15 successive epidemics in one city.the genetic variability of 125 respiratory syncytial virus (rsv) subgroup a isolates over 15 successive epidemics from 1980 to 1995 in an urban population of japan was determined. allocation of isolates into lineages was archived by reverse transcriptase-polymerase chain reaction amplification of selected regions of the nucleoprotein (np) and attachment (g) protein gene followed by restriction fragment length polymorphism (rflp) analysis. three and seven distinct restriction patterns of the np a ...200111424129
phase 1 evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants.intravenous palivizumab (15 mg/kg) was investigated in 2 phase 1 studies among recipients of hematopoietic stem cell transplants (hscts). study 1 included 6 hsct patients without active respiratory syncytial virus (rsv) infection. study 2 included 15 hsct patients with rsv upper respiratory tract infection (urti; n=3) or rsv interstitial pneumonia (ip; n=12), all of whom also received aerosolized ribavirin. peak serum concentrations of palivizumab in the 2 studies were similar. the mean serum ha ...200111443562
local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity.to investigate the role of cell-mediated immunity during respiratory syncytial virus (rsv) infection, interferon (ifn)-gamma and interleukin (il)-10 levels in nasopharyngeal secretions were measured in infants with lower respiratory tract infection (lrti) caused by rsv. a novel technique was used to measure in vivo cytokine levels in nasopharyngeal aspirates (npas). cytokine levels in the npas of 17 mechanically ventilated infants and 43 nonventilated hospitalized infants were compared. as expec ...200111443563
phylogenetic placement of a novel tenuivirus from the grass urochloa plantaginea.evidence is presented that a tenuivirus recovered from the grass urochloa plantaginea is probably a novel tenuivirus species, to be called urochloa hoja blanca virus (uhbv). it is related to both echinochloa hoja blanca virus (ehbv) and rice hoja blanca virus (rhbv), and these three form a group distinct from maize stripe virus (mstv) and rice stripe virus (rstv). phylogenetic analysis of the sequence data for rna-3 and rna-4 of these viruses supports the hypothesis that ehbv and uhbv may have e ...200111450951
rfi-641 inhibits entry of respiratory syncytial virus via interactions with fusion protein.rfi-641, a small dendrimer-like compound, is a potent and selective inhibitor of respiratory syncytial virus (rsv), which is currently a clinical candidate for the treatment of upper and lower respiratory tract infections caused by rsv. rfi-641 inhibits rsv growth with an ic(50) value of 50 nm and prevents syncytia formation in tissue culture. rsv contains of three surface glycoproteins, a small hydrophobic (sh) protein of unknown function, and attachment (g) and fusion (f) proteins that enable ...200111451666
efficacy of recombinant human deoxyribonuclease i in the hospital management of respiratory syncytial virus bronchiolitis.to evaluate the effect of recombinant human deoxyribonuclease i (rhdnase) in shortening the length of the hospitalization and improving the chest radiographs (cxrs) in hospitalized infants with respiratory syncytial virus (rsv) infection as a result of its mucolytic properties.200111451839
a novel bipolar mode of attachment to aluminium-containing adjuvants by bbg2na, a recombinant subunit hrsv vaccine.human respiratory syncytial virus (hrsv) is a major pathogen responsible for bronchiolitis and severe pulmonary disease in very young children, immunodeficient patients and the elderly. bbg2na, a recombinant chimeric protein produced in escherichia coli, is a promising subunit vaccine candidate against this respiratory pathogen, composed of g2na, the central domain of rsv g glycoprotein, and bb, an albumin binding domain of streptococcal protein g. bbg2na has a basic isoelectric point (pi 9.3) a ...200111457539
lipophilic quaternary ammonium salt acts as a mucosal adjuvant when co-administered by the nasal route with vaccine antigens.nasal administration of vaccines is an attractive approach which offers several significant advantages over traditional intramuscular vaccine delivery. these advantages include easier administration and induction of immune responses in the mucosal secretions of the body. in this study we describe a new potent nasal adjuvant, dimethyldioctadecylammonium bromide (dda), that induces both mucosal and systemic immune responses when co-administered with diphtheria toxoid (dt), tetanus toxoid (tt) and ...200111457550
r-mix cells are faster, at least as sensitive and marginally more costly than conventional cell lines for the detection of respiratory viruses.to evaluate shell vials of r-mix, a combination of mink lung cells and human adenocarcinoma cells (strains mv1lu and a549, respectively, diagnostic hybrids, athens, oh) to detect respiratory viruses from prospective clinical respiratory specimens and frozen stocks.200111418357
respiratory syncytial virus predisposes mice to augmented allergic airway responses via il-13-mediated mechanisms.the development of severe childhood asthma may be influenced by several factors including environmental and infectious stimuli. the causal relationship between infectious viral responses, such as respiratory syncytial virus (rsv), and severe asthma during early childhood is unclear. in these studies, the ability for an initial rsv infection to exacerbate and promote a more severe asthmatic-type response was investigated by combining established murine models of disease. we examined the ability o ...200111441116
functional analysis of recombinant respiratory syncytial virus deletion mutants lacking the small hydrophobic and/or attachment glycoprotein gene.respiratory syncytial virus (rsv) produces three envelope glycoproteins, the attachment glycoprotein (g), the fusion (f) protein, and the small hydrophobic (sh) protein. it had been assumed, by analogy with other paramyxoviruses, that the g and f proteins would be required for the first two steps of viral entry, attachment and fusion. however, following repeated passage in cell culture, a viable mutant rsv that lacked both the g and sh genes was isolated (r. a. karron, d. a. buonagurio, a. f. ge ...200111435561
benign outcome of rsv infection in children with cancer.high case-fatality rates have been reported among adults who develop respiratory syncytial virus (rsv) infection while being treated for oncologic diseases, particularly after bone marrow transplantation. previous reports of rsv infection among children with primary and acquired immunodeficiencies describe increased morbidity compared with that seen in immunocompetent children, but there have been few reports describing the outcome of rsv infection specifically among pediatric oncology patients.200111466719
[sequence analysis of phosphoprotein genes of respiratory syncytial virus field strains isolated in china].to get information about phosphoprotein (p) genes of rsv field strains isolated in china.200011471029
palivizumab in prevention of bronchiolitis: new preparation. moderate efficacy in some infants.(1) rsv infection, the main cause of bronchiolitis, can necessitate hospitalisation, especially of infants at risk, i.e. those with a history of prematurity or bronchodysplasia. no drug prevention has been available. (2) palivizumab, a monoclonal antibody directed against respiratory syncytial virus (rsv), is now marketed for preventing respiratory tract infection by rsv in certain infants. (3) the evaluation dossier barely answers the questions raised by the use of this drug. (4) the results o ...200011475494
rsv infection and bronchiolitis: who qualifies for prevention?(1) approximately 80% of cases of bronchiolitis appear to be due to respiratory syncytial virus (rsv). (2) overall, about 1% of cases of bronchiolitis lead to hospitalisation. this rises to about 25% in children with a history of severe prematurity, bronchopulmonary dysplasia or congenital heart disease.200011475495
cx3c chemokine mimicry by respiratory syncytial virus g glycoprotein.chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed c, cc, cxc and cx3c. chemokines have roles in immunity and inflammation that affect cell trafficking and activation of t cells as well as cells of the innate immune system. we report here cx3c chemokine mimicry for the g glycoprotein of respiratory syncytial virus (rsv) and show binding to cx3cr1--the specific receptor for the cx3c chemokine fractalkine--and induction of leukocyt ...200111477410
macrophage inflammatory protein-1alpha (not t helper type 2 cytokines) is associated with severe forms of respiratory syncytial virus bronchiolitis.it has been suggested that the pathogenesis of respiratory syncytial virus (rsv) infection is related to the development of t helper (th) type 2 cytokine responses. the presence of th1 and th2 cytokines and the chemokines macrophage inflammatory protein (mip)-1alpha and monocyte chemotactic protein (mcp)-1 were assessed by elisa in nasopharyngeal secretions of infants with rsv infection. infants with mild bronchiolitis had increased th1 cytokines and reduced th2 cytokines, compared with infants ...200111471095
the influence of prematurity and low birthweight on transplacental antibody transfer in a rural west african population.to determine the influence of prematurity and low birthweight (lbw) on transplacental antibody transfer.200111469946
[viral infection of the lower respiratory tract in hospitalized infants: etiology, clinical features and risk factors].the aim of this study was to assess the clinical and virological characteristics of lower respiratory tract (lrt) infection in hospitalized infants in spain and to identify clinical, radiological or laboratory parameters that could, on admission, be associated with a more severe clinical course.200111472660
k252a, an indrocarbazole derivative, causes the membrane of myoblasts to enter a fusion-capable state.k252a, an indrocarbazole derivative and protein kinase inhibitor, is reported to promote myogenic differentiation in c2 mouse myoblasts. we examined the effects of k252a on qm-rsv cells, quail myoblasts transformed with a temperature-sensitive mutant of rous sarcoma virus. k252a promoted myotube formation of qm-rsv cells. presumptive qm-rsv cells also formed multinucleated cells when exposed to k252a. however, the expression of myogenin, a muscle regulatory factor, was not stimulated in the pres ...200111478789
evaluation of the prodesse hexaplex multiplex pcr assay for direct detection of seven respiratory viruses in clinical specimens.we evaluated the hexaplex assay (prodesse, waukesha, wi) for the detection of 7 respiratory viruses (influenza a and b, parainfluenza 1-3, and respiratory syncytial virus [rsv] a and b). the hexaplex assay was performed on 300 respiratory samples during the 1999-2000 respiratory virus season. results of this assay were compared with shell vial cell culture and/or direct fluorescent antibody stain. the overall sensitivity and specificity of the assay were 96.6% and 94.1%, respectively. the respec ...200111488068
mammalian cell production of a respiratory syncytial virus (rsv) candidate vaccine recovered using a product-specific affinity column.the recombinant production of a respiratory syncytial virus (rsv) candidate vaccine bbg2na in baby hamster kidney cells (bhk-21 cells) was investigated. bbg2na consists of a serum-albumin-binding region (bb) fused to a 101-amino-acid fragment of the rsv g-protein. semliki forest virus-based expression vectors encoding both intracellular and secreted forms of bbg2na were constructed and found to be functional. affinity recovery of bbg2na employing human serum albumin columns was found to be ineff ...200111483151
antiviral activity and structural characteristics of the nonglycosylated central subdomain of human respiratory syncytial virus attachment (g) glycoprotein.segments of the cystine noose-containing nonglycosylated central subdomain, residues 149-197, of the attachment (g) glycoprotein of human respiratory syncytial virus (hrsv) have been assessed for impact on the cytopathic effect (cpe) of respiratory syncytial virus (rsv). nalpha-acetyl residues 149-197-amide (g149-197), g149-189, and g149-177 of the a2 strain of hrsv protected 50% of human epithelial hep-2 cells from the cpe of the a2 strain at concentrations (ic(50)) between 5 and 80 microm. cys ...200111487583
role of interleukin-12 and stat-4 in the regulation of airway inflammation and hyperreactivity in respiratory syncytial virus infection.respiratory syncytial virus (rsv) is a respiratory pathogen that can cause significant morbidity in infants and young children. interestingly, the majority of children who acquire a rsv infection do not exhibit severe symptoms. development of a th1 response has been associated with resolution of symptoms in viral infections and may explain mild rsv illness. the current study investigated the cytokine response observed in mild disease in c57bl/6 mice that had low airway resistance and mucus produ ...200111485921
community respiratory virus infections following lung transplantation.respiratory infections remain a significant cause of morbidity and mortality after lung transplantation. in addition to cytomegalovirus, the community respiratory viruses such as respiratory syncytial virus (rsv), parainfluenza virus (piv), influenza virus, and adenovirus, are important causes of infection in transplant recipients, often involve the lower respiratory tract, and may be associated with significant morbidity and mortality. in this review, we summarize the current state of knowledge ...200111493396
respiratory syncytial virus infections in previously healthy working adults.during 1975-1995, a total of 2960 healthy adults, 18-60 years of age, were prospectively evaluated for respiratory virus infections. of these subjects, 211 (7%) acquired respiratory syncytial virus (rsv) infection. the infections were symptomatic in 84% of subjects, involved only the upper respiratory tract in 74%, and included lower respiratory tract symptoms in 26%. overall, 40% of the subjects were febrile. lower respiratory tract signs developed in 26%. rsv illnesses were more prolonged than ...200111512084
(-)-terpestacin and l-tenuazonic acid, inducers of pigment and aerial mycelium formation by fusarium culmorum jp 15.surface cultures of fusarium culmorum jp15 were found to respond to extracts of other fungi by enhanced production of orange-red fusarubin pigments and formation of aerial mycelium. two inducers from strain ulocladium sp. hki 0226, the new (-)-terpestacin (1) and l-tenuazonic acid (2), were isolated. 1 inhibited syncytium formation by cells infected with respiratory syncytial virus (rsv).200111512450
etiology of childhood community acquired pneumonia and its implications for vaccination.pneumonia is an important cause of morbidity and mortality among children throughout the world. vaccines are available for some organisms, but they are underutilized and/or still in development. to evaluate the potential impact of vaccines, we review studies in which the etiology of childhood community-acquired pneumonia was recorded. in north america and europe (9 studies), the etiology of pneumonia was established in 62% of studied children (range 43%-88%) by use of noninvasive specific method ...200111493414
the influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental transfer of antibodies and igg subclasses in a rural west african population.two hundred thirteen mother-baby pairs in the gambia were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinemia on transplacental antibody transfer. antibody transfer for herpes simplex virus 1 (hsv-1), respiratory syncytial virus (rsv), and varicella-zoster virus (vzv) was significantly reduced by placental malaria infection by 69%, 58%, and 55%, respectively. maternal hypergammaglobulinemia was associated with a significant reduction in antibody ...200111494168
immunostimulating complexes (iscoms) for nasal vaccination.the immunostimulating complex (iscom) is documented as a strong adjuvant and delivery system for parenteral immunization. its effectiveness for mucosal immunization has also been proven with various incorporated antigens. lövgren et al. were the first to demonstrate the capacity of influenza virus iscoms to induce mucosal immune response and protection after one comparatively low nasal dose. further studies show that similar to cholera toxin (ct) and escherichia coli heat-labile toxin (lt), isco ...200111516786
production of transgenic quails with high frequency of germ-line transmission using vsv-g pseudotyped retroviral vector.we report here the production of transgenic quails using a replication-defective pantropic retroviral vector based on moloney murine leukemia virus (momlv) pseudotyped with vesicular stomatitis virus g protein (vsv-g). the retroviral vector was injected into laid quail embryos at the blastodermal stage, and the embryos were incubated to hatch to produce g(0) transgenic quails. among 134 embryos subjected to viral injection, 37 hatched. the viral vector sequence was detected in the tissues of all ...200111511080
activated, cytotoxic cd8(+) t lymphocytes contribute to the pathology of asthma death.this study investigates the presence of cd8(+) t lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (ad), seven asthmatic patients who died of unrelated causes (auc), and seven postmortem cases with no history of lung disease (control subjects). using immunohistochemical techniques, the cd8(+) cytotoxic t-cell population in pe ...200111520715
reliable detection of respiratory syncytial virus infection in children for adequate hospital infection control management.by using a rapid test for respiratory syncytial virus (rsv) detection (abbott testpack rsv), a number of patients were observed, showing repeatedly positive results over a period of up to 10 weeks. a prospective study was initiated to compare the rapid test with an antigen capture enzyme immunoassay (eia) and a nested reverse transcriptase pcr (rt-pcr) protocol for detection of rsv serotypes a and b. only respiratory samples from children exhibiting the prolonged presence of rsv (> or =5 days) a ...200111526141
construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine.recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. while vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. co-expression of il-4 increased vaccinia virus vector titres, while ifn-gamma co-expression reduced vaccinia virus replication in balb/c mice ...200111514719
modeling epidemics caused by respiratory syncytial virus (rsv).respiratory syncytial virus (rsv) is the most common cause of acute lower respiratory tract infection in children. in this paper we use models of rsv transmission to interpret the pattern of seasonal epidemics of rsv disease observed in different countries, and to estimate epidemic and eradication thresholds for rsv infection. we compare the standard sirs model with a more realistic model of rsv transmission in which individuals acquire immunity gradually after repeated exposure to infection. th ...200111520501
genetic diversity and molecular epidemiology of respiratory syncytial virus over four consecutive seasons in south africa: identification of new subgroup a and b genotypes.the molecular epidemiology of respiratory syncytial virus (rsv) was studied over four consecutive seasons (1997-2000) in a single tertiary hospital in south africa: 225 isolates were subgrouped by rt-pcr and the resulting products sequenced. subgroup a predominated in two seasons, while a and b co-circulated approximately equally in the other seasons. the nucleotide sequences of the c-terminal of the g-protein were compared to sequences representative of previously defined rsv genotypes. south a ...200111514720
cpg containing oligodeoxynucleotides are potent adjuvants for parenteral vaccination with the fusion (f) protein of respiratory syncytial virus (rsv).the feasibility of using oligodeoxynucleotides (odn) containing unmethylated cpg motifs as parenteral adjuvants for subunit vaccines against rsv was tested in balb/c mice. compared with immunization with natural f protein adsorbed to aluminum hydroxide (f/aloh) adjuvant alone, coadministration of f/aloh with cpg odn resulted in statistically significant increases in serum neutralization titers, an enhanced generation of splenic antigen-dependent killer cell precursors, and accelerated clearance ...200111535341
respiratory syncytial virus infections in autologous blood and marrow transplant recipients with breast cancer: combination therapy with aerosolized ribavirin and parenteral immunoglobulins.scant data are available concerning the impact and response to therapy of respiratory syncytial virus (rsv) infections in patients undergoing autologous blood and marrow transplantation (bmt) for breast cancer. during eight winter seasons from 1992-1993 to 1999-2000, nine (4%) of 249 such patients were hospitalized with rsv infections. six patients, including all five patients who were early post transplant in the pre-engraftment period, developed pneumonia and were treated with a combination of ...200111535995
long-term persistence and reactivation of t cell memory in the lung of mice infected with respiratory syncytial virus.in mice acutely infected with respiratory syncytial virus (rsv), more than 20% of pulmonary cd8(+) t cells, but only 2-3% of cd8(+) t cells in the draining lymph node secreted interferon-gamma in response to a single peptide. surprisingly, the percentage of virus-specific t cells in the lung remained at these high levels long after the acute infection. pulmonary memory t cells were further studied in a sensitive adoptive transfer system, which allows visualizing polyclonal cd4(+) and cd8(+) viru ...200111536155
occurrence and severity of infections caused by subgroup a and b respiratory syncytial virus in children in southeast brazil.the frequency and severity of infections caused by respiratory syncytial virus (rsv) were assessed in children <2 years of age seen at the emergency department. the frequency of rsv detection in the clinical virology laboratory during the past 3 years was also analyzed retrospectively. rsv was found in 21.6% (188/869) of the samples collected from children seen at the emergency department and was found to be more frequent during the autumn, being less frequent or negligible by midwinter. rsv sub ...200111536252
mechanism of selective inhibition of respiratory syncytial virus by a benzodithiin compound (rd3-0028).rd3-0028, a compound with a benzodithiin structure, was found to be a potent inhibitor of respiratory syncytial virus (rsv) replication. its action is specific; no activity is seen against influenza a virus, measles virus, herpes simplex virus type 1 or 2, or human cytomegalovirus. a time-dependent drug addition experiment indicated that the antiviral activity occurs in the late stage of the rsv replication cycle, since this compound completely inhibited syncytium formation even when added up to ...200111529559
different respiratory syncytial virus and quillaja saponin formulations induce murine peritoneal cells to express different proinflammatory cytokine profiles.the recognition of a pathogen or a vaccine antigen formulation by cells in the innate immune system leads to production of proinflammatory cytokines, which will determine the ensuing acquired immune response quantitatively and qualitatively. tumour necrosis factor (tnf)-alpha, interleukin (il)-1 and il-6 are the first set of cytokines produced upon such an encounter, which have roles both in protective immunity and immunopathogenesis evident with respiratory syncytial virus (rsv). rsv antigens i ...200111549417
expression of respiratory syncytial virus-induced chemokine gene networks in lower airway epithelial cells revealed by cdna microarrays.the paramyxovirus respiratory syncytial virus (rsv) is the primary etiologic agent of serious epidemic lower respiratory tract disease in infants, immunosuppressed patients, and the elderly. lower tract infection with rsv is characterized by a pronounced peribronchial mononuclear infiltrate, with eosinophilic and basophilic degranulation. because rsv replication is restricted to airway epithelial cells, where rsv replication induces potent expression of chemokines, the epithelium is postulated t ...200111533168
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