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the rice stripe virus pc4 functions in movement and foliar necrosis expression in nicotiana benthamiana.the rice stripe virus (rsv) pc4 has been determined as the viral movement protein (mp). in this study, the pc4 gene was cloned into a movement-deficient tobacco mosaic virus (tmv). the resulting hybrid tmv-pc4, in addition to spreading cell to cell in nicotiana tabacum, moved systemically and induced foliar necrosis in nicotiana benthamiana, indicating novel functions of the rsv mp. a systematic alanine-scanning mutagenesis study established the region k(122)-d(258) of the pc4 substantially asso ...201222305130
is chronic rhinosinusitis caused by persistent respiratory virus infection?many chronic rhinosinusitis (crs) patients recall an upper respiratory tract infection as the inciting event of their chronic illness. viral infections have been shown to cause obstruction of the osteomeatal complex, which is likely to be a critical step in the development of crs. there is clear overlap between the pathogenesis of crs and asthma. infections with respiratory viruses in childhood increase the risk of subsequently developing asthma. viral infections in established asthmatics are as ...201122287325
viral etiology in hospitalized children with acute lower respiratory tract infection.this study was performed to investigate the viral etiological agents, age distribution and clinical manifestations of lower respiratory tract infection (lrti) in hospitalized children. the viral etiology and clinical findings in 147 children (1 month to 5 years of age) hospitalized with acute lrti were evaluated. cell culture was used for isolation of influenza viruses and direct fluorescent antibody assay for parainfluenza viruses (pivs), respiratory syncytial virus (rsv) and adenoviruses (advs ...201122272450
microrna-221 modulates rsv replication in human bronchial epithelium by targeting ngf expression.early-life infection by respiratory syncytial virus (rsv) is associated with aberrant expression of the prototypical neurotrophin nerve growth factor (ngf) and its cognate receptors in human bronchial epithelium. however, the chain of events leading to this outcome, and its functional implications for the progression of the viral infection, has not been elucidated. this study sought to test the hypothesis that rsv infection modulates neurotrophic pathways in human airways by silencing the expres ...201222272270
proteins involved in extracellular matrix dynamics are associated with rsv disease severity.severity of respiratory syncytial virus (rsv) infection ranges widely. to what extent the local immune response is involved in rsv disease pathogenesis and which markers of this response are critical in determining disease severity is still matter of debate.the local immune response was studied in nasopharyngeal aspirates (npas) during rsv infection. forty-seven potential markers of disease severity were analysed in a screening cohort of rsv-infected infants with mild disease at home (n=8), hosp ...201222267765
molecular evolution of respiratory syncytial virus fusion gene, canada, 2006-2010.to assess molecular evolution of the respiratory syncytial virus (rsv) fusion gene, we analyzed rsv-positive specimens from 123 children in canada who did or did not receive rsv immunoprophylaxis (palivizumab) during 2006-2010. resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.201222264682
[development and characterization of a stable cell line expressing respiratory syncytial virus non-structural protein ns1].to develop a stable cell line that could express the rsv ns1, the full-length rsv ns1 gene was generated by rt-pcr amplification from respiratory syncytial virus. ns1 gene was ligated with pbabe-puro to construct the recombinant retroviral expression plasmid pbabe-ns1, which was cotransfected into 293ft packaging cells with pik packaging plasmid by calcium phosphate co-precipitation. the supernatant of 293ft was collected to infect hep-2 cells, the resulting cell clones stably expressing ns1 wer ...201122263272
respiratory syncytial virus infection in children with neuromuscular impairment.clinically obvious reasons why children with neurological impairment (nmi) may be more severely affected in case of a viral respiratory tract infection include reduced vital capacity due to muscular weakness or spastic scoliosis, disturbed clearance of respiratory excretions (weak coughing and dysphagia), inability to comply actively with physiotherapeutic interventions, recurrent micro-aspirations (gastroesophageal reflux disease, vomiting related to coughing), a history of frequent exposure to ...201122262988
risk factors for severe respiratory syncytial virus lower respiratory tract infection.rsv infection is a leading cause of lower respiratory tract infection, especially in high-risk infants with a history of prematurity, bronchopulmonary dysplasia (bpd), congenital heart disease (chd), neuromusculair impairment, immunodeficiency, and down syndrome. host related risk factors that have been identified to be associated with severe rsv related lower respiratory tract infection include young age below 6 months at the beginning of rsv season, multiple birth, male sex, low socioeconomic ...201122262987
epidemiology of respiratory syncytial virus infection in preterm infants.this review focuses on the burden of respiratory syncytial virus (rsv) infection in preterm infants with and without chronic lung disease (bronchopulmonary dysplasia, bpd). the year-to-year and seasonal variations in rsv activity are key aspects of rsv epidemiology, and knowledge/monitoring of local rsv activity is mandatory for guidance of prophylaxis with the monoclonal antibodies palivizumab and in the near future motavizumab. morbidity expressed in rates of hospitalizations attributable to r ...201122262986
diagnosis of respiratory syncytial virus infection.respiratory syncytial virus (rsv) is one of the most important pathogen causing severe lower respiratory tract infections in all age groups often requiring hospitalization. rapid laboratory diagnosis of rsv infection significantly decreases the use of antibiotics, additional laboratory testing and is associated with shorter hospitalization periods. the specific diagnosis of rsv infection is based on the detection of virus or viral antigens or virus specific nucleic acid sequences in respiratory ...201122262985
rnai-directed down-regulation of rsv results in increased resistance in rice (oryza sativa l.).rice stripe disease (rsd), caused by rice stripe virus (rsv), is a serious disease in temperate rice-growing areas. we have created an rnai construct containing coat protein gene (cp) and disease specific protein gene (sp) sequences from rsv. the rnai construct was transformed into two susceptible japonica varieties, suyunuo and guanglingxiangjing, to develop resistance against rsd. the homozygous progeny of rice plants in the t(5) and t(7) generations containing rnai constructs, after self-fert ...201222261864
[rhinoviruses. frequency in nonhospitalized children with acute respiratory infection].molecular methods for human rhinoviruses (hrv) have increased the sensitivity in their diagnosis. hrv may cause acute respiratory infections (ari) of the upper and lower respiratory tract. hrv infection during childhood is a predictor of asthma development. in this study, the hrv frequency in outpatient children with ari was determined, and their clinical features and previous conditions were evaluated. a total of 186 respiratory samples of children under 6 year old attending the cemic pediatric ...201222257453
effect of respiratory syncytial virus infection on regulated on activation, normal t-cells expressed and secreted production in a murine model of asthma.synthesis of regulated on activation, normal t-cells expressed and secreted (rantes) in the airway has previously been shown to be elevated after respiratory syncytial virus (rsv) infection. however, since few studies have examined whether rsv-infected asthma patients express a higher level of rantes than do normal individuals, we used a murine model of asthma to address this question.201122253642
epidemiology of respiratory viral infections in two long-term refugee camps in kenya, 2007-2010.abstract: background: refugees are at risk for poor outcomes from acute respiratory infections (ari) because of overcrowding, suboptimal living conditions, and malnutrition. we implemented surveillance for respiratory viruses in dadaab and kakuma refugee camps in kenya to characterize their role in the epidemiology of ari among refugees. methods: from 1 september 2007 through 31 august 2010, we obtained nasopharyngeal (np) and oropharyngeal (op) specimens from patients with influenza-like illne ...201222251705
role of neutralizing antibodies in adults with community-acquired pneumonia by respiratory syncytial virus.background. respiratory syncytial virus (rsv) has been implicated in the etiology of adult community-acquired pneumonia (cap). we investigated rsv infection in chilean adults with cap using direct viral detection, real-time reverse-transcription polymerase chain reaction (rtrt-pcr), and serology (microneutralization assay).methods. rsv, other respiratory viruses, and bacteria were studied by conventional and molecular techniques in adults aged ≥18 years presenting with cap to the healthcare faci ...201222238168
regulatory t cells expressing granzyme b play a critical role in controlling lung inflammation during acute viral infection.the inflammatory response to lung infections must be tightly regulated, enabling pathogen elimination while maintaining crucial gas exchange. using recently described "depletion of regulatory t cell" (dereg) mice, we found that selective depletion of regulatory t cells (tregs) during acute respiratory syncytial virus (rsv) infection enhanced viral clearance but increased weight loss, local cytokine and chemokine release, and t-cell activation and cellular influx into the lungs. conversely, infla ...201222236998
respiratory syncytial virus morbidity, premorbid factors, seasonality, and implications for prophylaxis.objectives: we investigated factors associated with morbidity and pediatric intensive care unit (picu) admission in children with respiratory syncytial virus (rsv) infection and explored seasonality and implication of prophylaxis. methods: a retrospective study between 2006 and 2008 of every child with a laboratory-confirmed rsv infection was included. results: six hundred seventy rsv admissions were identified. ten (1.5%) required picu admissions. children admitted to picu were younger than non ...201222227087
comparison of direct fluorescence assay and real-time rt-pcr as diagnostics for respiratory syncytial virus in young children.respiratory syncytial virus (rsv) is the major cause of lower respiratory tract infections in children worldwide. early detection of rsv is critical to initiate proper care. two methods, the direct fluorescence assay (dfa) and the real-time reverse-transcription polymerase chain reaction (rt-rt-pcr), that are used for rsv detection were compared. a total of 451 nasopharyngeal aspirates from children 5 years of age or less were tested for rsv using both methods. the overall prevalence rate of the ...201122220181
a systems approach for identifying resistance factors to rice stripe virus.rice stripe virus (rsv) causes disease that can severely affect the productivity of rice (oryza sativa). several rsv resistant cultivars have been developed. however, host factors conferring rsv resistance in these cultivars are still elusive. here, we present a systems approach for identifying potential rice resistance factors. we developed two near isogenic rsv resistant (nil22) and susceptible (nil37) lines and performed gene expression profiling of the two lines in rsv infected and uninfecte ...201222217248
activation of lymphocytes induced by bronchial epithelial cells with prolonged rsv infection.respiratory syncytial virus (rsv) preferentially infects airway epithelial cells,which might be responsible for susceptibility to asthma; however, the underlying mechanism is not clear. this study determined the activation of lymphocytes and drift of helper t (th) subsets induced by rsv-infected human bronchial epithelial cells (hbecs) in vitro. hbecs had prolonged infection with rsv, and lymphocytes isolated from human peripheral blood were co-cultured with rsv-infected hbecs. four groups were ...201122216085
independent structural domains in the paramyxovirus polymerase protein.all enzymatic activities required for genomic replication and transcription of nonsegmented negative strand rna viruses (nnsv or mononegavirales) are believed to be concentrated in the viral polymerase (l) protein. however, our insight into the organization of these different enzymatic activities into a bioactive tertiary structure remains rudimentary. fragments of mononegavirales polymerases analyzed to date cannot restore bioactivity through trans-complementation, unlike the related l proteins ...201222215662
il-13 regulates th17 secretion of il-17a in an il-10-dependent manner.il-13 is a central mediator of airway hyperresponsiveness and mucus expression, both hallmarks of asthma. il-13 is found in the sputum of patients with asthma; therefore, il-13 is an attractive drug target for treating asthma. we have shown previously that il-13 inhibits th17 cell production of il-17a and il-21 in vitro. th17 cells are associated with autoimmune diseases, host immune responses, and severe asthma. in this study, we extend our in vitro findings and determine that il-13 increases i ...201122210911
respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations.palivizumab utilization, compliance, and outcomes were examined in infants with preexisting medical diseases within the canadian registry database (caress) to aid in developing guidelines for potential "at-risk" infants in the future. infants who received ≥1 dose of palivizumab during the 2006-2010 respiratory syncytial virus (rsv) seasons at 29 sites were recruited and utilization, compliance, and outcomes related to respiratory infection/illness (ri) events were collected monthly. hazard ratio ...201122203430
Human rhinoviruses in severe respiratory disease in very low birth weight infants.Objectives: To assess incidence, burden of illness, and risk factors for human rhinoviruses (HRVs) in a cohort of very low birth weight (VLBW) infants. Methods: A 2-year prospective cohort study was conducted among VLBW premature infants in Buenos Aires, Argentina. Infants were enrolled in the NICU from June 1, 2003, to May 31, 2005, and managed monthly and with every acute respiratory illness (ARI) during the first year of life. Nasal wash samples were obtained during every respiratory episode ...201222201153
reduced inflammation and altered innate response in neonates during paramyxoviral infection.abstract: background: human infants are frequently hospitalized due to infection with the paramyxovirus respiratory syncytial virus (rsv). however, very little is known about the neonatal response to paramyxoviral infection. here, a neonatal model of paramyxoviral infection is developed using the mouse pathogen sendai virus (sev). results: adult mice infected with sev developed a predominantly neutrophilic inflammatory cell influx and a concomitant reduction in lung function, as determined by ...201122185352
infections caused by rsv among children and adults during two epidemic seasons.respiratory syncytial virus (rsv) is one of the most common causes of lower respiratory tract infections in young children, immunocompromised patients (children and adults), patients with chronic respiratory diseases and elderly people. reinfections occur throughout the life, but the severity of disease decreased with subsequent infection. the aim of this study was to analyze the frequency of rsv infections in two selected subpopulations: young children (below 5 y.) and adults with chronic respi ...201122184933
natural polymorphisms and resistance-associated mutations in the fusion protein of respiratory syncytial virus (rsv): effects on rsv susceptibility to palivizumab.specific mutations in respiratory syncytial virus (rsv) fusion protein can cause palivizumab resistance. we assessed the incidence of sequence polymorphisms and palivizumab resistance in clinical rsv isolates collected from immunoprophylaxis-naive subjects. polymorphisms were identified at low frequency, and only polymorphic mutations in antigenic site a (<1% of all polymorphisms) conferred palivizumab resistance.201122184728
the prophylaxis and treatment with antiviral agents of respiratory syncytial virus infections.in this review, we consider recent advances in the discovery and development of antiviral agents for respiratory syncytial virus (rsv) infections. a background to the various manifestations of human rsv infection and current treatments is provided. the technical, clinical and commercial issues surrounding the development of such antiviral agents are discussed.201122182737
in vitro inhibition of influenza virus infection by a crude extract from isatis indigotica root resulting in the prevention of viral attachment.isatis indigotica root (iir) has been widely used as a chinese medicinal herb to treat regular seasonal influenza over the long history of traditional chinese medicinal practice. however, its inhibitory activities against influenza virus infections along with the associated mechanisms have not been investigated comprehensively. in this study, the chemical nature, mode of action and in vitro anti-influenza activities of a crude extract ( ...201122179315
down syndrome and hospitalizations due to respiratory syncytial virus: a population-based study.objective: to assess the risk estimates for respiratory syncytial virus (rsv) hospitalization in children with down syndrome (ds) and the clinical features and severity of rsv lower respiratory tract infection (lrti) in hospitalized children. study design: statewide hospitalization data for children with ds for 1995 through 2006 from the colorado health and hospital association database were combined with birth data from the colorado department of public health and environment to obtain populati ...201122177993
[Etiology survey on virus of acute respiratory infection in Guangzhou from 2006 to 2009].To investigate the pathogens of acute respiratory infection (ARI) in Guangzhou from 2006 to 2009.201122177307
natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection.it is known that respiratory syncytial virus (rsv) is the main cause of bronchiolitis and pneumonia in young children. rsv infection often leads to severe acute lung immunopathology, but the underlying immune mechanisms are less elucidated. here, we found that rsv infection induced severe acute lung immune injury and promoted the accumulation and activation of lung natural killer (nk) cells at the early stage of infection in balb/c mice. activated lung nk cells highly expressed activating recept ...201122171263
performance on a multipathogen external quality assessment (eqa) panel by different mono- and multiplex nucleic acid amplification tests.an external quality assessment (eqa) panel consisting of a total of 48 samples in broncho alveolar lavage (bal) or transport medium was prepared in collaboration with quality control for molecular diagnostics (qcmd) (www.qcmd.org). the panel was used to assess the proficiency of the 3 laboratories that would be responsible to examine the 6000 samples to be collected in the grace network of excellence (www.grace-lrti.org). the main objective was to decide on the best performing testing approach f ...201122170925
increased replication of respiratory syncytial virus in the presence of cytokeratin 8 and 18.previously, it was reported that productive viral infection, viral protein synthesis, and viral rna replication of respiratory syncytial virus (rsv) operated efficiently in two human epithelial cell lines (hep-2 and a549), but not in a human mast-cell line, hmc-1. based on these observations, it was hypothesized that hmc-1 cells lack the machinery required for rsv replication. to identify the host factors required for rsv replication, cdna subtraction using a549, hep-2, and hmc-1 cells was perfo ...201222170560
airway ifn-γ production during rsv bronchiolitis is associated with eosinophilic inflammation.study objective: this study was designed to investigate the possible role of ifn-γ in eosinophil degranulation that occurs during respiratory syncytial virus (rsv) bronchiolitis. methods: sixty-seven infants, 2-24 months old and hospitalized with their first episode of acute rsv bronchiolitis, were selected for this study. eosinophil-active cytokine and chemokine profiles in nasal lavage supernatants taken within ...201122160185
rna-dependent rna polymerase 6 of rice (oryza sativa) plays role in host defense against negative-strand rna virus, rice stripe virus.rna-dependent rna polymerases (rdrs) from fungi, plants and some invertebrate animals play fundamental roles in antiviral defense. here, we investigated the role of rdr6 in the defense of economically important rice plants against a negative-strand rna virus (rice stripe virus, rsv) that causes enormous crop damage. in three independent transgenic lines (osrdr6as line a, b and c) in which osrdr6 transcription levels were reduced by 70-80% through antisense silencing, the infection and disease sy ...201122142475
simultaneous mutations in multi-viral proteins are required for soybean mosaic virus to gain virulence on soybean genotypes carrying different r genes.genetic resistance is the most effective and sustainable approach to the control of plant pathogens that are a major constraint to agriculture worldwide. in soybean, three dominant r genes, i.e., rsv1, rsv3 and rsv4, have been identified and deployed against soybean mosaic virus (smv) with strain-specificities. molecular identification of virulent determinants of smv on these resistance genes will provide essential information for the proper utilization of these resistance genes to protect soybe ...201122140577
suppression of ns3 and mp is important for the stable inheritance of rnai-mediated rice stripe virus (rsv) resistance obtained by targeting the fully complementary rsv-cp gene.rice stripe virus (rsv) is a viral disease that seriously impacts rice production in east asia, most notably in korea, china, and japan. highly rsv-resistant transgenic japonica rice plants were generated using a dsrnai construct designed to silence the entire sequence region of the rsv-cp gene. transgenic rice plants were inoculated with a population of viruliferous insects, small brown planthoppers (sbph), and their resistance was evaluated using elisa and an infection rate assay. a correlatio ...201122134721
partial depletion of natural cd4⁺cd25⁺ regulatory t cells with anti-cd25 antibody does not alter the course of acute influenza a virus infection.foxp3⁺cd4⁺ regulatory t cells represent a t cell subset with well-characterized immunosuppressive effects during immune homeostasis and chronic infections, and there is emerging evidence to suggest these cells temper pulmonary inflammation in response to acute viral infection. recent studies have demonstrated treatment with pc61 cd25-depleting antibody potentiates inflammation in a murine model of rsv infection, while paradoxically delaying recruitment of cd8⁺ t cells to the site of inflammation ...201122125630
Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands.Respiratory syncytial virus (RSV) infection is the most important viral cause of severe respiratory disease in infants and children worldwide and also forms a serious threat in the elderly. The development of RSV vaccine, however, has been hampered by the disastrous outcome of an earlier trial using an inactivated and parenterally administered RSV vaccine which did not confer protection but rather primed for enhanced disease upon natural infection. Mucosal administration does not seem to prime f ...201222120195
isolation of influenza viruses in mdck 33016pf cells and clearance of contaminating respiratory viruses.this paper summarizes results obtained by multiplex pcr screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in mdck 33016pf cells. using the resplexii v2.0 (qiagen) multiplex pcr, 393 positive results were obtained in 468 clinical samples collected during an influenza season in germany. the overall distribution of positive results was influenza a 42.0%, influenza b 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronaviru ...201222119922
A sensitive real-time PCR for detection and subgrouping of human respiratory syncytial virus.Improved diagnostic tools for rapid detection, quantitation, and subgrouping of human respiratory syncytial virus (RSV) are needed to aid the development and evaluation of novel intervention strategies. A quantitative real-time RT-PCR using specific locked nucleic acid (LNA) probes was developed to identify RSV and to distinguish RSV subgroups A and B (RSV LNA assay). RSV subgroup diversity and the relationship between viral load and disease severity in confirmed RSV infections were also explore ...201222119628
sendai virus-based rsv vaccine protects african green monkeys from rsv infection.respiratory syncytial virus (rsv) is a serious disease of children, responsible for an estimated 160,000 deaths per year worldwide. despite the ongoing need for global prevention of rsv and decades of research, there remains no licensed vaccine. sendai virus (sev) is a mouse parainfluenza virus-type 1 which has been previously shown to confer protection against its human cousin, human parainfluenza virus-type 1 in african green monkeys (agm). here is described the study of a rsv vaccine (sevrsv) ...201122119594
the hiv-1 nucleocapsid protein does not function as a transcriptional activator on its own cognate promoter.the human immunodeficiency virus type 1 (hiv-1) nucleocapsid (nc) is a multifunctional, zinc finger-containing protein known to be involved in almost every step of the viral life cycle. we therefore examined the effects of nc in vivo as a transcription activator on the basal transcriptional activity of the hiv-1 u3 and rous sarcoma virus (rsv) promoters, as well as hiv-1 long terminal repeats (ltrs) such as the u3r and u3ru5 regions, using promoter-fused reporter gene assays, western blot analys ...201122119402
high frequency of human bocavirus 1 dna in infants and adults with lower acute respiratory infection.human bocavirus (hbov) is a parvovirus with a possible etiological role in respiratory disease currently under investigation. we detected hbov1 in children and adults hospitalized with acute disease of the lower respiratory tract. hbov genome was detected by pcr in nasopharyngeal swabs collected from 75 patients aged 0-89 years old during 2010. hbov was found in 17/75 (22.7%) patients, 64.7% of them infants younger than 1 year old and 29.4% adults older than 30 years (the bimodal age distribu ...201122116985
tumorigenesis related to retroviral infections.retroviral infections are considered important risk factors for cancer development in humans since approximately 15-20% of cancer worldwide is caused by an infectious agent. this report discusses the most established oncogenic retroviruses, including human immunodeficiency virus (hiv), human t-cell leukemia virus (htlv-1 and -2), rous sarcoma virus (rsv), abelson murine leukemia virus (a-mulv), moloney murine leukemia virus (m-mulv), murine mammary tumor virus (mmtv), bovine leukemia virus, (blv ...201122112727
antiviral activity in vitro of two preparations of the herbal medicinal product sinupret® against viruses causing respiratory infections.sinupret(®), a herbal medicinal product made from gentian root, primula flower, elder flower, sorrel herb, and verbena herb is frequently used in the treatment of acute and chronic rhinosinusitis and respiratory viral infections such as common cold. to date little is known about its potential antiviral activity. therefore experiments have been performed to measure the antiviral activity of sinupret(®) oral drops (hereinafter referred to as "oral drops") and sinupret(®) dry extract (hereinafter r ...201122112724
mycoplasma pneumoniae respiratory tract infections among greek children.background: m. pneumoniae is a common cause of respiratory tract infections (rtis) of variable severity especially in children. new diagnostic techniques offered more reliable information about the epidemiology of infection by this pathogen.aim: the aim of this study was to investigate the prevalence and epidemiology of acute m. pneumoniae infections among greek children hospitalized for rtis using more advanced techniques.material and methods: the study included 225 greek children hospitalized ...201122110297
seasonal variations in clostridium difficile infections are associated with influenza and respiratory syncytial virus activity independently of antibiotic prescriptions: a time series analysis in quebec, canada.seasonal variations in clostridium difficile-associated diarrhea (cdad), with a higher incidence occurring during winter months, have been reported. although winter epidemics of respiratory viruses may be temporally associated with an increase in cdad morbidity, we hypothesized that this association is mainly due to increased antibiotic use for respiratory infections. the objective of this study was to evaluate the effect of the two most frequent respiratory viruses (influenza virus and respirat ...201122106208
Structures of respiratory syncytial virus nucleocapsid protein from two crystal forms: details of potential packing interactions in the native helical form.Respiratory syncytial virus (RSV) is a frequent cause of respiratory illness in infants, but there is currently no vaccine nor effective drug treatment against this virus. The RSV RNA genome is encapsidated and protected by a nucleocapsid protein; this RNA-nucleocapsid complex serves as a template for viral replication. Interest in the nucleocapsid protein has increased owing to its recent identification as the target site for novel anti-RSV compounds. The crystal structure of human respiratory ...201122102022
potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate.a number of different viruses including respiratory syncytial virus (rsv) initiate infection of cells by binding to cell surface glycosaminoglycans and sulfated oligo- and polysaccharide mimetics of these receptors exhibit potent antiviral activity in cultured cells. we investigated whether the introduction of different lipophilic groups to the reducing end of sulfated oligosaccharides would modulate their anti-rsv activity. our results demonstrate that the cholestanol-conjugated tetrasaccharide ...201222101246
serosurvey of bacterial and viral respiratory pathogens among deployed u.s. service members.respiratory illnesses can cause substantial morbidity during military deployments. bordetella pertussis, chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, parainfluenza, and respiratory syncytial virus (rsv) are hypothesized causes.201122099233
clinical and radiological features of respiratory syncytial virus in solid organ transplant recipients: a single-center experience.background: respiratory syncytial virus (rsv) infections range from upper respiratory illness to severe lower respiratory disease. there is no universally accepted treatment for rsv in solid organ transplant (sot) recipients. methods: retrospective review of adult sot patients with rsv infections, between january 2007 and december 2009, in a single transplant center was performed. results: during the 3-year period, a total of 24 adults developed rsv infection, including 12 (50%) sot recipients ( ...201122093238
low neonatal toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis.atopic dermatitis (ad) and respiratory syncytial virus lower respiratory tract infection (rsv lrti) are common diseases during early life. impaired th1-cell polarizing toll-like receptor (tlr) responses play an important role in the pathogenesis of both diseases. neonatal tlr-mediated production of th1-type cytokines is decreased at birth, but rapidly increases during the first month of life.201122092594
Cholesterol-rich Microdomains as Docking Platforms for Respiratory Syncytial Virus in Normal Human Bronchial Epithelial Cells.Respiratory syncytial virus (RSV) is one of the major causes of respiratory infections in children and it is the main pathogen causing bronchiolitis in infants. The binding and entry mechanism by which RSV infects respiratory epithelial cells has not yet been determined. In this study, the earliest stages of RSV infection in normal human bronchial epithelial cells were probed by tracking virions with fluorescent lipophilic dyes in their membranes. Virions colocalized with cholesterol-containing ...201122090136
respiratory syncytial virus glycoprotein g interacts with dc-sign and l-sign to activate erk1 and erk2.respiratory syncytial virus (rsv) interaction with epithelial and dendritic cells (dcs) is known to require divalent cations, suggesting involvement of c-type lectins. rsv infection and maturation of primary human dcs are reduced in a dose-dependent manner by edta. therefore, we asked whether rsv infection involves dc-sign (cd209) or its isoform l-sign (cd299) (dc-sign/r). using surface plasmon resonance analysis, we demonstrated that the attachment g glycoprotein of rsv binds both dc- and l-sig ...201122090124
Cholesterol-rich lipid rafts are required for release of infectious human respiratory syncytial virus particles.Cholesterol and sphingolipid enriched lipid raft micro-domains in the plasma membrane play an important role in the life-cycle of numerous enveloped viruses. Although human respiratory syncytial virus (RSV) proteins associate with the raft domains of infected cells and rafts are incorporated in RSV virion particles, the functional role of raft during RSV infection was unknown. In the current study we have identified rafts as an essential component of host cell that is required for RSV infection. ...201222088217
[respiratory syncytial virus infection in hematopoietic stem cell transplantation recipients with primary immunodeficiencies].to understand the clinical characteristics and outcome associated with respiratory syncytial virus (rsv) infection in hematopoietic stem cell transplantation (hsct) recipients with primary immunodeficiencies (pids).201122088176
a respiratory syncytial virus isolate enables the testing of virucidal products.the respiratory syncytial virus (rsv) is known as a major cause of respiratory infections and nosocomial diseases. testing this virus is rather difficult due to the problems encountered in producing it at a high titer without using any purification method. a rsv isolate which replicates to high level on a hep-2 cell line with an infectious titer of at least 10(7)tcid(50)ml(-1) in culture supernatant fluids has been identified. thanks to this isolate, the virucidal effects of two products, a hand ...201122079427
use of data linkage to investigate the aetiology of acute lower respiratory infection hospitalisations in children.aim:  to document the aetiology of acute lower respiratory infection (alri) hospitalisations in western australian children by linking population-based laboratory data with hospital morbidity data. methods:  data from all alri hospitalisations and laboratory records related to respiratory pathogens between 2000 and 2005 were extracted and linked through a population-based record linkage system. the proportion of specimens that were positive for each respiratory viral or bacterial pathogen was do ...201122077532
quinoline tricyclic derivatives. design, synthesis and evaluation of the antiviral activity of three new classes of rna-dependent rna polymerase inhibitors.in this study three new classes of linear n-tricyclic compounds, derived by condensation of the quinoline nucleus with 1,2,3-triazole, imidazole or pyrazine, were synthesized, obtaining triazolo[4,5-g]quinolines, imidazo[4,5-g]quinolines and pyrido[2,3-g]quinoxalines, respectively. title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against rna viruses representative of the three genera of the flaviviridae family, that is bvdv (pestivirus), yfv (flavivirus) a ...201122047799
the anti-apoptotic effect of respiratory syncytial virus on human peripheral blood neutrophils is mediated by a monocyte derived soluble factor.respiratory syncytial virus (rsv) causes annual epidemics of respiratory disease particularly affecting infants. the associated airway inflammation is characterized by an intense neutrophilia. this neutrophilic inflammation appears to be responsible for much of the pathology and symptoms. previous work from our group had shown that there are factors within the airways of infants with rsv bronchiolitis that inhibit neutrophil apoptosis. this study was undertaken to determine if rsv can directly a ...201122046209
[Antibody responses induced by mucosal DNA vaccine encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium].In order to investigate antibody responses by musosal DNA vaccines encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium aroA strain SL7207 (SL7207) via intranasal or intragastric routes.201122043798
clinical and epidemiological characteristics of respiratory syncytial virus and influenza virus associated hospitalization in urban thai infants.respiratory syncytial virus (rsv) and influenza infections are among the leading cause of hospitalized lower respiratory tract infections (lrti) in children especially among those younger than 1 year of age. few descriptions of these 2 important viruses in thai children less than 1 year of age have been published.201122043771
dp2 (crth2) antagonism reduces ocular inflammation induced by allergen challenge and respiratory syncytial virus.background: allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. the early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by th2 cells and eosinophils. prostaglandin d(2) (pgd(2)), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the ...201122042170
relationship between the population incidence of febrile convulsions in young children in sydney, australia and seasonal epidemics of influenza and respiratory syncytial virus, 2003-2010: a time series analysis.in 2010, intense focus was brought to bear on febrile convulsions in australian children particularly in relation to influenza vaccination. febrile convulsions are relatively common in infants and can lead to hospital admission and severe outcomes. we aimed to examine the relationships between the population incidence of febrile convulsions and influenza and respiratory syncytial virus (rsv) seasonal epidemics in children less than six years of age in sydney australia using routinely collected s ...201122029484
five proteins of laodelphax striatellus are potentially involved in the interactions between rice stripe virus and vector.rice stripe virus (rsv) is the type member of the genus tenuivirus, which relies on the small brown planthopper (laodelphax striatellus fallén) for its transmission in a persistent, circulative-propagative manner. to be transmitted, virus must cross the midgut and salivary glands epithelial barriers in a transcytosis mechanism where vector receptors interact with virions, and as propagative virus, rsv need utilize host components to complete viral propagation in vector cells. at present, these m ...201122028913
inosine-containing rna is a novel innate immune recognition element and reduces rsv infection.during viral infections, single- and double-stranded rna (ssrna and dsrna) are recognized by the host and induce innate immune responses. the cellular enzyme adar-1 (adenosine deaminase acting on rna-1) activation in virally infected cells leads to presence of inosine-containing rna (ino-rna). here we report that ss-ino-rna is a novel viral recognition element. we synthesized unmodified ssrna and ssrna that had 6% to16% inosine residues. the results showed that in primary human cells, or in mice ...201122028885
Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions.The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8?µg/ml (0.41-22?nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6?µg/ ...201222028179
Human bocavirus and other respiratory viral infections in a 2-year cohort of hospitalized children.Human bocavirus (HBoV) infection is reported worldwide and may cause severe respiratory tract infections. The aim of the present study was to assess the prevalence of HBoV, and other respiratory viral pathogens, in a 2-year retrospective study of children admitted to hospital, and to investigate whether viral loads of HBoV DNA were associated with severity of infection. Between April 2007 and March 2009, 891 respiratory samples from 760 children admitted to hospital with acute respiratory tract ...201222028039
CT of viral lower respiratory tract infections in adults: comparison among viral organisms and between viral and bacterial infections.We retrospectively compared the CT findings of consecutive viral and bacterial lower respiratory tract infections (LRTIs) to determine their imaging appearance and any definable differences among the causative viruses and between the viral and bacterial infections.201122021500
impact of influenza during the post-pandemic season: epidemiological picture from syndromic and virological surveillance.following the observation that 1 or 2 pandemic peak due to the circulation ofahinlv had occurred in most countries and in most world health organization (who) regions, who declared on august 10"h, 2010 that the world was moving into the post-pandemic period, whose surveillance presents considerable interest both from epidemiological and clinical point of view. we described the epidemiological picture emerged from syndromic and virological surveillance during the post-pandemic season in liguria, ...201122010543
Respiratory syncytial virus--the unrecognised cause of health and economic burden among young children in Australia.Respiratory syncytial virus (RSV) presents very similar to influenza and is the principle cause of bronchiolitis in infants and young children worldwide. Yet, there is no systematic monitoring of RSV activity in Australia. This study uses existing published data sources to estimate incidence, hospitalisation rates, and associated costs of RSV among young children in Australia. Published reports from the Laboratory Virology and Serology Reporting Scheme, a passive voluntary surveillance system, a ...201122010512
respiratory syncytial virus (rsv) community-acquired pneumonia (cap) in a hospitalized adult with human immunodeficiency virus (hiv) mimicking influenza a and pneumocystis (carinii) jiroveci pneumonia (pcp).respiratory syncytial virus (rsv) is an important cause of lower respiratory tract infections in young children, the elderly, and immunocompromised hosts, but rsv is a rare cause of community-acquired pneumonia (cap) in hospitalized adults with human immunodeficiency virus (hiv). in patients with hiv, cap is most frequently attributable to the usual bacterial respiratory pathogens that cause cap in immunocompetent hosts, eg, streptococcuspneumoniae or hemophilus influenzae. adults with hiv are a ...201222005289
respiratory syncytial virus hospitalization trends in infants with chronic lung disease of infancy, 1998-2008.infants with chronic lung disease of infancy (cldi) are at high risk for severe respiratory syncytial virus (rsv) illness requiring hospitalization. palivizumab was first licensed in 1998 for the prevention of rsv disease in high-risk infants, including those with cldi. we performed a retrospective cohort study of all hospitalized children with cldi aged <2 years between 1998 and 2008 in the usa to determine trends in rates of hospitalizations due to rsv (rsvh) since the launch of palivizumab.201122003308
comparative dynamics, morbidity and mortality burden of pediatric viral respiratory infections in an equatorial city.: although acute respiratory infections (aris) are the global leading cause of pediatric morbidity and mortality, the relative impact of viral pathogens on pediatric aris is still poorly understood, especially in equatorial settings. long-term studies of multiple viruses concurrently circulating in these regions are still lacking. here, we report the results of a systematic prospective surveillance of multiple respiratory viruses conducted every weekday for nearly a decade in an equatorial city ...201122001966
whole genome sequencing and evolutionary analysis of human respiratory syncytial virus a and b from milwaukee, wi 1998-2010.respiratory syncytial virus (rsv) is the leading cause of lower respiratory-tract infections in infants and young children worldwide. despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for rsv group a and group b respectively.201121998661
nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion.despite the medical importance of respiratory syncytial virus (rsv) infections, there is no vaccine or therapeutic agent available. prophylactic administration of palivizumab, a humanized monoclonal rsv fusion (f) protein-specific antibody, can protect high-risk children. previously, we have demonstrated that rsv can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the rsv protein f (f-vhhb nanobodies). here, we investigated the mechanism b ...201121998474
comparison of the filmarray respiratory panel and prodesse real-time pcr assays for detection of respiratory pathogens.we compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the filmarray respiratory panel (rp) multiplex pcr assay (idaho technology, inc., salt lake city, ut) with those of the food and drug administration (fda)-cleared prodesse proflu+, profast+, proparaflu+, pro hmpv+, and proadeno+ real-time pcr assays (gen-probe, san diego, ca). the assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children u ...201121998418
renal transplant with bronchiolitis obliterans organizing pneumonia (boop) attributable to tacrolimus and herpes simplex virus (hsv) pneumonia.background: solid organ transplants (sots) may be complicated by a wide variety of infectious and noninfectious pulmonary disorders. transplant patients receive immunosuppressive drugs to prevent rejection, but these drugs also predispose them to infection. because immunosuppressive therapy impairs t-lymphocyte function, ie, cell-mediated immunity, such therapy, not surprisingly, predisposes patients to intracellular pulmonary pathogens. community-acquired pneumonia (cap) in patients with sot us ...201121996615
exploratory spatial analysis of in vitro respiratory syncytial virus co-infections.the cell response to virus infection and virus perturbation of that response is dynamic and is reflected by changes in cell susceptibility to infection. in this study, we evaluated the response of human epithelial cells to sequential infections with human respiratory syncytial virus strains a2 and b to determine if a primary infection with one strain will impact the ability of cells to be infected with the second as a function of virus strain and time elapsed between the two exposures. infected ...201021994640
protein kinase r is a novel mediator of cd40 signaling and plays a critical role in modulating immunoglobulin expression during respiratory syncytial virus infection.effective immunoglobulin responses play a vital role in protection against most pathogens. however, the molecular mediators and mechanisms responsible for signaling and selective expression of immunoglobulin types remain to be elucidated. previous studies in our laboratory have demonstrated that protein kinase r (pkr) plays a crucial role in ige responses to double-stranded rna (dsrna) in vitro. in this study, we show that pkr plays a critical role in igg expression both in vivo and in vitro. pk ...201121994357
respiratory syncytial virus vaccine development.respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract viral disease in infants and young children. presently, there are no explicit recommendations for rsv treatment apart from supportive care. the virus is therefore responsible for an estimated 160,000 deaths per year worldwide. despite half a century of dedicated research, there remains no licensed vaccine product. herein are described past and current efforts to harness innate and adaptive immune potentials to comb ...201121988307
comparison of differing cytopathic effects in human airway epithelium of parainfluenza virus 5 (w3a), parainfluenza virus type 3, and respiratory syncytial virus.parainfluenza virus 5 (piv5) infects a wide range of animals including dogs, pigs, cats, and humans; however, its association with disease in humans remains controversial. in contrast to parainfluenza virus 3 (piv3) or respiratory syncytial virus (rsv), piv5 is remarkably non-cytopathic in monolayer cultures of immortalized epithelial cells. to compare the cytopathology produced by these viruses in a relevant human tissue, we infected an in vitro model of human ciliated airway epithelium and mea ...201121986028
The post-infection outcomes of influenza and acute respiratory infection in patients above 50 years of age in Japan: an observational study.Please cite this paper as: Ikematsu et al. (2011) The post-infection outcomes of influenza and acute respiratory infection in patients above 50 years of age in Japan: an observational study. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00296.x. Objectives Influenza can be a serious illness, especially for older people, and reducing the impact of influenza in elderly is important. The objective of this study was to estimate the prevalence and postinfection outcomes of in ...201121985038
effect of glucocorticoid in mice of asthma induced by ovalbumin sensitisation and rsv infection.to investigate the inflammatory changes and the airway hyper-responsiveness in the asthma mouse model infected by respiratory syncytial virus and elucidate the relationship between the infection and the effect of glucocorticoid.201121980833
immunoprotectivity of hla-a2 ctl peptides derived from respiratory syncytial virus fusion protein in hla-a2 transgenic mouse.identification of hla-restricted cd8+ t cell epitopes is important to study rsv-induced immunity and illness. we algorithmically analyzed the sequence of the fusion protein (f) of respiratory syncytial virus (rsv) and generated synthetic peptides that can potentially bind to hla-a*0201. four out of the twenty-five 9-mer peptides tested: peptides 3 (f33-41), 13 (f214-222), 14 (f273-281), and 23 (f559-567), were found to bind to hla-a*0201 with moderate to high affinity and were capable of inducin ...201121980478
Purification of human respiratory syncytial virus fusion glycoprotein.Human respiratory syncytial virus (RSV) fusion glycoprotein (F) elicits neutralizing antibodies to RSV and has therefore attracted much attention as a suitable candidate antigen in the development of gene-based vaccines against RSV infections. However, a major obstacle in vaccine development has been the problem of antigen purification. To address this problem, we have developed a new method that combines sucrose gradient ultracentrifugation and a two-step chromatographic process, to purify RSV ...201221979254
a simplified immune suppression scheme leads to persistent micro-dystrophin expression in duchenne muscular dystrophy dogs.abstract highly abbreviated micro-dystrophin genes have been intensively studied for duchenne muscular dystrophy (dmd) gene therapy. following adeno-associated virus (aav) gene transfer, robust microgene expression is achieved in murine dmd models in the absence of immune suppression. interestingly, a recent study suggests that aav gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycop ...201121967249
The insertion of fluorescent proteins in a variable region of respiratory syncytial virus L polymerase results in fluorescent and functional enzymes but with reduced activities.The respiratory syncytial virus (RSV) Large protein L is the catalytic subunit of the RNA-dependent RNA polymerase complex. Currently, no structural information is available for RSV L. Sequence alignments of L protein from human and bovine strains of RSV revealed the existence of two variable regions, VR1 and VR2. Following comparison with morbillivirus and rhabdovirus L genes, VR2, which is located between domains V and VI, was chosen as an insertion site for sequences encoding the epitope tag ...201121966341
progress in understanding and controlling respiratory syncytial virus: still crazy after all these years.human respiratory syncytial virus (rsv) is a ubiquitous pathogen that infects everyone worldwide early in life and is a leading cause of severe lower respiratory tract disease in the pediatric population as well as in the elderly and in profoundly immunosuppressed individuals. rsv is an enveloped, nonsegmented negative-sense rna virus that is classified in family paramyxoviridae and is one of its more complex members. although the replicative cycle of rsv follows the general pattern of the param ...201121963675
Cost-effectiveness of Palivizumab for Respiratory Syncytial Virus Infection in High-risk Children, Based on Long-term Epidemiologic Data From Austria.: To assess the cost-effectiveness of palivizumab, a monoclonal antibody against respiratory syncytial virus (RSV), in infants at high risk for severe RSV lower respiratory tract infection, such as premature infants, infants with bronchopulmonary dysplasia, and those with congenital heart disease, based on long-term epidemiologic data from Austria.201121960187
Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings.Please cite this paper as: Burns et al. (2011) Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00292.x. Background Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symp ...201121955319
distinguishing characteristics between pandemic 2009-2010 influenza a (h1n1) and other viruses in patients hospitalized with respiratory illness.differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza a h1n1 (ph1n1) compared to other respiratory viruses have not been fully elucidated.201121949746
human metapneumovirus inhibits ifn-β signaling by downregulating jak1 and tyk2 cellular levels.human metapneumovirus (hmpv), a leading cause of respiratory tract infections in infants, inhibits type i interferon (ifn) signaling by an unidentified mechanism. in this study, we showed that infection of airway epithelial cells with hmpv decreased cellular level of janus tyrosine kinase (jak1) and tyrosine kinase 2 (tyk2), due to enhanced proteosomal degradation and reduced gene transcription. in addition, hmpv infection also reduced the surface expression of type i ifn receptor (ifnar). these ...201121949722
relationship between lower respiratory tract infections caused by respiratory syncytial virus and subsequent development of asthma in japanese children.several studies in western countries have found that lower respiratory tract infections (lrtis) caused by the respiratory syncytial virus (rsv) in infancy may subsequently trigger the development of asthma. in this study, we enrolled 262 infants under the age of 3 who had been admitted to our hospital with lrti between september 2002 and august 2003. rsv infection was diagnosed in these patients using an rsv rapid diagnostic kit and by measuring antibody titers in paired serum samples. in march ...201121937828
resveratrol-mediated gamma interferon reduction prevents airway inflammation and airway hyperresponsiveness in respiratory syncytial virus-infected immunocompromised mice.respiratory syncytial virus (rsv) is the most important cause of severe, lower respiratory tract infections in infants, and rsv infections have been associated with chronic wheezing and asthma during childhood. however, the mechanism of rsv-induced airway inflammation and airway hyperresponsiveness (ahr) is poorly understood. furthermore, there are presently neither effective vaccines nor drugs available for the prevention or treatment of rsv infections. in this study, we investigated the effect ...201121937650
Label-free quantitative proteomics reveals regulation of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) and 5'-3'-exoribonuclease 2 (XRN2) during respiratory syncytial virus infection.ABSTRACT: A large quantitative study was carried out to compare the proteome of respiratory syncytial virus (RSV) infected versus uninfected cells in order to determine novel pathways regulated during viral infection. RSV infected and mock-infected HEp2 cells were lysed and proteins separated by preparative isoelectric focussing using offgel fractionation. Following tryptic digestion, purified peptides were characterized using label-free quantitative expression profiling by nano-ultra performanc ...201121933386
Phase 1 Study of the Safety and Immunogenicity of a Live, Attenuated Respiratory Syncytial Virus and Parainfluenza Virus Type 3 Vaccine in Seronegative Children.BACKGROUND:: Respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are important causes of lower respiratory tract illness and hospitalization in young children. Currently, there is no licensed vaccine against RSV or PIV3. METHODS:: In this randomized, phase 1, double-blind, placebo-controlled, dose-escalating study, 49 healthy RSV/PIV3-seronegative children 6 to <24 months of age were randomized 2:1 to receive 3 doses (at 104, 105, or 106 median tissue culture infective dose [ ...201121926667
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