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multiplex molecular detection of respiratory pathogens in children with asthma exacerbation.up to 80% of asthma exacerbations in white children are associated with viral upper respiratory infections. the relative importance of different respiratory pathogens and relevant microbiological data in asian children are unclear. this study elucidated the epidemiology of respiratory infections in hong kong children with asthma exacerbation.201019749009
the human rhinovirus: human-pathological impact, mechanisms of antirhinoviral agents, and strategies for their discovery.as the major etiological agent of the common cold, human rhinoviruses (hrv) cause millions of lost working and school days annually. moreover, clinical studies proved an association between harmless upper respiratory tract infections and more severe diseases e.g. sinusitis, asthma, and chronic obstructive pulmonary disease. both the medicinal and socio-economic impact of hrv infections and the lack of antiviral drugs substantiate the need for intensive antiviral research. a common structural fea ...201119714577
cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection.exposure to cigarette smoke is associated with a significant increase in the risk for respiratory viral infections. the airway epithelium is the primary target for both cigarette smoke and respiratory viral infection. we investigated the effects of cigarette smoke on the response of airway epithelial cells to rhinovirus infection. we found that pre-exposure of beas-2b cells or primary normal human bronchial epithelial cells (nhbes) to cigarette smoke extract (cse) reduced the induction of mrna o ...201120224072
complete coding sequence characterization and comparative analysis of the putative novel human rhinovirus (hrv) species c and b.human rhinoviruses (hrvs) are well recognized viral pathogens associated with acute respiratory tract illnesses (rtis) abundant worldwide. although recent studies have phylogenetically identified the new hrv species (hrv-c), data on molecular epidemiology, genetic diversity, and clinical manifestation have been limited.201121214911
the relationship between respiratory viral loads and diagnosis in children presenting to a pediatric hospital emergency department.respiratory viral infections account for a considerable proportion of pediatric emergency room visits. illnesses range in severity from mild upper respiratory tract infections to serious lower respiratory tract infections (lrti). the relationship between viral load and specific viruses to clinical diagnosis made by physicians in this setting is poorly understood.201120980931
antibodies induced with recombinant vp1 from human rhinovirus exhibit cross-neutralisation.human rhinoviruses (hrvs) are the major cause of the common cold and account for 30-50% of all acute respiratory illnesses. although hrv infections are usually harmless and invade only the upper respiratory tract, several studies demonstrate that hrv is involved in the exacerbation of asthma. vp1 is one of the surface-exposed proteins of the viral capsid that is important for the binding of rhinoviruses to the corresponding receptors on human cells. here we investigated its potential usefulness ...201120530036
usefulness of published pcr primers in detecting human rhinovirus infection.we conducted a preliminary comparison of the relative sensitivity of a cross-section of published human rhinovirus (hrv)-specific pcr primer pairs, varying the oligonucleotides and annealing temperature. none of the pairs could detect all hrvs in 2 panels of genotyped clinical specimens; >1 pcr is required for accurate description of hrv epidemiology.201121291610
association between human rhinovirus c and severity of acute asthma in children.a new and potentially more pathogenic group of human rhinovirus (hrv), group c (hrvc), has recently been discovered. we hypothesised that hrvc would be present in children with acute asthma and cause more severe attacks than other viruses or hrv groups. children with acute asthma (n = 128; age 2-16 yrs) were recruited on presentation to an emergency department. asthma exacerbation severity was assessed, and respiratory viruses and hrv strains were identified in a nasal aspirate. the majority of ...201120693244
detection of human bocavirus and human metapneumovirus by real-time pcr from patients with respiratory symptoms in southern brazil.the introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hmpv) and human bocavirus (hbov), in respiratory tract specimens. we have studied the occurrence of hmpv and hbov in the porto alegre (pa) metropolitan area, one of the southernmost cities of brazil, evaluating children with suspected lower respiratory tract infection from may 2007-june 2008. a real-time polymerase chain reaction method was used for amplification and de ...201121340356
development of anti-viral agents using molecular modeling and virtual screening techniques.computational chemistry has always played a key role in anti-viral drug development. the challenges and the quickly rising public interest when a virus is becoming a threat has significantly influenced computational drug discovery. the most obvious example is anti-aids research, where hiv protease and reverse transcriptase have triggered enormous efforts in developing and improving computational methods. methods applied to anti-viral research include (i) ligand-based approaches that rely on know ...201121303343
the variable detergent sensitivity of proteases that are utilized for recombinant protein affinity tag removal.recombinant proteins typically include one or more affinity tags to facilitate purification and/or detection. expression constructs with affinity tags often include an engineered protease site for tag removal. like other enzymes, the activities of proteases can be affected by buffer conditions. the buffers used for integral membrane proteins contain detergents, which are required to maintain protein solubility. we examined the detergent sensitivity of six commonly-used proteases (enterokinase, f ...201121539919
hrv signaling in airway epithelial cells is regulated by itam-mediated recruitment and activation of syk.human rhinovirus (hrv), cause of the common cold, is a leading cause of exacerbations of asthma and chronic obstruction pulmonary disease (copd). binding of hrv to icam (intercellular adhesion molecule)-1, its major receptor, induces a profound inflammatory response from airway epithelial cells. my laboratory has identified syk tyrosine kinase to be an early regulator of hrv-icam-1 signalling: syk mediates replication-independent p38 mitogen-activated protein (map) kinase and phosphatidyl-inosit ...201121171946
Detection of human rhinovirus C viral genome in blood among children with severe respiratory infections in the Philippines.Human rhinovirus (HRV) C was recently identified as the third species of HRV using a molecular technique. Infections caused by previously identified HRVs (A and B) are thought to be limited to the respiratory tract; however, pathogenesis of HRVC is still largely unknown. A total of 816 nasopharyngeal swabs from hospitalized children with severe respiratory infections in the Philippines (May 2008-May 2009) were tested for HRV by reverse transcription polymerase chain reaction (RT-PCR), and 243 sa ...201122087272
molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus c.a recently recognized human rhinovirus species c (hrv-c) is associated with up to half of hrv infections in young children. here we propagated two hrv-c isolates ex vivo in organ culture of nasal epithelial cells, sequenced a new c15 isolate and developed the first, to our knowledge, reverse genetics system for hrv-c. using contact points for the known hrv receptors, intercellular adhesion molecule-1 (icam-1) and low-density lipoprotein receptor (ldlr), inter- and intraspecies footprint analyses ...201121483405
clinical spectrum of human rhinovirus infections in hospitalized hong kong children.background:: human rhinovirus (hrv) is classified into a, b, and c genogroups. hrvs cause mild upper respiratory infections, but hrv-c was recently found to be a major cause of asthma exacerbation in whites. this study elucidated disease spectrum of hrv infections among hong kong children hospitalized with respiratory illnesses. methods:: this retrospective study recruited 128 children with asthma exacerbations and 192 inpatient controls without allergy and hospitalized for respiratory illnesses ...201121494174
persistence of rhinovirus rna and ip-10 gene expression after acute asthma.viral nucleic acid may be detected for up to 6 months after an acute asthma deterioration, but the pattern and consequences of viral persistence after acute asthma are incompletely understood. this study investigates the frequency of viral persistence after acute asthma, assesses viral infectivity and determines the host inflammatory responses to viral persistence.201121054674
clinical study concerning the relationship between community-acquired pneumonia and viral infection in northern thailand.objective the etiological agents associated with community-acquired pneumonia (cap) in thailand have been studied extensively in bacterial pathogens, but not in viral pathogens. to clarify the association of viral pathogens with cap, we conducted a comprehensive study of viral and bacterial pathogens in patients with cap. methods we enrolled 119 hospitalized patients with cap in nakornping hospital, chiang mai, thailand between 2006 and 2008. the severity of pneumonia was classified and the risk ...201121532221
Non-invasive sample collection for respiratory virus testing by multiplex PCR.Identifying respiratory pathogens within populations is difficult because invasive sample collection, such as with nasopharyngeal aspirate (NPA), is generally required. PCR technology could allow for non-invasive sampling methods.201121855405
Molecular epidemiological study of human rhinovirus species ABCs from patients with acute respiratory illnesses in Japan.Recent studies suggest that human rhinovirus species A, B, and C (HRV-ABCs) may be associated with both the common cold and severe acute respiratory illnesses (ARI) such as bronchiolitis, wheezy bronchiolitis, and pneumonia. However, the state and molecular epidemiology of these viruses in Japan is not fully understood. We detected the genomes of HRV-ABCs from Japanese patients (92 cases, 0-36 years old, 3.5 ± 5.0 years; mean ± SD) with various ARI including upper respiratory infection (URI), br ...201122016561
[the study of human rhinovirus in infants with lower respiratory tract infections].we want to explore the harm degree of human rhinovirus in infants in beijing area.201121863635
identification of bpr3p0128 as an inhibitor of cap-snatching activities of influenza virus.the aim of this study was to identify the antiviral mechanism of a novel compound, bpr3p0128. from a large-scale screening of a library of small compounds, bpr3p compounds were found to be potent inhibitors of influenza viral replication in madin-darby canine kidney (mdck) cells. bpr3p0128 exhibited inhibitory activity against both influenza a and b. the 50% inhibitory concentrations were in the range of 51-190 nm in mdck cells as measured by inhibition of cytopathic effect assays. bpr3p0128 app ...201121930871
An exercise in molecular epidemiology: human rhinovirus prevalence and genetics.Human rhinovirus (HRV) is one of the most common human respiratory pathogens and is responsible for the majority of upper respiratory illnesses. Recently, a phylogeny was constructed from all known American Type Culture Collection (ATCC) HRV sequences. From this study, three HRV classifications (HRVA, HRVB, and HRVC) were determined and techniques for classifying new isolates of HRV were reported. The genetic change of this virus in specific populations over time is of great interest to understa ...201122081547
severity of human rhinovirus infection in immunocompromised adults is similar to 2009 h1n1 influenza.this retrospective chart review of patients at a tertiary referral center compares characteristics and clinical features of patients diagnosed with human rhinovirus (hrv) to those with 2009 h1n1 influenza a (ph1n1) during the pandemic respiratory season of 2009-2010. hospital admission rates, icu admissions and mortality were not statistically different between the hrv and ph1n1 groups; however, more patients in the hrv group were considered immunocompromised.201122205807
design, synthesis and in vitro evaluation of novel chroman-4-one, chroman, and 2h-chromene derivatives as human rhinovirus capsid-binding inhibitors.as part of an effort to generate broad-spectrum inhibitors of rhinovirus replication, novel series of (e)-3-[(e)-3-phenylallylidene]chroman-4-ones 1a-e, (e)-3-(3-phenylprop-2-yn-1-ylidene)chroman-4-ones 2a and 2b, (z)-3-[(e)-3-phenylallylidene]chromans 3a-e, and (e)-3-(3-phenylprop-1-en-1-yl)-2h-chromenes 4a-d were designed and synthesized. all the compounds were tested in vitro for their efficacy against infection by human rhinovirus (hrv) 1b and 14, two representative serotypes for rhinovirus ...201122088306
human rhinovirus species associated with hospitalizations for acute respiratory illness in young us children.the contribution of human rhinovirus (hrv) to severe acute respiratory illness (ari) is unclear.201122013207
molecular epidemiology of human rhinovirus c in patients with acute respiratory tract infections in osaka city, japan.human rhinovirus (hrv) is a causative agent of acute respiratory tract infection (arti). in 2007, a novel hrv group, hrv-c, was discovered. this study, which assessed whether hrv-c is epidemic among patients with arti, was aimed at analyzing the seasonal prevalence of hrv-c in osaka city, japan. gene amplification tests were performed to detect 10 respiratory viruses in 336 specimens collected during november 2008-october 2009. in total, 364 viruses were detected in 271 specimens. the most ...201122116327
misdirected antibody responses against an n-terminal epitope on human rhinovirus vp1 as explanation for recurrent rv infections.rhinoviruses (rvs) are the primary cause of upper respiratory tract infections, generally known as the common cold. moreover, rv infections can trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (copd). we expressed the 4 major rv capsid proteins, vp1-vp4, in escherichia coli and used these proteins as well as recombinant and synthetic vp1 fragments to study and map antibody responses in rv-infected humans. vp1, which on infection binds to icam 1, was identified as ...201122121050
structural studies on antibody recognition and neutralization of viruses.the purpose of this brief review is to highlight how structural information can elucidate antibody recognition and neutralization of viruses. studies on human rhinovirus demonstrated that antibodies need not induce conformational changes for neutralization and that viruses do not conceal receptor-binding regions from immune recognition. ross river and sindbis virus complexes were an early example of using antibodies to demark receptor-binding regions. the structure of an antibody bound to mouse ...201121887208
spleen tyrosine kinase mediates beas-2b cell migration and proliferation and human rhinovirus-induced expression of vascular endothelial growth factor and interleukin-8.spleen tyrosine kinase (syk) is an immunoregulatory tyrosine kinase that was identified originally in leukocytes. it is a key regulator of innate immunity as well as hematopoietic cell differentiation and proliferation. a role for syk in regulating normal cellular functions in nonhematopoietic cells is increasingly recognized. we have shown previously robust syk expression in airway epithelium, where it regulates the early inflammatory response to human rhinovirus (hrv) infections, and hrv cell ...201122031919
a modern miasma hypothesis and back-to-school asthma exacerbations.a sudden increase in the rate of asthma exacerbations has been observed among young children in many countries 2-3 weeks after their return-to-school following the summer holidays. these exacerbations are frequently associated with human rhinovirus (hrv) infections, with possible interactions with allergen sensitisation, allergen exposure and medication use. it was originally proposed that the sudden increase resulted from new strains of respiratory viruses acquired during the holidays spreading ...201120869177
a novel clustering method via nucleotide-based fourier power spectrum analysis.a novel clustering method is proposed to classify genes or genomes. this method uses a natural representation of genomic data by binary indicator sequences of each nucleotide (adenine (a), cytosine (c), guanine (g), and thymine (t)). afterwards, the discrete fourier transform is applied to these indicator sequences to calculate spectra of the nucleotides. mathematical moments are calculated for each of these spectra to create a multidimensional vector in a euclidean space for each gene or genome ...201121443881
human rhinovirus c--associated severe pneumonia in a neonate.we present a case of severe pneumonia, associated with a prolonged infection by a species c rhinovirus (hrv) in a 3-week old neonate. hrv rna was identified in nasal and nasopharyngeal secretions, bronchoalveolar lavage and bronchial specimens, stool and urine, collected from the patient during a one-month period. no other viral or bacterial agents were detected. sequence analysis of two regions of the viral genome, amplified directly from the clinical specimens revealed a novel hrv-c variant. t ...201121342784
the influence of neonatal lung function on rhinovirus-associated wheeze.several studies have shown that the occurrence of wheezing illnesses during the first year of life is associated with lower levels of lung function shortly after birth and before any respiratory illness. it has been suggested that reduced lung function early in life predisposes infants to wheezing during viral respiratory infections, but the association between neonatal lung function and subsequent confirmed viral infections has never been investigated.201120802166
protein-cation interactions: structural and thermodynamic aspects.cations are specifically recognized by numerous proteins. cations may play a structural role, as cofactors stabilizing their binding partners, or a functional role, as cofactors activating their binding partners or being themselves involved in enzymatic reactions. despite their small size, their charge density and their specific interaction with highly charged residues allow them to induce significant conformational changes on their binding proteins. the protein conformational change induced by ...201121401523
human rhinovirus infection in young african children with acute wheezing.infections caused by human rhinoviruses (hrvs) are important triggers of wheezing in young children. wheezy illness has increasingly been recognised as an important cause of morbidity in african children, but there is little information on the contribution of hrv to this. the aim of this study was to determine the role of hrv as a cause of acute wheezing in south african children.201121401965
Frequent detection of respiratory agents by multiplex PCR on oropharyngeal samples in Swedish school-attending adolescents.Abstract Background: Respiratory agents may be detected in the oropharynx of healthy individuals. The extent of this condition and the reasons behind it are largely unknown. The objective of this study was to determine the factors associated with the presence of respiratory agents in the oropharynx of adolescents healthy enough to attend school activities. Methods: On a single day in December, samples from the posterior wall of the oropharynx of adolescents aged 10-15 y were obtained using cot ...201122103467
[advances in the research of human rhinovirus]. 201121774257
characterization of 2009 h1n1 pandemic influenza in a population of dutch children with influenza-like signs and symptoms.aim: to determine causative respiratory pathogens and describe epidemiological and clinical characteristics in a paediatric population with influenza-like illness during the 2009 h1n1-pandemic. methods: observational study of 412 children visiting an outpatient clinic of a dutch teaching hospital. results: from august to december 2009, 412 children were tested at the clinic; 32% proved h1n1-positive, confirmed by reverse-transcriptase-polymerase-chain-reaction (rt-pcr). pathogens were detecte ...201121767303
effect of lipophilicity modulation on inhibition of human rhinovirus capsid binders.to try and generate broad spectrum human rhinovirus vp1 inhibitors with more attractive physicochemical, dmpk and safety profiles, we explored the current sar of known vp1 compounds. this lead to the identification of specific structural regions where reduction in polarity can be achieved, so guiding chemistry to analogues with significantly superior profiles to previously reported inhibitors.201121907579
development of a quantitative real-time nucleic acid sequence-based amplification assay with an internal control using molecular beacon probes for selective and sensitive detection of human rhinovirus serotypes.evidence demonstrating that human rhinovirus (hrv) disease is not exclusively limited to the upper airways and may cause lower respiratory complications, together with the frequency of hrv infections and the increasing number of immunocompromised patients underline the need for rapid and accurate diagnosis of hrv infections. in this study, we developed the first quantitative real-time nucleic acid sequence-based amplification assay with an internal control using molecular beacon probes for selec ...201121728031
liposomal nanocontainers as models for viral infection: monitoring viral genomic rna transfer through lipid membranes.after uptake into target cells, many nonenveloped viruses undergo conformational changes in the low-ph environment of the endocytic compartment. this results in exposure of amphipathic viral peptides and/or hydrophobic protein domains that are inserted into and either disrupt or perforate the vesicular membranes. the viral nucleic acids thereby gain access to the cytosol and initiate replication. we here demonstrate the in vitro transfer of the single-stranded positive-sense rna genome of human ...201121680510
updates in the relationship between human rhinovirus and asthma.human rhinovirus (hrv) is a nonenveloped, single stranded rna virus belonging to the family picornaviridae. hrv infections can cause both upper and lower respiratory illnesses in children and adults. lower respiratory illnesses are more likely to occur in specific high risk groups, including infants, and children and adults with asthma. the relationships between rates of infection and the risk of clinical illness and exacerbation are not completely understood. recent studies employing polymerase ...201122548203
human rhinovirus recognition in non-immune cells is mediated by toll-like receptors and mda-5, which trigger a synergetic pro-inflammatory immune response.the early detection of invading viruses by the host depends on their identification by pathogen sensors. these include toll-like receptors (tlrs) as well as cytoplasmic rna helicases such as retinoic acid inducible protein i (rig-i) and melanoma differentiation associated gene 5 (mda-5). these pathogen sensors recognize specific molecular patterns found in viruses and trigger inflammatory and antiviral responses that result in the eradication of invading pathogens. in this study we investigated ...201121224721
human rhinovirus in the lower respiratory tract infections of young children and the possible involvement of a secondary respiratory viral agent.human rhinoviruses (hrv) are usually associated with mild respiratory symptoms in children. however, some studies have found that hrv can cause severe disease, especially when the patient is co-infected with a second virus. in this study, 532 nasopharyngeal aspirates (npas) were collected over a nine-year period from children at the clinics hospital of uberlândia. the collected npas were then tested for hrv rna using the reverse transcription-polymerase chain reaction. eighty-three specimens fro ...201121655819
host response cytokine signatures in viral and nonviral acute exacerbations of chronic obstructive pulmonary disease.viruses are strongly associated with acute exacerbations of chronic obstructive pulmonary disease (aecopd). interferon-inducible protein-10 has been recently described as a biomarker of human rhinovirus infection, but there are no reports on the role of other immune mediators in aecopd of viral origin. as an attempt to evaluate the differences in the systemic immune mediators profiles between aecopd patients with presence/absence of viral infection, we measured 27 cytokines, chemokines, and cell ...201121235417
frequency of human rhinovirus species in outpatient children with acute respiratory infections at primary care level in brazil.this study assessed the occurrence of human rhinovirus (hrv) species in outpatient children attending day-care in sao paulo, brazil. hrv reverse transcriptase polymerase chain reaction and amplicon sequencing were done in 120 samples collected in 2008. hrv was detected in 27.5% of samples. hrv c was detected in 60.7% of wheezers, a frequency not different from that observed in nonwheezers (69.6%).201121248656
respiratory virus infections among hospitalized patients with suspected influenza a h1n1 2009 virus during the first pandemic wave in brazil.during the first pandemic wave of the influenza a h1n1 2009 virus, morbidity was particularly high in brazil. hospitalizations resulting from severe respiratory disease due to suspected influenza-like illness created an opportunity to identify other respiratory viruses causing lower respiratory infections.201121670921
ltb4 increases nasal neutrophil activity and conditions neutrophils to exert antiviral effects.leukotriene b4 (ltb4) recruits and activates neutrophils. accordingly, this leukotriene is involved in innate defense actions.201121251805
enterovirus 71 and coxsackievirus a16 3c proteases: binding to rupintrivir and their substrate, and anti-hfmd drug design.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hand foot and mouth disease (hfmd) which is prevalent in asia. thus far there are no prophylactic or therapeutic measures against hfmd. the 3c proteases from ev71 and cva16 play important roles in viral replication and are therefore ideal drug targets. by using biochemical, mutational and structural approaches, we broadly characterized both proteases. a series of high-resolution structures of the free or subst ...201121795339
[molecular epideiological and clinical feature of human metapneumovirus in children with acute respiratory tract infection in nanjing city].to investigate the molecular epideiological and clinical feature of human metapneumovirus in children with acute respiratory tract infection in nanjing city, china.201121789843
[detection and clinical characteristics analysis of human bocavirus 1-3 in children for acute respiratory infection in lanzhou area].to study the clinical and molecular epidemiology characteristics of human bocavirus 1-3 (hbov1-3) in children for acute respiratory infection in lanzhou area.201121789841
entry of a heparan sulphate-binding hrv8 variant strictly depends on dynamin but not on clathrin, caveolin, and flotillin.the major group human rhinovirus type 8 can enter cells via heparan sulphate. when internalized into icam-1 negative rhabdomyosarcoma (rd) cells, hrv8 accumulated in the cells but caused cpe only after 3 days when used at high moi. adaptation by three blind passages alternating between rd and hela cells resulted in variant hrv8v with decreased stability at acidic ph allowing for productive infection in the absence of icam-1. hrv8v produced cpe at 10 times lower moi within 1 day. confocal fluores ...201121262518
host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness.risk factors for severe human rhinovirus (hrv)-associated infant illness are unknown.201121269669
human rhinovirus 2 induces the autophagic pathway and replicates more efficiently in autophagic cells.picornaviruses rearrange cellular membranes to form cytosolic replication sites. in the case of poliovirus and several other picornaviruses, these membranes are derived from subversion of the cellular autophagy pathway. we also reported observation of autophagosome-like structures during infection by two human rhinoviruses, hrv-2 and hrv-14. another group reported that hrv-2 does not induce autophagosomes nor respond to changes in cellular autophagy. here we test hrv-2-infected cells for activat ...201121752910
development of a high-throughput human rhinovirus infectivity cell-based assay for identifying antiviral compounds.asthma and chronic obstructive pulmonary disease exacerbations are associated with human rhinovirus (hrv) lung infections for which there are no current effective antiviral therapies. to date, hrv infectivity of cells in vitro has been measured by a variety of biochemical and immunological methods. this paper describes the development of a high-throughput hrv infectivity assay using hela ohio cells and a chemiluminescent-based atp cell viability system, celltiter-glo from promega, to measure hrv ...201121300110
a large outbreak of hand, foot, and mouth disease caused by ev71 and cav16 in guangdong, china, 2009.a large outbreak of hand, foot and mouth disease (hfmd) occurred in guangdong, china, in 2009. a total of 92,749 cases were officially reported to the center for disease control and prevention of guangdong (gdcdc). to clarify the pathogen causing the outbreak, 600 specimens, including stool, rectal swabs, vesicular swabs, cerebrospinal fluid, and throat swabs, were collected from 541 patients and subjected to one-step rt-pcr. four hundred eighty-nine of 541 patient samples were positive for ente ...201121305327
innate inflammatory responses of pediatric cystic fibrosis airway epithelial cells: effects of nonviral and viral stimulation.there is controversy regarding whether cystic fibrosis (cf) airway epithelial cells (aecs) are intrinsically proinflammatory. the objective of the current study was to characterize the inflammatory profiles of aecs from children with cf compared with cells from healthy control subjects. we obtained aecs from healthy children (12) and children with cf (27). biochemical and functional characteristics were assessed by stimulating cells with ifn?, lps, a cocktail referred to as cytomix, which consis ...201121317379
exogenous ifn-ß has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus.rhinoviruses are the major cause of asthma exacerbations. previous studies suggest that primary bronchial epithelial cells (pbecs) from asthmatic subjects are more susceptible to rhinovirus infection because of deficient ifn-ß production. although augmenting the innate immune response might provide a novel approach for treatment of virus-induced asthma exacerbations, the potential of ifn-ß to modulate antiviral and proinflammatory responses in asthmatic epithelium is poorly characterized.201121329968
viral etiology among the elderly presenting acute respiratory infection during the influenza season.acute respiratory tract infections are the most common illness in all individuals. rhinoviruses have been reported as the etiology of more than 50% of respiratory tract infections worldwide. the study prospectively evaluated 47 elderly individuals from a group of 384 randomly assigned for acute respiratory viral infections (cold or flu) and assessed the occurrence of human rhinovirus (hrv), influenza a and b, respiratory syncytial virus and metapneumovirus (hmpv) in botucatu, state of são paulo, ...201121340401
lower airway rhinovirus burden and the seasonal risk of asthma exacerbation.rationale: most asthma exacerbations are initiated by viral upper respiratory illnesses. it is unclear whether hrv-induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared to hrv colds. objectives: to evaluate viral strain and load in a prospective asthma cohort during a natural cold. methods: adults were enrolled at the first sign of a cold with daily monitoring of symptoms, medication use, and peak expiratory flow rate until resolution. serial ...201121816938
origin of exhaled breath particles from healthy and human rhinovirus-infected subjects.exhaled breath studies suggest that humans exhale fine particles during tidal breathing, but little is known of their physical origin in the respiratory system during health or disease.201121361786
form, symmetry and packing of biomacromolecules. iii. antigenic, receptor and contact binding sites in picornaviruses.the relation between serotype differentiation and crystallographic symmetry, revealed by the contact fingerprint diagrams investigated in part ii [janner (2010). acta cryst. a66, 312-326] for the human rhinovirus, is extended to the picornaviridae family. the approach, outlined in part i [janner (2010). acta cryst. a66, 301-311] and part ii for biomacromolecules packed in a crystal and based on concepts such as packing lattice, kissing points and crystal-packing parameters, can directly be appli ...201121325720
effects of montelukast on patients with asthma after experimental inoculation with human rhinovirus 16.leukotrienes are induced by viral infections.201121354028
human rhinovirus infections in rural thailand: epidemiological evidence for rhinovirus as both pathogen and bystander.we describe human rhinovirus (hrv) detections in sakaeo province, thailand.201121479259
crystal structures of enterovirus 71 3c protease complexed with rupintrivir reveal the roles of the catalytically important residues.ev71 is the primary pathogen causing hfmd, however, the effective antiviral drug is currently unavailable. rupintrivir, an inhibitor against hrv, has potent antiviral activities against ev71. we determined high-resolution crystal structures of ev71 3c(pro)/rupintrivir complex, showing that although rupintrivir interacts with ev71 3c(pro) similarly as with hrv 3c(pro), the c-terminal of the inhibitor cannot accommodate in the leaving group pockets of ev71 3c(pro). our structures reveal that ev71 ...201121813612
an outbreak of human rhinovirus species c infections in a neonatal intensive care unit.we describe an outbreak of human rhinovirus type c infection in 7 infants in our neonatal/pediatric intensive care unit. five infants had clinically significant apneic episodes and 5 required increased oxygen or ventilatory support. infants shed virus detectable by polymerase chain reaction for a median of 4 weeks.201121747322
the effect of a low concentration of hypochlorous acid on rhinovirus infection of nasal epithelial cells.low concentrations of hypochlorous acid (hocl) have been shown to exhibit both antibacterial and anti-influenza virus activity, but hocl still has not been used to kill human rhinovirus (hrv). to model the antiviral effect of nasal irrigation with low-level hocl in patients with the common cold, we tested the effects of a low concentration of hocl on hrv infection of primary human nasal epithelial cells (hnec).201121711976
detection of three human adenovirus species in adults with acute respiratory infection in china.human adenoviruses (hadvs) are recognized as causal agents in a wide range of human diseases. however, researchers lack sufficient data on the exact hadv species and serotypes associated with adult acute respiratory tract infections (artis). to detect and characterize hadv infections in adults in china, clinical specimens were collected from 10,310 adults with artis from may 2005 to july 2010. the partial hadv hexon gene was amplified by polymerase chain reaction (pcr), sequenced, and phylogenet ...201121964587
rhinovirus genome variation during chronic upper and lower respiratory tract infections.routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (hrv) in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. phylogenetic analysis of 144 hrv-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. b ...201121713005
decreased innate immune cytokine responses correlate with disease severity in children with respiratory syncytial virus and human rhinovirus bronchiolitis.the immunopathogenesis of respiratory syncytial virus (rsv) and human rhinovirus lower respiratory tract infections in children remains to be defined. we measured nasal wash concentrations of 29 cytokines in infants with rsv or human rhinovirus lower respiratory tract infections. concentrations of interferon-+¦ in rsv and innate immunity cytokines in both infections inversely correlated with disease severity.201121829141
impact of pollution, climate, and sociodemographic factors on spatiotemporal dynamics of seasonal respiratory viruses.seasonal viruses present a major cause of morbidity and mortality in temperate climates. through major pandemics and smaller annual epidemics, viruses such as influenza, respiratory syncytial virus (rsv) and human rhinovirus (hrv) result in lost school and work days for most that are infected and more serious complications for the immunocompromised. the reasons for these viruses showing strict seasonality include but are not limited to the influence of cold weather and humidity on virus particle ...201121348956
synthesis of 1,4-disubstituted mono and bis-triazolocarbo-acyclonucleoside analogues of 9-(4-hydroxybutyl)guanine by cu(i)-catalyzed click azide-alkyne cycloaddition.a series of novel mono-1,2,3-triazole and bis-1,2,3-triazole acyclonucleoside analogues of 9-(4-hydroxybutyl)guanine was prepared via copper(i)-catalyzed 1,3-dipolar cycloaddition of n-9 propargylpurine, n-1-propargylpyrimidines/as-triazine with the azido-pseudo-sugar 4-azidobutylacetate under solvent-free microwave conditions, followed by treatment with k(2)co(3)/meoh, or nh(3)/meoh. all compounds studied in this work were screened for their antiviral activities [against human rhinovirus (hrv) ...201122202806
engineered picornavirus vpg-rna substrates: analysis of a tyrosyl-rna phosphodiesterase activity.using poliovirus, the prototypic member of picornaviridae, we have further characterized a host cell enzymatic activity found in uninfected cells, termed "unlinkase," that recognizes and cleaves the unique 5' tyrosyl-rna phosphodiester bond found at the 5' end of picornavirus virion rnas. this bond connects vpg, a viral-encoded protein primer essential for rna replication, to the viral rna; it is cleaved from virion rna prior to its engaging in protein synthesis as mrna. due to vpg retention on ...201121408223
adult outpatient experience of the 2009 h1n1 pandemic: clinical course, pathogens, and evaluation of case definitions.the aim was to describe causative agents and clinical characteristics in adult outpatients with upper airway symptoms during the 2009 h1n1 pandemic and to evaluate case definitions that are used in clinical practice.201121420427
viral etiologies of acute respiratory infections among hospitalized vietnamese children in ho chi minh city, 2004-2008.the dominant viral etiologies responsible for acute respiratory infections (aris) are poorly understood, particularly among hospitalized children in resource-limited tropical countries where morbidity and mortality caused by aris are highest. improved etiological insight is needed to improve clinical management and prevention.201121455313
towards the design of combination therapy for the treatment of enterovirus infections.we report here on a comparative study of the activity of 10 enterovirus inhibitors against poliovirus 1, enterovirus 71 and human rhinovirus 14. three of the selected molecules (pleconaril, bta-798 and v-073) are in clinical development. the in vitro antiviral activity of pairwise combinations of inhibitors indicated that most combinations resulted in an additive to slightly synergistic antiviral activity. however, the combination of ribavirin with a nucleoside polymerase inhibitor resulted in a ...201121466823
update on rhinovirus and coronavirus infections.rhinoviruses and coronaviruses cause significant morbidity in immunocompetent people of all ages and in patients with underlying chronic medical or immunosuppressed conditions. newer diagnostic tests, such as polymerase chain reaction (pcr), have expanded our understanding of these respiratory viruses in clinical infections. these sensitive diagnostic tests have been used to describe new members of these virus families, such as human rhinovirus c (hrvc) and human coronavirus nl-63 (hcov-nl63). t ...201121858748
therapeutic strategies to reduce asthma exacerbations.asthma exacerbations can occur in patients with all degrees of asthma severity. they generally develop over 5 to 7 days and are most often initiated by an upper respiratory tract infection (usually with human rhinovirus) or by environmental allergen exposure in atopic subjects. inhaled corticosteroids (icss) taken on a regular basis are very effective in reducing the risk of asthma exacerbations, and the combination of icss and long-acting inhaled β(2)-agonists further reduces this risk. in addi ...201121531015
rhinovirus-induced bronchiolitis and asthma development.to cite this article: jartti t, korppi m. rhinovirus-induced bronchiolitis and asthma development. pediatr allergy immunol 2011; 22: 350-355. abstract: human rhinovirus (hrv) and respiratory syncytial virus (rsv) are commonly associated with bronchiolitis. the breaking point in the dominance is approximately 12 months - rhinovirus dominates in the older children. predisposition may markedly increase the prevalence of hrv bronchiolitis. especially, low interferon responses and atopy-related facto ...201121535176
detection of ki polyomavirus and wu polyomavirus dna by real-time pcr in nasopharyngeal swabs and in normal lung and lung adenocarcinoma tissues.polyomaviruses ki (kipyv) and wu (wupyv) were detected from 7 (3.0%) and 38 (16.4%) of 232 children with respiratory tract infections by real-time pcr. the rates of single infection of kipyv and wupyv were 3 (42.9%) of 7 and 20 (52.6%) of 38, respectively. in other samples, various viruses (human respiratory syncytial virus, human metapneumovirus (hmpv), human rhinovirus, parainfluenza virus 1 and human bocavirus) were detected simultaneously. one case was positive for kipyv and wupyv and also f ...201121545509
Highly frequent infections with human rhinovirus in healthy young children: a longitudinal cohort study.Human rhinoviruses (HRVs) are an important cause of respiratory tract infections.201121982210
a host-specific, temperature sensitive translation defect determines the attenuation phenotype of a human rhinovirus/poliovirus chimera pv1(ripo).using pv1(ripo), a chimeric poliovirus, utilizing the cognate ires of human rhinovirus type 2 (hrv2), we set out to shed light on the mechanism by which this variant expresses its attenuated phenotype in poliovirus-sensitive, cd155 transgenic (tg) mice and cynomolgus monkeys. here we report that replication of pv1(ripo) is restricted not only in human cells of neuronal origin, as was reported previously, but also in cells of murine origin at physiological temperature. this block in replication w ...201121561914
a molecular epidemiological study of respiratory viruses detected in japanese children with acute wheezing illness.recent studies strongly suggest that some respiratory viruses are associated with the induction of acute wheezing and/or exacerbation of bronchial asthma. however, molecular epidemiology of these viruses is not exactly known.201121663657
homology modeling, docking, molecular dynamics simulation, and structural analyses of coxsakievirus b3 2a protease: an enzyme involved in the pathogenesis of inflammatory myocarditis.2a protease of the pathogenic coxsackievirus b3 is key to the pathogenesis of inflammatory myocarditis and, therefore, an attractive drug target. however lack of a crystal structure impedes design of inhibitors. here we predict 3d structure of cvb3 2a(pro) based on sequence comparison and homology modeling with human rhinovirus 2a(pro). the two enzymes are remarkably similar in their core regions. however they have different conformations at the n-terminal. a large number of n-terminal hydrophob ...201121664926
[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
[a gexp based multiplex rt-pcr assay for simultaneous detection of twelve human respiratory viruses].a gexp based multiplex rt-pcr assay was developed to simultaneously detect twelve different respiratory viruses types/subtypes including influenza a virus, influenza b virus, influenza a virus sh1n1, parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3, human rhinovirus, human metapneumovirus, adenovirus, respiratory syncytial virus a, respiratory syncytial virus b and human bocavirus. twelve sets of specific primers were designed based on the conserved sequences of ...201122263264
Negative Control of TLR3 Signaling by TICAM1 Downregulation.Toll-IL-1 receptor (TIR) domain-containing adaptor molecule-1 (TICAM1, also called TRIF) is an important adaptor protein in TLR3 and TLR4 signaling pathways to mediate proinflammatory cytokine and interferon responses. Negative regulations of TICAM1 by either exogenous viral protease or endogenous caspase and proteasome, have been reported to shut down the TICAM1-mediated signaling. In this report, we have discovered that the downregulation of TICAM1, but not other components in this signaling p ...201122205631
Evidence for a Causal Relationship Between Allergic Sensitization and Rhinovirus Wheezing in Early Life.RATIONALE: Both aeroallergen sensitization and virus-induced wheezing are risk factors for asthma development during early childhood, but the temporal developmental sequence between them is incompletely understood. OBJECTIVE: To define the developmental relationship between aeroallergen sensitization and virus-induced wheezing. METHODS: A total of 285 children at high-risk for allergic disease and asthma were followed prospectively from birth. The timing and etiology of viral respiratory wh ...201121960534
[three years surveillance of viral etiology of acute lower respiratory tract infection in children from 2007 to 2010].viruses are common pathogens of acute lower respiratory tract infection (alrti) in children. there are few studies on consecutive monitoring of viral pathogens of alrti in a larger cohort during the past several years. the aim of this study was to investigate the viral pathogens of alrti in children of different age groups and to outline the epidemic feature of different viruses.201122321179
microscopic symmetry imposed by rotational symmetry boundary conditions in molecular dynamics simulation.a large number of viral capsids, as well as other macromolecular assemblies, have icosahedral structure or structures with other rotational symmetries. this symmetry can be exploited during molecular dynamics (md) to model in effect the full viral capsid using only a subset of primary atoms plus copies of image atoms generated from rotational symmetry boundary conditions (rsbc). a pure rotational symmetry operation results in both primary and image atoms at short range, and within nonbonded inte ...201122096451
production and single-step purification of egfp and a biotinylated version of the human rhinovirus 14 3c protease.the fluorescent reporter enhanced green fluorescent protein (egfp) has been used for assaying a wide range of biological activities ranging from gene expression, or localization of target proteins through to intermolecular interactions. however, over-production of this protein in escherichia coli has resulted in the presence of inclusion bodies, which complicates recovery of the protein in significant quantities. in this paper, we describe a single-step method for isolating the protein from a gl ...201121605680
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
respiratory viruses in hospitalized children with influenza-like illness during the h1n1 2009 pandemic in sweden.the swine-origin influenza a(h1n1)pdm09 pandemic of 2009 had a slower spread in europe than expected. the human rhinovirus (hrv) has been suggested to have delayed the pandemic through viral interference. the importance of co-infections over time during the pandemic and in terms of severity of the disease needs to be assessed.201223272110
high detection frequency and viral loads of human rhinovirus species a to c in fecal samples; diagnostic and clinical implications.human rhinoviruses (hrvs) can be divided into three species; hrv-a to hrv-c. up to 148 different hrv (sero)types have been identified to date. because of sequence similarity between 5'-ncr of hrvs and enteroviruses (evs), it is problematic to design ev-specific rt-pcr assays. the aims of this study were to assess the rate of false-detection of different rhinoviruses by ev rt-pcr, and to evaluate the diagnostic and clinical significance of such cross-reactivity. in vitro rna transcripts of hrv a- ...201222246843
the 3a protein from multiple picornaviruses utilizes the golgi adaptor protein acbd3 to recruit pi4kiiiβthe activity of phosphatidylinositol 4-kinase class iii beta (pi4kiiiβ) has been shown to be required for the replication of multiple picornaviruses, however it is unclear whether a physical association between pi4kiiiβ and the viral replication machinery exists and if it does, whether association is necessary. we examined the ability of the 3a protein from 18 different picornaviruses to form a complex with pi4kiiiβ by affinity purification of strep-tagged transiently transfected constructs foll ...201222258260
[detection and clinical features of human rhinovirus in hospitalized children with acute respiratory tract infection in eastern areas of guangdong province].to investigate the prevalence and clinical features of human rhinovirus (hrv) infection in hospitalized children with acute respiratory (ari) in eastern areas of guangdong province from 2008 to 2010.201223290856
Ex Vivo and In Vivo Inhibition of Human Rhinovirus Replication by a New Pseudosubstrate of Viral 2A Protease.Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A(pro)) and inhibited its activity. This peptide was chemically modified with a reactiv ...201222072773
seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay.abstract background: nucleic acid amplification tests are increasingly being used to diagnose viral and bacterial respiratory tract infections. the high sensitivity of these tests affects our understanding of the epidemiology of respiratory tract infections. we have assessed the detection rate of a multiplex real-time polymerase chain reaction (pcr) test, with emphasis on epidemiology and seasonal distribution of the most common respiratory tract infections. methods: seven thousand eight hundr ...201221867470
Modification of the untranslated regions of human enterovirus 71 impairs growth in a cell-specific manner.Human enterovirus 71 (HEV71) is the causative agent of hand, foot, and mouth disease and associated acute neurological disease. At present, little is known about the genetic determinants of HEV71 neurovirulence. Studies of related enteroviruses have indicated that the untranslated regions (UTRs), which control virus-directed translation and replication, also exert significant influence on neurovirulence. We used an infectious cDNA clone of a subgenogroup B3 strain to construct and characterize c ...201222031931
Experimental human rhinovirus and enterovirus interspecies recombination.Human rhinoviruses (HRVs) and enteroviruses (HEVs), two important human pathogens, are non-enveloped, positive-sense RNA viruses of the genus Enterovirus within the family Picornaviridae. Intraspecies recombination is known as a driving force for enterovirus and, to a lesser extent, rhinovirus evolution. Interspecies recombination is much less frequent among circulating strains, and supporting evidence for such recombination is limited to ancestral events, as shown by recent phylogenetic analyse ...201221940413
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