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[human enterovirus 71 (ev71) resisted type i interferon induced antiviral effect].to investigate human enterovirus 71 (ev71) resistance to type i interferon induced antiviral effect.201223002545
diagnosis of hand, foot, and mouth disease caused by ev71 and other enteroviruses by a one-step, single tube, duplex rt-pcr.hand, foot, and mouth disease (hfmd) is caused mainly by enterovirus 71 (ev71) and other enteroviruses (evs) such as coxsackie a16 in china. ev71 infection can lead to severe clinical manifestations and even death. other evs, however, generally cause mild symptoms. thus, early and accurate distinction of ev71 from other evs for hfmd will offer significant benefits. a one-step, single tube, duplex rt-pcr assay is described in the present study to detect simultaneously ev71 and other evs. the prim ...201222997084
excessive proinflammatory cytokine and chemokine responses of human monocyte-derived macrophages to enterovirus 71 infection.the levels of proinflammatory cytokine or chemokine in blood and cerebrospinal fluid are thought to be one of predictors for clinical severity of enterovirus 71 (ev71) infection, yet the cellular sources or signalling mechanism remain undefined. here, we focused on the response of human primary monocyte-derived macrophages (mdms) to ev71 virus and its possible mechanisms.201222994237
infectious disease experts monitor outbreaks of enterovirus 71 in asia. 201222988146
population dynamics and genetic diversity of c4 strains of human enterovirus 71 in mainland china, 1998-2010.since 1997, several countries within the asian pacific region have been affected by one or more massive outbreaks of hand foot and mouth disease (hfmd). virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (ev71) belonging to several different, recently emerged subgenogroups. in mainland china, a different situation was observed. the first outbreak, localized in shangdong province, was reported in 2007, and was followed by a wide-spread outbreak i ...201222984501
[expression of structural protein vp1 of enterovirus 71 in e.coli and preparation of anti-vp1 monoclonal antibodies].to express recombinant structural protein vp1 of enterovirus 71 (ev71) in e.coli and prepare anti-vp1 monoclonal antibodies (mabs).201222980661
[a case-control study on risk factors that associated with severe hand-foot-mouth disease in shanghai].to explore the factors associated with severe hand-food-mouth disease (hfmd) case in shanghai.201222967324
antiviral protection against enterovirus 71 mediated by autophagy induction following flice-inhibitory protein inactivation.even with the recent awareness of enterovirus 71 (ev71) as a major public health issue, there are no preventive or therapeutic agents that are effective against ev71 infection. although flice-like inhibitory protein (flip) has been identified as a factor that modulates virus pathogenesis, there are no reports regarding its effects on ev71 infection. the aim of the present study was to identify whether flip influences ev71 pathogenesis and to understand the underlying mechanisms. virus replicatio ...201222960766
cytokine immunopathogenesis of enterovirus 71 brain stem encephalitis.enterovirus 71 (ev71) is one of the most important causes of herpangina and hand, foot, and mouth disease. it can also cause severe complications of the central nervous system (cns). brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. ev71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. cyto ...201222956971
structure determination of enterovirus 71.enterovirus 71 is a picornavirus that causes hand, foot and mouth disease but may induce fatal neurological illness in infants and young children. enterovirus 71 crystallized in a body-centered orthorhombic space group with two particles in general orientations in the crystallographic asymmetric unit. determination of the particle orientations required that the locked rotation function excluded the twofold symmetry axes from the set of icosahedral symmetry operators. this avoided the occurrence ...201222948923
[neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease : clinical features, mri findings and follow-up study].to explore the clinical and magnetic resonance imaging (mri) characteristics and the follow-up outcomes of neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease.201222944180
antiviral effect of matrine against human enterovirus 71.human enterovirus 71, a member of the picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. this illness has caused mortalities in large-scale outbreaks in the asia-pacific region in recent years. no vaccine or antiviral therapy is available. in this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. matrine could suppress the viral rna copy number on rhabdomyosarcoma cells. more ...201222932217
reactogenicity and immunogenicity of an enterovirus 71 vaccine in chinese healthy children and infants.enterovirus 71 (ev71) is highly contagious and can cause severe complications. a safe and effective vaccine is needed. we assessed the reactogenicity and immunogenicity of an inactivated, alum-adjuvanted ev71 vaccine in this study.201222926209
identification of site-specific adaptations conferring increased neural cell tropism during human enterovirus 71 infection.enterovirus 71 (ev71) is one of the most virulent enteroviruses, but the specific molecular features that enhance its ability to disseminate in humans remain unknown. we analyzed the genomic features of ev71 in an immunocompromised host with disseminated disease according to the different sites of infection. comparison of five full-length genomes sequenced directly from respiratory, gastrointestinal, nervous system, and blood specimens revealed three nucleotide changes that occurred within a fiv ...201222910880
development of a dot-immunoenzyme filtration assay for the detection of enterovirus 71 antigen in human serum via immunoglobulin m.this study evaluated the sensitivity and specificity of a rapid, sensitive dot-immunoenzyme filtration assay to detect enterovirus 71 (ev71) antigen in serum samples from paediatric patients with hand, foot and mouth disease (hfmd), through detection of anti-ev71 immunoglobulin (ig)m.201222906286
expression and purification of enterovirus type 71 polyprotein p1 using pichia pastoris system.enterovirus type 71(ev71) causes severe hand-foot-and-mouth disease (hfmd) resulting in hundreds of deaths of children every year; however, currently, there is no effective treatment for ev71. in this study, the ev71 poly-protein (ev71-p1 protein) gene was processed and cloned into the eukaryotic expression vector ppic9k and then expressed in pichia pastoris strain gs115. the ev71 p1 protein with a molecular weight of 100 kd was produced and secreted into the medium. the soluble ev71 p1 protein ...201222899434
the highly conserved 5' untranslated region as an effective target towards the inhibition of enterovirus 71 replication by unmodified and appropriate 2'-modified sirnas.enterovirus 71 (ev71) is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. it is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. currently, no effective vaccine or specific clinical therapy is available against ev71.201222889374
immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters.enterovirus 71 (ev71) causes severe neurological diseases resulting in high mortality in young children worldwide. development of an effective vaccine against ev71 infection is hampered by the lack of appropriate animal models for efficacy testing of candidate vaccines. previously, we have successfully tested the immunogenicity and protectiveness of a candidate ev71 vaccine, containing recombinant newcastle disease virus capsids that display an ev71 vp1 fragment (npt-vp11-100) protein, in a mous ...201222877087
blocking human enterovirus 71 replication by targeting viral 2a protease.human enterovirus 71 (ev-71), a member of the enterovirus genus, constitutes a major public health issue in the asia-pacific region, where it is associated with several severe neurological complications. there is currently no effective vaccine or antiviral against ev-71. the aim of this study was to determine whether the six amino acid peptide lvlqtm, which was previously shown to inhibit human rhinovirus (hrv) 2a protease (2a(pro)) activity in vitro and hrv replication in vivo in mice, could be ...201222865380
[construction, expression and immunogenicity of ev71 multiepitope-mgitrl eukaryotic plasmid].to construct an enterovirus 71(ev71) multiepitope-mgitrl eukaryotic plasmid and study its immunogenicity in balb/c mice.201222863582
cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells.enterovirus 71 (ev71) is a major causative agent of hand-foot-and-mouth disease (hfmd), and infection of ev71 to central nerve system (cns) may result in a high mortality in children less than 2 years old. although there are two highly glycosylated membrane proteins, scarb2 and psgl-1, which have been identified as the cellular and functional receptors of ev71, the role of glycosylation in ev71 infection is still unclear.201222853823
protection against enterovirus 71 with neutralizing epitope incorporation within adenovirus type 3 hexon.enterovirus 71 (ev71) is responsible for hand, foot and mouth disease with high mortality among children. various neutralizing b cell epitopes of ev71 have been identified as potential vaccine candidates. capsid-incorporation of antigens into adenovirus (ad) has been developed for a novel vaccine approach. we constructed ad3-based ev71 vaccine vectors by incorporating a neutralizing epitope sp70 containing 15 amino acids derived from capsid protein vp1 of ev71 within the different surface-expose ...201222848478
in enterovirus 71 encephalitis with cardio-respiratory compromise, elevated interleukin 1β, interleukin 1 receptor antagonist, and granulocyte colony-stimulating factor levels are markers of poor prognosis.enterovirus 71 (ev71) causes large outbreaks of hand, foot, and mouth disease (hfmd), with severe neurological complications and cardio-respiratory compromise, but the pathogenesis is poorly understood.201222829643
clinicopathologic features and molecular analysis of enterovirus 71 infection: report of an autopsy case from the epidemic of hand, foot and mouth disease in china.a 15-month boy with fatal hand, foot, and mouth disease (hfmd) exhibited atypical symptoms and progressed rapidly to death. an autopsy was performed the next day and tissue sections were stained for histopathological examination. his intestinal samples were tested for enterovirus 71 (ev71), and the whole-genome sequence of ev71 was analyzed. an autopsy revealed that the central nervous system, lungs, and gut displayed severe meningitis and brainstem encephalitis, remarkable pulmonary congestion, ...201222827767
the effect of enterovirus 71 immunization on neuropathogenesis and protein expression profiles in the thalamus of infected rhesus neonates.enterovirus 71 (ev71) is a major pathogen that causes hand-foot-mouth disease (hfmd). our previous studies have demonstrated that the complete process of pathogenesis, which may include tissue damage induced by host inflammatory responses and direct tissue damage caused by viral infection, can be observed in the central nervous system (cns) of animals infected in the laboratory with ev71. based on these observations, the neuropathogenesis and protein expression profiles in the thalamic tissues o ...201222819834
selection and characterisation of guanidine-resistant mutants of human enterovirus 71.the replication of human enterovirus 71 (hev71) in cell culture is inhibited by concentrations of guanidine that do not have an observable adverse effect on host cell metabolism. although the hev71 non-structural protein 2c is known to play an important role in viral rna replication, its precise biochemical activities and structure have not been fully determined. here we describe amino acid substitutions in hev71 protein 2c that confer resistance to guanidine. three guanidine-resistant virus pop ...201222814431
[progress in research on acute pulmonary edema caused by enterovirus 71]. 201222801228
[evolution and prognosis of the acute flaccid paralysis associated with enterovirus 71 infection evaluated through a clinical and magnetic resonance imaging follow-up study].to explore the development and prognosis of the acute flaccid paralysis (afp) associated with enterovirus 71 (ev71) infection through clinical follow-up study for clinical and magnetic resonance imaging (mri) features based on the research progress of virology and pathology.201222801224
[evaluation of adrenocortical function in children with severe and critical enterovirus 71 infection].to evaluate the adrenocortical function in children with severe and critical enterovirus 71 infection by using a high-dose (250 µg) adrenocorticotropic hormone (acth) stimulation test. and to at provide experimental basis for glucocorticoid in the treatment of hand-foot-and-mouth disease (hfmd).201222801223
[thinking about the intervention strategy for critically ill hand-foot-and-mouth disease caused by enterovirus 71 infection]. 201222801222
development of murine monoclonal antibodies with potent neutralization effects on enterovirus 71.enterovirus 71 (ev71) is a member of the picornaviridae family and one of the main causative agents of hand, foot, and mouth disease (hfmd). currently, ev71 infection is prevalent in the asia-pacific regions where it affects millions of children under the age of five, causing significant morbidity and mortality. no specific vaccine or antiviral drugs are available for ev71. the development of murine monoclonal antibodies (mabs) with potent neutralization effects on ev71 is described. mab-secreti ...201222771741
in vitro evaluation of the antiviral activity of heparan sulfate mimetic compounds against enterovirus 71.enterovirus 71 (ev71) is the causative agent of hand foot and mouth disease (hfmd) and can also cause fatal neurological complications for which currently there is no vaccine or approved antiviral drug. despite suggestions that heparan sulfate (hs)-like compounds are effective antivirals against various viruses, no research has been undertaken to examine their effects upon ev71. therefore, this study aimed to investigate the in vitro anti-ev71 effect of hs mimetics (heparin, heparan sulfate, and ...201222771616
[the assemblage, purification and characterization of ev71 vlps expressed in baculovirus].to construct a recombinant expression plasmid bacmid-p1-3cd containing the p1 and 3cd genes of enterovirus 71(ev71), the p1 and 3cd genes were cloned into the same baculovirus shuttle vector (bacmid). recombinant acmnpv-p1-3cd was obtained by transfecting the bacmid-p1-3cd into the insect cell line of s f9. with the ifa and western-blot methods for identification of expression products confirmed that the target protein was expressed in interior of infected s f9 cells. electron microscopy showed ...201222764520
[expression and activity analysis of enterovirus 71 3c protease in escherichia coli].the recombinant plasmid carrying the gene encoding 3c protease of enterovirus 71 (ev71) was constructed, the recombinant protein was then expressed and purified, the functional activity was also measured. firstly, the 3c protease gene was inserted into pet28a vector, the constructed recombinant plasmid was transformed into e. coli bl21 (de3) for expression under the induction of iptg. the expressed protein was purified by affinity chromatography (ni-nta) and the n-terminus his-tag was cleaved by ...201222764519
[chest x-ray findings in children with enterovirus 71 infection].to study the characteristics of the chest x-ray images in children infected with enterovirus 71.201222738450
continuous veno-venous hemofiltration for treatment of enterovirus 71-induced fulminant cardiopulmonary failure: a case report.fulminant cardiopulmonary failure is a severe complication of hand, foot and mouth diseases due to enterovirus 71 infection, with a high mortality rate. the treatment is mainly supportive with aggressive cardiopulmonary resuscitation. we report the use of continuous veno-venous hemofiltration in a patient with pulmonary edema and shock due to enterovirus 71 infection. to the best of our knowledge, this is the first report of the use of continuous veno-venous hemofiltration to successfully treat ...201222734721
display of enterovirus 71 vp1 on baculovirus as a type ii transmembrane protein elicits protective b and t cell responses in immunized mice.human enterovirus 71 (ev71) has become a major public health threat across asia pacific. the virus causes hand, foot, and mouth disease which can lead to neurological complications in young children. there are no specific antivirals or vaccines against ev71 infection. the major neutralizing epitope of ev71 is located in the carboxy-terminal half of the vp1 protein at amino acid positions 215-219 (lim et al., 2012). to study the immunogenicity of vp1 we have developed a baculovirus vector which d ...201222728446
[morphological changes of brain choroid plexuses and ventricle induced by enterovirus infections in monkeys].the morphological study of monkeys' brains, infected by the bulgaria strain of enterovirus-71 (ev71), revealed specific for truncus cerebral encephalomyelitis, reactive and destructive changes in different areas of the brainstem and the spinal cord. for the first time viral cytopathology and destruction of choroid plexuses as an important secretory organ of the central nervous system, and ventricle of the brain infected by enterovirus have been studied. the specificity of this infection and the ...201222712308
induction of protective immune responses against ev71 in mice by baculovirus encoding a novel expression cassette for capsid protein vp1.ev71 is a major causative agent of hand, foot and mouth disease (hfmd) and is responsible for large outbreaks in various asian pacific countries. in the present study, we generated the recombinant baculovirus (bac-vp1) encoding vp1 in a novel expression cassette. the transmembrane domain of hemagglutinin of the h3n2 influenza virus was included in the cassette as a minimal membrane anchor for vp1. the protective immunity of bac-vp1 was investigated in a mouse model. the results showed that mice ...201222691220
a single mutation in capsid protein vp1 (q145e) of a genogroup c4 strain of human enterovirus 71 generates a mouse-virulent phenotype.we modified the capsid protein of a human enterovirus 71 (hev71) belonging to subgenogroup c4 (hev71-c4) to generate a mouse virulent strain, based on the genetic information derived from our previous subgenogroup b3 mouse-adapted virus. infectious clone-derived mutant virus populations containing the capsid protein mutations vp1-q145e and vp1-q145g were generated by site-directed mutagenesis of an infectious clone of a subgenogroup c4 strain. viruses expressing the vp1-q145e were virulent in 5- ...201222647370
prevention of human enterovirus 71 infection by kappa carrageenan.enterovirus 71 (ev 71), the newest member of enteroviridae, is notorious for its etiological role in epidemics of the hand-foot-and-mouth disease, particularly in association with fatal neurological complications in young children. searching for new and more effective agents against ev 71 infections has never relented as corresponding vaccines or antiviral drugs remain unavailable. sulfated polysaccharides from seaweed are known to possess a broad range of biological activities across anti-virus ...201222643729
the pathogenesis and prevention of encephalitis due to human enterovirus 71.human enterovirus 71 (hev71) has emerged as a major cause of viral encephalitis in southeast asia, with increased epidemic activity observed since 1997. this is reflected in a large increase in scientific publications relating directly to hev71. new research is elucidating details of the viral life cycle, confirming similarities between hev71 and other enteroviruses. scavenger receptor b2 (scarb2) is a receptor for hev71, although other receptors are likely to be identified. currently, the only ...201222639066
tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in chinese healthy adults and children: an open label, phase 1 clinical trial.in this open labeled phase 1 clinical trial with enterovirus 71 (ev71) vaccine (clinicaltrials.gov number: nct01267903) performed in donghai county, jiangsu province, china, in january 2011. a total of 100 healthy participants, stratified by age (40 adults aged 16-22 y and 60 children aged 6-15 y), were enrolled from volunteers and sequentially received ev71 vaccines of 160u (only for children), 320u, or 640u on day 0 and 28, in a manner of dose escalation. all the participants were followed for ...201222634437
[distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].to explore the mechanism that how human enterovirus 71 (ev71) invades the brainstem and how intercellular adhesion molecules-1 (icam-1) participates by analyzing the expression and distribution of human ev71, and icam-1 in brainstem of infants with brain stem encephalitis.201222619799
clinical characteristics of hand, foot and mouth disease in harbin and the prediction of severe cases.hand, foot and mouth disease (hfmd) is an emerging public health problem in china, not only threatening the health of children, but also causing tremendous loss and burden to both families and society. the aim of this study was to characterize the epidemiology and clinical features of hfmd, and to understand the key factors affecting hfmd in the harbin region to provide scientific evidence for effective prevention and control strategies.201222613598
daphne genkwa sieb. et zucc. water-soluble extracts act on enterovirus 71 by inhibiting viral entry.dried flowers of daphne genkwa sieb. et zucc. (thymelaeaceae) are a chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. however, the activity of this medicine against enteroviral infections has not been investigated. the water-extract of dried buds of d. genkwa sieb. et zucc. (dgfw) was examined against various strains of enterovirus 71 (ev71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assa ...201222590685
linear normalised hash function for clustering gene sequences and identifying reference sequences from multiple sequence alignments.comparative genomics has put additional demands on the assessment of similarity between sequences and their clustering as means for classification. however, defining the optimal number of clusters, cluster density and boundaries for sets of potentially related sequences of genes with variable degrees of polymorphism remains a significant challenge. the aim of this study was to develop a method that would identify the cluster centroids and the optimal number of clusters for a given sensitivity le ...201222587938
molecular epidemiology and evolution of human enterovirus serotype 68 in thailand, 2006-2011.publications worldwide have reported on the re-occurrence of human enterovirus 68 (ev68), a rarely detected pathogen usually causing respiratory illness. however, epidemiological data regarding this virus in particular on the asian continent has so far been limited.201222586446
analysis of the th1/th2 reaction in the immune response induced by ev71 inactivated vaccine in neonatal rhesus monkeys.although clinical trials for the enterovirus type 71 (ev71) inactivated vaccine have been progressing, the potential mechanism of ev71 infection and its associated pathogenesis are not well-characterized in terms of comprehensive analysis of the induced immune response, which is generally recognized as an important indicator of the safety of vaccines. to investigate the th1/th2 response following viral challenge in neonatal rhesus monkeys immunized with different doses of ev71 inactivated vaccin ...201222585051
paroxysmal supraventricular tachycardia in an infant with hand, foot, and mouth disease.an 11-month-old male infant was admitted to our hospital with fever, fussiness, poor feeding, vomiting, and tachypnea for two days prior. physical examination revealed sporadic papules and vesicles occurring on his hands, feet, face, and perianal mucosa. enterovirus 71 was identified from both throat swab and vesicle fluid using virus isolation techniques. the patient's heart rate fluctuated in a very narrow range from 180~210/beats/min regardless of his physiologic state. an electrocardiogram s ...201222577272
mouse adaptation of a sub-genogroup b5 strain of human enterovirus 71 is associated with a novel lysine to glutamic acid substitution at position 244 in protein vp1.most human enterovirus 71 (hev71) strains infect only primates and are unable to cause clinically apparent infection in mice. here we describe a mouse-adapted hev71 strain that belongs to sub-genogroup b5 with increased virulence in newborn balb/c mice. the mouse-virulent strain was initially selected by serial passage of a hev71 clinical isolate (hev71-b5) in chinese hamster ovary (cho) cells (cho-b5), followed by serial passage in newborn mice. virus from the fifth mouse passage was cultured t ...201222575826
[survey on the recessive infection of pathogen to hand-foot-mouth disease among healthy adults and children in guangdong province].to understand the pathogen-carrying status of hand-foot-mouth disease (hfmd) among healthy people in guangdong province.201222575141
a case-control study of risk factors for severe hand-foot-mouth disease among children in ningbo, china, 2010-2011.a small fraction of hand-foot-mouth disease (hfmd) progression from the onset of severity to fatality may be remarkably rapid. early recognition of children at risk of severity is critical to increase treatment effectiveness and reduce acute mortality.201222527564
[complete genome sequence characteristics of human enterovirus 71 strain isolated in yunnan, china].the complete nucleotide sequence of two human enterovirus 71 strains (kmm09 and km186-09) isolated in yunnan,china, were determined by rt-pcr and sequencing. as with other human enteroviruses, the genomes were 7 409 nucleotides (nts) in length and encoded 2 193 aa. phylogenetic analysis based on vp1 regions revealed that the two isolates belonged to subgenotype c4a. in structural genomic regions, subgenotype c4 was most homologous to other strains of c genotype when compared to other genotypes. ...201222519170
genetic characterization of enterovirus 71 isolated from patients with severe disease by comparative analysis of complete genomes.enterovirus 71 (ev71) which causes mild illness in children is also associated with severe neurological complications. this study analyzed the complete genomes of ev71 strains derived from mild and severe diseases in order to determine whether the differences of ev71 genomes were responsible for different clinical presentations. compared to complete genomes of ev71 strains derived from mild cases (less virulent strains), nucleotide differences in ev71 strains isolated from severe cases (more vir ...201222499017
extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis: long-term neurologic follow-up.enterovirus 71 rhombencephalomyelitis with cardiopulmonary dysfunction has become an endemic problem in taiwan since an epidemic outbreak in 1998. such cases frequently involve significant morbidity and mortality. from october 2000-june 2008, we collected 10 consecutive patients diagnosed with enterovirus 71 rhombencephalomyelitis complicated by left heart failure, with or without pulmonary edema, and surviving more than 3 months after receiving extracorporeal life support. follow-up neurologic ...201222490767
encephalitis due to emerging viruses: cns innate immunity and potential therapeutic targets.the emerging viruses represent a group of pathogens that are intimately connected to a diverse range of animal vectors. the recent escalation of air travel climate change and urbanization has meant humans will have increased risk of contacting these pathogens resulting in serious cns infections. many rna viruses enter the cns by evading the bbb due to axonal transport from the periphery. the systemic adaptive and cns innate immune systems express pattern recognition receptors prr (tlrs, rig-1 an ...201222484271
recent advances in the molecular epidemiology and control of human enterovirus 71 infection.human enterovirus 71 (hev71) has emerged as an important cause of viral encephalitis in the southeast asia over the past 15 years. a pattern of increased epidemic activity and endemic circulation of hev71 has been observed since 1997 and is associated with the regular emergence of new genetic lineages. although the reason for this increase in hev71 circulation remains unknown, evidence is accumulating that recombination events may drive the evolution of new genetic lineages. prevention of hev71 ...201222482716
characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern china.human enterovirus 71 (ev71)-associated hand, foot, and mouth disease (hfmd) has been a leading cause of childhood infection in china since 2008. epidemic and molecular characteristics of hfmd have been examined in many areas of china, including the central and southern regions. however, clinical and genetic characterization of ev71 in the northeastern region of china is scarce. in this study, a series of analyses were performed on seven full-length ev71 sequences from hfmd patients who had eithe ...201222479324
a 3d framework for understanding enterovirus 71.two papers report the structure of the virion of emerging pathogen ev71, providing a three-dimensional context for understanding many of its biological functions.201222472617
inhibition of enterovirus 71 entry by transcription factor xbp1.inositol-requiring enzyme 1 (ire1) plays an important role in the endoplasmic reticulum (er), or unfolded protein, stress response by activating its downstream transcription factor x-box-binding protein 1 (xbp1). we demonstrated previously that enterovirus 71 (ev71) upregulated xbp1 mrna levels but did not activate spliced xbp1 (xbp1s) mrna or its downstream target genes, edem and chaperones. in this study, we investigated further this regulatory mechanism and found that ire1 was phosphorylated ...201222469468
fisetin and rutin as 3c protease inhibitors of enterovirus a71.enterovirus a71 (ev-a71) causes severe complications: encephalitis, pulmonary edema, and death. no effective drug has been approved for clinical use. this study investigated the antiviral effects of flavonoids against ev-a71. an in vitro inhibitor screening assay using recombinant ev-a71 3c protease (3cpro) demonstrated fisetin and rutin inhibiting 3cpro enzymatic activity in a dose-dependent manner. cell-based fluorescence resonance energy transfer (fret) assay with an ev-a71 3cpro cleavage mot ...201222465253
expression and immunogenicity of novel subunit enterovirus 71 vp1 antigens.hand, foot, and mouth disease (hfmd) is a common viral illness in young children. hfmd is caused by viruses belonging to the enterovirus genus of the picornavirus family. recently, enterovirus 71 (ev71) has emerged as a virulent agent for hfmd with severe clinical outcomes. in the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit vp1 antigen for the design of ev71 vaccines. dna immunization was adopted as a simple technical ap ...201222450314
viral and host factors that contribute to pathogenicity of enterovirus 71.the single-stranded rna virus enterovirus 71 (ev71), which belongs to the picornaviridae family, has caused epidemics worldwide, particularly in the asia-pacific region. most ev71 infections result in mild clinical symptoms, including herpangina and hand, foot and mouth disease. however, serious pathological complications have also been reported, especially for young children. the mechanisms of ev71 disease progression remain unclear. the pathogenesis of adverse clinical outcomes may relate to m ...201222439724
[epidemiologic characteristics of hand-foot-mouth disease in guiyang between 2008 and 2010].to study the epidemiologic characteristics of hand-foot-mouth disease (hfmd) in guiyang between 2008 and 2010.201222433407
increased frequency of th17 cells in the peripheral blood of children infected with enterovirus 71.enterovirus 71 (ev71) affects the health of young children globally causing severe neurologic diseases. the relationship between ev71 infection and t helper type 17 (th17) has not been described, although this new th subset or interleukin-17 (il-17) has been reported to be associated with other viral infections. the purpose of the current study was to describe the immune profile involving th17 cells, neutrophils, and related factors and to speculate on the possible immunopathogenesis of ev71 inf ...201222431024
safety and immunogenicity of a novel human enterovirus 71 (ev71) vaccine: a randomized, placebo-controlled, double-blind, phase i clinical trial.there is an urgent need for a novel vaccine that is effective against human enterovirus 71 (ev71) outbreaks. a double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human ev71 vaccine in healthy adults, children and infants. the vaccine dosages were 200 u and 400 u for children and adults, and 100 u, 200 u and 400 u for infants. subjects were randomized to receive different dosages of the vaccine or placebo. adults received intramuscular injection on days 0 ...201222426327
bilirubin: an endogenous molecule with antiviral activity in vitro.bilirubin-ix-alpha (br) is the final product of heme metabolism through the heme oxygenase/biliverdin reductase (ho/bvr) system. previous papers reported on the microbicidal effects of the ho by-products biliverdin-ix-alpha, carbon monoxide and iron, through either direct or indirect mechanisms. in this paper the evidence of a virucidal effect of br against human herpes simplex virus type 1 (hsv-1) and the enterovirus ev71 was provided. bilirubin-ix-alpha, at concentrations 1-10 μm, close to tho ...201222408623
a reverse genetic study of the adaptation of human enterovirus 71 to growth in chinese hamster ovary cell cultures.we selected chinese hamster ovary (cho) cell-adapted strains of human enterovirus 71 (hev71) belonging to sub-genogroups b5 (hev71-b5) and c2 (hev71-c2) by serial passage in cho cells at a high multiplicity of infection. during the course of cho cell passage, virus growth improved significantly, with increasing virus titres and the presence of cytopathic effect observed. a study of virus growth kinetics revealed that the cho cell-adapted strains of hev71-b5 (cho-b5) and hev71-c2 (cho-c2) grew ef ...201222406130
a sensor-adaptor mechanism for enterovirus uncoating from structures of ev71.enterovirus 71 (ev71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. no vaccine or antiviral therapy is available. high-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. in contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in ato ...201222388738
crystal structure of human enterovirus 71.enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. here, we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the "pocket factor," a small molecule that stabilizes the virus, is partly exposed on the floor of the "canyon." thus, the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.201222383808
scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases.enterovirus 71 (ev71) is one of the major causative agents of hand, foot, and mouth disease (hfmd). infection with ev71 is occasionally associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. because cellular receptors for viruses play an important role in cell, tissue, and species tropism, it is important to identify and characterize the receptor molecule. recently, cellular receptors and host factors that stimulate ev71 inf ...201222363322
characterization and specificity of the linear epitope of the enterovirus 71 vp2 protein.enterovirus 71 (ev71) has emerged as a major causative agent of hand, foot and mouth disease in the asia-pacific region over the last decade. hand, foot and mouth disease can be caused by different etiological agents from the enterovirus family, mainly ev71 and coxsackieviruses, which are genetically closely related. nevertheless, infection with ev71 may occasionally lead to high fever, neurologic complications and the emergence of a rapidly fatal syndrome of pulmonary edema associated with brai ...201222361222
identification of a c2 subgenogroup strain of enterovirus 71 in a retrospective study in shandong province, china, from 1990 to 2010. 201222357503
development of a transcription-reverse transcription concerted reaction method for specific detection of human enterovirus 71 from clinical specimens.a transcription-reverse transcription (rt) concerted reaction (trcr) method was developed for rapid and specific detection of ev71 from clinical specimens. this method was validated with ev71 strains from all of the known genotypes (genotypes a, b1 to b5, and c1 to c5), with detection limits of 10 to 10(3) copies, and was useful for identification of ev71 from throat swabs of patients with hand, foot, and mouth disease (hfmd).201222357494
incidence rates of enterovirus 71 infections in young children during a nationwide epidemic in taiwan, 2008-09.enterovirus 71 (ev71) is causing life-threatening outbreaks in tropical asia. in taiwan and other tropical asian countries, although nationwide ev71 epidemics occur cyclically, age-specific incidence rates of ev71 infections that are critical to estimate disease burden and design vaccine trials are not clear. a nationwide ev71 epidemic occurred in 2008-09 in taiwan, which provided a unique opportunity to estimate age-specific incidence rates of ev71 infections.201222348156
[experimental studies on infant tupaia belangeri chineses with ev71 infection].tupaia belangeri are small mammals with a squirrel-like appearance; they were formerly classified under the primates order despite the lack of derived features characteristic of primates. given that t. belangeri are easy to raise, cheap to maintain, and have a small body size, a high reproductive rate, and close affinity to primates, these animals would be used as an alternative to primates in biomedical research. three-month old t. belangeri chineses were infected with enterovirus 71 (ev71) via ...201222345002
antiviral effect of geraniin on human enterovirus 71 in vitro and in vivo.human enterovirus 71 infection causes hand, foot and mouth disease in children under 6 years of age and has caused mortalities in large-scale outbreaks in the asia-pacific region. no effective vaccine or antiviral drugs currently exist against enterovirus 71 in the clinic. in this study, we investigated the antiviral effect of geraniin on enterovirus 71 both in vitro and in vivo. the results showed that geraniin effectively inhibited virus replication in rhabdomyosarcoma cells with an ic(50) of ...201222342145
screening and detection of human enterovirus 71 infection by a real-time rt-pcr assay in marseille, france, 2009-2011.enterovirus-positive samples diagnosed in marseille (january 2009 to september 2011) were screened for ev71 by real-time rt-pcr. ev71 was detected in three children below the age of 2 years with no history of overseas travel; two of these cases were associated with severe clinical presentation. viruses demonstrated genetic similarity to other european genogroup c2 strains. strain mrs/09/3663 complete sequencing revealed 97.6% identity across the entire genome with a 2008 singapore isolate, witho ...201222332991
major vault protein: a virus-induced host factor against viral replication through the induction of type-i interferon.major vault protein (mvp) is the major constituent of vaults and is involved in multidrug resistance, nucleocytoplasmic transport, and cell signaling. however, little is known about the role of mvp during viral infections. in this study, high levels of mvp were found in peripheral blood mononuclear cells, sera, and liver tissue from patients infected with hepatitis c virus (hcv) relative to healthy individuals. hcv infections resulted in elevated levels of mvp messenger rna (mrna) and protein ex ...201222318991
genetic analysis of the p1 region of human enterovirus 71 strains and expression of the 55 f strainvp1 protein.enterovirus 71 (ev71) is a member of the entero-virus genus of the picornaviridae family and is the major cause of hand, foot, and mouth disease (hfmd) in children. different strains from gansu were cloned and the p1 protein was sequenced and analysed. results indicate that there are three kinds of ev71 infections prevalent in gansu. the vp1 protein from one of these strains, 55f, was expressed. the recombinant protein was expressed with high level and reacted specifically with the ev71 patient ...201222270802
seroepidemiology of enterovirus 71 infection prior to the 2011 season in children in shanghai.in 2010, china experienced the largest outbreak on record of enterovirus 71 (ev71)-associated hand foot and mouth disease (hfmd) with more than 1.7 million cases, 27,000 patients with severe neurological complications and 905 deaths. understanding of the seroprevalence of neutralizing antibodies (nab) against ev71 and their protective role against hfmd in children is crucial for the implementation of future therapeutic and prophylactic intervention.201222265829
enterovirus 71 viral capsid protein linear epitopes: identification and characterization.to characterize the human humoral immune response against enterovirus 71 (ev71) infection and map human epitopes on the viral capsid proteins.201222264266
association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease.enterovirus 71 (ev71) is one of the common causative agents of hand, foot and mouth disease (hfmd), and is associated with several outbreaks with neurological complications including encephalitis. this study investigated the polymorphisms of interferon gamma (ifn-γ)+874 t/a and interleukin 10 (il-10)-1082 g/a in 65 chinese patients with ev71 encephalitis and 113 chinese hfmd patients without complications. the polymorphisms of ifn-γ+874 t/a and il-10-1082 g/a were determined by polymerase chain ...201222263663
mri findings of neurological complications in hand-foot-mouth disease by enterovirus 71 infection.to explore the imaging characterization of neurological complications associated with the enterovirus 71 (ev71) epidemics.201222248036
enterovirus 71 encephalomyelitis and japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and rna.to investigate if two important epidemic viral encephalitis in children, enterovirus 71 (ev71) encephalomyelitis and japanese encephalitis (je) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished.201222236252
molecular determinants of enterovirus 71 viral entry: cleft around gln-172 on vp1 protein interacts with variable region on scavenge receptor b 2.enterovirus 71 (ev71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the asia-pacific region in recent years. human scavenger receptor class b 2 (scarb2) is the main cellular receptor for ev71 on target cells. the requirements of the ev71-scarb2 interaction have not been fully characterized, and it has not been determined whether scarb2 serves as an uncoating receptor for ev71. here we compared the efficiency of the receptor from different s ...201222219187
a colorimetric-based accurate method for the determination of enterovirus 71 titer.the 50 % tissue culture infectious dose (tcid50) is still one of the most commonly used techniques for estimating virus titers. however, the traditional tcid50 assay is time consuming, susceptible to subjective errors and generates only quantal data. here, we describe a colorimetric-based approach for the titration of enterovirus 71 (ev71) using a modified method for making virus dilutions. in summary, the titration of ev71 using mtt or mts staining with a modified virus dilution method decrease ...201224293817
immunization of n terminus of enterovirus 71 vp4 elicits cross-protective antibody responses.enterovirus 71 (ev71) is major cause of hand, foot and mouth disease. large epidemics of ev71 infection have been recently reported in the asian-pacific region. currently, no vaccine is available to prevent ev71 infection.201324320792
[development of ev71, ca16 and other enterovirus vrial real-time qualitative pcr diagnostic kit].a novel multiplex real-time rt-pcr kit was developed to detect ev71, coxa16 and other human enteroviruses simultaneously with an internal amplification control to avoids false negatives, which used for hand, foot and mouth disease in the clinical diagnosis and epidemiological surveillance.201324319965
[sero-epidemiological analysis for entervirus 71 infection of adults in beijing].to evaluate the enterovirus 71 (ev 71) protective antibody level of health adults people in beijing.201324319947
the cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.ev71 is one of major etiologic causes of hand-foot-mouth disease (hfmd) and leads to severe neurological complications in young children and infants. recently inactivated ev71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. however, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because rna recombination is seen more frequently in ev71 epidemics.201324260259
antiviral activity of guiqi polysaccharides against enterovirus 71 in vitro.in this study, we have investigated the antiviral activity of guiqi polysaccharides (gqp) upon enterovirus 71 (ev71) in vitro. an assay using methyl thiazolyl tetrazolium (mtt), and analyses of cytopathic effects (cpe) were used to examine the antiviral activity of gqp upon vero cells infected with ev71. the results revealed that gqp at concentrations below 31.2 μg/ml exhibited significant antiviral effects upon ev71 when applied under three different experimental protocols. gqp was most strongl ...201324254889
preclinical evaluation of the immunogenicity and safety of an inactivated enterovirus 71 candidate vaccine.human enterovirus 71 (ev71) is a significant cause of morbidity and mortality from hand, foot and mouth disease (hfmd) and neurological complications, particularly in young children in the asia-pacific region. there are no vaccines or antiviral therapies currently available for prevention or treatment of hfmd caused by ev71. therefore, the development of therapeutic and preventive strategies against hfmd is of growing importance. we report the immunogenic and safety profile of inactivated, purif ...201324244774
structure of limp-2 provides functional insights with implications for sr-bi and cd36.members of the cd36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. they recognize normal and modified lipoproteins, as well as pathogen-associated molecular patterns. the family consists of three members: sr-bi (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis c virus), limp-2/lgp85 (which mediates lysosomal delivery of β-glucocerebrosidase and serves as a receptor for enterovirus 71 ...201324162852
a one-step dipstick assay for the on-site detection of nucleic acid.we have developed a one-step nucleic acid dipstick assay (nada) for visually detecting polymerase chain reaction (pcr) products within 3min. "one-step" means that there were no additional procedures between amplification and detection.201324161476
bedside immunochromatographic test for enterovirus 71 infection in children.enterovirus 71 (ev71) causes frequent outbreaks worldwide, particularly in the asia-pacific area. its quick spread is a critical challenge for public health and timely preventive measures and clinical management therefore rely on early detection. there is a need for a rapid, easy-to-use, and reliable method for detecting ev71 infections.201324084600
is a monovalent vaccine against enterovirus 71 sufficient? a review of enterovirus 71 vaccine development based on enterovirus surveillance in taiwan. 201324079713
enterovirus 71 vp1 activates calmodulin-dependent protein kinase ii and results in the rearrangement of vimentin in human astrocyte cells.enterovirus 71 (ev71) is one of the main causative agents of foot, hand and mouth disease. its infection usually causes severe central nervous system diseases and complications in infected infants and young children. in the present study, we demonstrated that ev71 infection caused the rearrangement of vimentin in human astrocytoma cells. the rearranged vimentin, together with various ev71 components, formed aggresomes-like structures in the perinuclear region. electron microscopy and viral rna l ...201324073199
environmental alkylphenols modulate cytokine expression in plasmacytoid dendritic cells.alkylphenols, such as nonylphenol (np) and 4-octylphenol (4-op), have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. plasmacytoid dendritic cells (pdcs) can secrete large amounts of type i ifns and are critical in immune regulation. however, there has been limited study about the influence of alkylphenols on the function of pdcs.201324039973
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