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challenges to licensure of enterovirus 71 vaccines.human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (ev71), which frequently involve neurological complications. ev71 vaccines are being evaluated in humans. however, several challenges to licensure of ev71 vaccines need to be addressed. firstly, ev71 and coxsackievirus a (ca) are frequently found to co-circulate and cause hand-foot-mouth disease (hfmd). a polyvalent vaccine that can provide protection against ev71 and prevalent ca are desirable. seco ...201222953003
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
coxsackievirus mutants that can bypass host factor pi4kiiiβ and the need for high levels of pi4p lipids for replication.rna viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are unlikely to mutate in response to therapy. we recently demonstrated that phosphatidylinositol-4-kinase iiiβ (pi4kiiiβ) and its product phosphatidylinositol-4-phosphate (pi4p) are essential for replica ...201222945356
[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
identification and characterization of a monoclonal antibody recognizing the linear epitope rvadvi on vp1 protein of enterovirus 71.several large outbreaks of hand-foot-mouth disease (hfmd) have occurred in the asian-pacific region since 1997, with enterovirus 71 (ev71) and/or coxsackievirus a16 (cav16) as the main causative agents. despite the close genetic relationship between the two viruses, only ev71 is associated with severe clinical manifestations and deaths. effective antiviral treatment and vaccines are not available. high-quality monoclonal antibodies (mabs) are necessary to improve the accuracy of the diagnosis of ...201222930511
far upstream element binding protein 1: a commander of transcription, translation and beyond.the far upstream binding protein 1 (fbp1) was first identified as a dna-binding protein that regulates c-myc gene transcription through binding to the far upstream element (fuse) in the promoter region 1.5 kb upstream of the transcription start site. fbp1 collaborates with tfiih and additional transcription factors for optimal transcription of the c-myc gene. in recent years, mounting evidence suggests that fbp1 acts as an rna-binding protein and regulates mrna translation or stability of genes, ...201222926519
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
evidences for intertypic and intratypic recombinant events in ev71 of hand, foot and mouth disease during an epidemic in hubei province, china, 2011.humane enterovirus 71 (hev 71) is a common contagious agent of hand, foot and mouth disease (hfmd) which is normally mild but can caused deaths and severe neurological complications. in april 2011, an unpredicted hfmd outbreak in xiangyang city of hubei province in china resulted in a high aggregation of hfmd cases including fatal cases and many severe cases. in this study, 71 clinical specimens were collected according to the different symptoms and rna extraction and rt-pcr amplification were p ...201222922556
a novel minicircle vector based system for inhibting the replication and gene expression of enterovirus 71 and coxsackievirus a16.enterovirus 71 (ev 71) and coxsackievirus a16 (ca 16) are two major causative agents of hand, foot and mouth disease (hfmd). they have been associated with severe neurological and cardiological complications worldwide, and have caused significant mortalities during large-scale outbreaks in china. currently, there are no effective treatments against ev 71 and ca 16 infections. we now describe the development of a novel minicircle vector based rna interference (rnai) system as a therapeutic approa ...201222921338
encephalomyocarditis virus viroporin 2b activates nlrp3 inflammasome.nod-like receptors (nlrs) comprise a large family of intracellular pattern- recognition receptors. members of the nlr family assemble into large multiprotein complexes, termed the inflammasomes. the nlr family, pyrin domain-containing 3 (nlrp3) is triggered by a diverse set of molecules and signals, and forms the nlrp3 inflammasome. recent studies have indicated that both dna and rna viruses stimulate the nlrp3 inflammasome, leading to the secretion of interleukin 1 beta (il-1β) and il-18 follow ...201222916014
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
replication kinetics of coxsackievirus a16 in human rhabdomyosarcoma cells.coxsackievirus a16 (cva16), together with enterovirus type 71 (ev71), is responsible for most cases of hand, foot and mouth disease (hfmd) worldwide. recent findings suggest that the recombination between cva16 and ev71, and the co-circulation of these two viruses may have contributed to the increase of hfmd cases in china over the past few years. it is therefore important to further understand the virology, epidemiology, virus-host interactions and host pathogenesis of cva16. in this study, we ...201222899429
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
[etiology of hand-foot-and-mouth disease seen in nanjing in 2010 and molecular characteristics analysis of ev71].to study the etiological agent of hand-foot-and-mouth disease (hfmd), and to genetically characterize enterovirus 71 (ev71) isolated from clinical specimens of hfmd patients in nanjing in 2010.201222801226
[epidemiology and etiology of hand-foot-and-mouth disease seen in jiangsu province from 2008 to 2010].to analyze the etiological and epidemiological characteristics of hand-foot-and-mouth disease (hfmd) seen in jiangsu province from 2008 to 2010, and provide evidence for its prevention and control.201222801225
[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
antiviral ability of kalanchoe gracilis leaf extract against enterovirus 71 and coxsackievirus a16.pandemic infection or reemergence of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. however, effective therapeutic drugs against ev71 and cva16 are rare. kalanchoe gracilis (l.) dc is used for the treatment of injuries, pain, and inflammation. this study investigated antiviral effects of k. gracilis leaf extr ...201222666293
copi is required for enterovirus 71 replication.enterovirus 71 (ev71), a member of the picornaviridae family, is found in asian countries where it causes a wide range of human diseases. no effective therapy is available for the treatment of these infections. picornaviruses undergo rna replication in association with membranes of infected cells. copi and copii have been shown to be involved in the formation of picornavirus-induced vesicles. replication of several picornaviruses, including poliovirus and echovirus 11 (ev11), is dependent on cop ...201222662263
antigenic characteristics of the complete and truncated capsid protein vp1 of enterovirus 71.the complete vp1 protein of enterovirus 71 (ev71) and a series of truncations were expressed in escherichia coli and their antigenic characteristics were studied. immunoblot analysis showed the major immunoreactive region of the vp1 protein was located in the n-terminal portion at position of amino acid (aa) 1-100. the complete vp1 possessed strong cross-reactivity with antisera against coxsackievirus a16 (ca16) and echovirus 6 (echo6), while the truncated fragment at position 1-100 aa only had ...201222659489
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
[outbreak of acute enterovirus intestinal infection in sakhalin region in august 2010].the investigation of cases of acute intestinal infections in the sakhalin region of russia in august, 2010 is described. epidemiological and molecular biological studies were conducted. after initial pcr screening and determining the nucleotide sequences of the positive samples the following enteroviruses were found: coxsackie a2 - 42 samples (45%), coxsackie a4--31 sample (34%), enterovirus 71--6 samples (6,5%), coxsackievirus b5--6 samples (6,5%), coxsackie b3--4 samples (4%) and coxsackie b1- ...201222642180
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
inhibition of enterovirus 71 (ev-71) infections by a novel antiviral peptide derived from ev-71 capsid protein vp1.enterovirus 71 (ev-71) is the main causative agent of hand, foot and mouth disease (hfmd). in recent years, ev-71 infections were reported to cause high fatalities and severe neurological complications in asia. currently, no effective antiviral or vaccine is available to treat or prevent ev-71 infection. in this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of ev-71. ninety five synthetic peptides (15-mers) overlapping the entire e ...201222563456
pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia and now is being recognized as an important neurotropic virus. effective medications and prophylactic vaccine against ev71 infection are urgently needed. based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated ev71 vaccine candidate has been developed and currently in human phase 1 clinical trial.201222529942
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
simultaneous detection of enterovirus 71 and coxsackievirus a16 using dual-colour upconversion luminescent nanoparticles as labels.we highlight a novel fluorescence analysis for sensitive and selective detection of ev-71 and cv-a16 by combining labelling technology based on dual-colour upconversion fluorescence nanoparticles (ucnps) with magnetic bioseparation and concentration technology based on magnetite nanoparticles (mnps).201222498910
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
cellular receptors for human enterovirus species a.human enterovirus species a (hev-a) is one of the four species of hev in the genus enterovirus in the family picornaviridae. among hev-a, coxsackievirus a16 (cva16) and enterovirus 71 (ev71) are the major causative agents of hand, foot, and mouth disease (hfmd). some other types of hev-a are commonly associated with herpangina. although hfmd and herpangina due to hev-a are common febrile diseases among infants and children, ev71 can cause various neurological diseases, such as aseptic meningitis ...201222470371
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
occurrence of hand-foot-and-mouth disease pathogens in domestic sewage and secondary effluent in xi'an, china.hand, foot and mouth disease (hfmd), caused by a group of enteric viruses such as enterovirus 71 (ev71), coxsackievirus a16 (cva16) and coxsackievirus a10 (cva10), is heavily epidemic in east asia. this research focused on investigating the occurrence of hfmd pathogens in domestic sewage and secondary effluent before disinfection in a wastewater treatment plant (wwtp) in xi'an, the largest megacity in northwest china. in order to simultaneously detect all three hfmd pathogens, a semi-nested rt-p ...201222446307
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
human scarb2-dependent infection by coxsackievirus a7, a14, and a16 and enterovirus 71.human enterovirus species a (hev-a) consists of at least 16 members of different serotypes that are known to be the causative agents of hand, foot, and mouth disease (hfmd), herpangina, and other diseases, such as respiratory disease and polio-like flaccid paralysis. enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hfmd. cva5, cva6, cva10, and cva12 mainly cause herpangina or are occasionally involved with sporadic cases of hfmd. we have previously shown tha ...201222438546
[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
outbreak of hand, foot and mouth disease/herpangina associated with coxsackievirus a6 and a10 infections in 2010, france: a large citywide, prospective observational study.hand, foot and mouth disease (hfmd) and herpangina (ha) are frequently caused by several distinct serotypes belonging to the human enterovirus a species (heva). enterovirus 71 is considered as a significant public health threat because of rare but fatal neurological complications. a sentinel surveillance system involving paediatricians from clermont-ferrand (france) was set up to determine the clinical and epidemiological characteristics of hfmd/ha associated with enterovirus infections. a stand ...201222404077
[studies on anti-ev71 virus activity of traditional chinese medicine and its clinical application in treatment of hfmd].hand-foot-and-mouth disease is caused by intestinal virus infection. the viruses coxsackie a16 (ca16) and enterovirus 71 (ev71) are the main pathogens. between them, the virus ev71 is more dangerous and easier to cause serious complications, which leads to death or disability. currently, there are no effective antiviral drugs to treat ev71 infection. therefore, developing an effective drug against ev71 virus activity is significant. it has a huge potency of screening the anti-ev71 components and ...201122393752
simultaneous determination of human enterovirus 71 and coxsackievirus b3 by dual-color quantum dots and homogeneous immunoassay.human enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have high risks for morbidity and mortality. a virus quantitation immunoassay has been proposed by employing two colored quantum dots (qds), antibodies of the virus, and graphene oxide (go). the qds are streptavidin-conjugated quantum dots (sa-qds), and the antibodies are biotinylated antibodies. biotinylated ev71 antibody (ab1) was associated with 525 nm green colored sa-qds via biotin-streptavidin interaction forming qds-ab1, whereas bio ...201222390751
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
a flavobacterium lindanitolerans strain isolated from the ascites sample of a chinese patient with ev71 virus infection.a strain of flavobacterium lindanitolerans isolated from a sick child's ascites was described. the 16s rrna gene of the strain was 100% identical to that of flavobacterium lindanitolerans which was first identified in india in 2008. it was first described that the isolate required x factor (hemin) for growth in the optimal conditions of 37 °c with 5% co(2). the isolate produced indole and h(2)s. it did not present hemolytic feature on blood agar.201122365408
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
[virologic and epidemiological characteristics of non-polio infection in croatia over a ten-year period (2000-2009)].the aim of the present study was to show the virologic and epidemiological characteristics of non-polio enterovirus (npev) infection over a ten-year period in croatia.201122359891
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
[a pathogen analysis within 174 cases of hand-foot-mouth disease in the summer of 2009].to analyze the pathogen and characteristics of the serum types of enterovirus of hand-foot-and-mouth disease (hfmd) in the summer, 2009.201122338230
molecular characterization of human enteroviruses in the central african republic: uncovering wide diversity and identification of a new human enterovirus a71 genogroup.human enteroviruses (hev) are among the most common viruses infecting humans. their circulation has been widely studied in most parts of the world but not in sub-saharan africa, where poliomyelitis remains prevalent. we report here the molecular characterization of 98 nonpoliovirus (non-pv) hev strains isolated from 93 randomly selected cell culture-positive supernatants from stool samples collected from 1997 through 2006 from children with acute flaccid paralysis living in the central african r ...201222337981
[analysis on detection of enterovirus nucleotides in feces samples of hand-foot-mouth disease patients after recovery].to explore the duration of enterovirus (ev) nucleotides positive in feces samples of hand-foot-mouth disease (hfmd) patients after recovery.201122336339
[acute kidney injury in critically ill children infected with influenza a virus (h1n1) and enterovirus 71].to analyze the clinical characteristics of acute kidney injury (aki) in critically ill childhood patients with influenza a virus (h1n1) and enterovirus 71 (ev71), and to study the significance of the serum creatinine and urine output in diagnosis of aki.201122336307
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
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