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[thinking about the intervention strategy for critically ill hand-foot-and-mouth disease caused by enterovirus 71 infection]. 201222801222
[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
[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
[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
[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
[progress in research on acute pulmonary edema caused by enterovirus 71]. 201222801228
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
etiologic and epidemiologic analysis of hand, foot, and mouth disease in guangzhou city: a review of 4,753 cases.this study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (hfmd) cases that occurred between 2008 and 2010 in guangzhou city, to help develop and implement precautionary measures applicable for future outbreaks.201222964289
[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
[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
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
infectious disease experts monitor outbreaks of enterovirus 71 in asia. 201222988146
production of ev71 vaccine candidates.enterovirus 71 (ev71) is now recognized as an emerging neurotropic virus in asia and with coxsackie virus (cv) it is the other major causative agent of hand-foot-mouth diseases (hfmd). effective medications and/or prophylactic vaccines against hfmd are urgently needed. from a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of d ...201222992566
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
enterovirus 71 blocks selectively type i interferon production through the 3c viral protein in mice.type i interferons (ifns) represent an essential innate defense mechanism for controlling enterovirus 71 (ev 71) infection. mice inoculated with ev 71 produced a significantly lower amount of type i ifns than those inoculated with poly (i:c), adenovirus type v, or coxsackievirus b3 (cb3). ev 71 infection, however, mounted a proinflammatory response with a significant increase in the levels of serum and brain interleukin (il)-6, monocyte chemoattractant protein-1, tumor necrosis factor, and ifn-γ ...201222997081
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
[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
immunological evaluation and comparison of different ev71 vaccine candidates.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are major causative agents of hand, foot, and mouth diseases (hfmds), and ev71 is now recognized as an emerging neurotropic virus in asia. effective medications and/or prophylactic vaccines against hfmd are not available. the current results from mouse immunogenicity studies using in-house standardized rd cell virus neutralization assays indicate that (1) vp1 peptide (residues 211-225) formulated with freund's adjuvant (cfa/ifa) elicited low v ...201223008736
comparative genetic analysis of vp4, vp1 and 3d gene regions of enterovirus 71 and coxsackievirus a16 circulating in malaysia between 1997-2008.three genomic regions, vp4 capsid, vp1 capsid and 3d rna polymerase of human enterovirus 71 (ev-71) and coxsackievirus a16 (cv-a16) were sequenced to understand the evolution of these viruses in malaysia. a total of 42 ev-71 and 36 cv-a16 isolates from 1997- 2008 were sequenced. despite the presence of many ev-71 subgenotypes worldwide, only subgenotypes b3, b4, b5, c1 and c2 were present in malaysia. importation of other subgenotypes such as c3, c4/d and c5 from other countries was infrequent. ...201223018509
cross-reactive neutralizing antibody epitopes against enterovirus 71 identified by an in silico approach.currently, infections of hand, foot and mouth disease (hfmd) due to human enterovirus 71 (ev71) cannot be prevented or treated, as there are no suitable vaccines or antiviral drugs. this study aimed to identify potential vaccine candidates for ev71 using in silico analysis of its viral capsid proteins. a combined in silico approach utilizing computational hidden markov model (hmm), propensity scale algorithm, and artificial learning, identified three 15-mer structurally conserved b-cell epitope ...201223022400
comparative analysis of the immunogenicity and protective effects of inactivated ev71 vaccines in mice.enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd). three inactivated ev71 whole-virus vaccines of different strains developed by different manufacturers in mainland china have recently entered clinical trials. although several studies on these vaccines have been published, a study directly comparing the immunogenicity and protective effects among them has not been carried out, which makes evaluating their relative effectiveness difficult. thus, properly c ...201223029378
characterization of enterovirus 71 capsids using subunit protein-specific polyclonal antibodies.enterovirus 71 (ev71), a member of the enterovirus genus of the picornaviridae family, is one of the major causative agents of hand-foot-and-mouth disease (hfmd), which is prevalent in the asia-pacific region. in this article, a set of capsid subunit protein-specific antibodies was used to characterize the ev71 structural protein processing and to determine the composition and assembly of ev71 capsids. sds-page and western blot analyses showed that the capsids of a purified ev71 preparation, whi ...201323046991
enterovirus 71 vpg uridylation uses a two-molecular mechanism of 3d polymerase.vpg uridylylation is essential for picornavirus rna replication. the vpg uridylylation reaction consists of the binding of vpg to 3d polymerase (3d(pol)) and the transfer of ump by 3d(pol) to the hydroxyl group of the third amino acid tyr of vpg. previous studies suggested that different picornaviruses employ distinct mechanisms during vpg binding and uridylylation. here, we report a novel site (site-311, located at the base of the palm domain of ev71 3d(pol)) that is essential for ev71 vpg urid ...201223055549
adoptive transfer of macrophages from adult mice reduces mortality in mice infected with human enterovirus 71.human enterovirus 71 (ev71) causes hand, foot and mouth disease in children under 6 years of age, and the neurological complications of this virus can lead to death. until now, no vaccines or drugs have been available for the clinical control of this epidemic. macrophages can engulf pathogens and mediate a series of host immune responses that play a role in the defence against infectious diseases. using immunohistochemistry, we observed the localizations of virus in muscle tissues of ev71-infect ...201323065110
the association between enterovirus 71 infections and meteorological parameters in taiwan.enterovirus 71 (ev71) infections are a significant cause of neurological disorder and death in children worldwide. seasonal variations in ev71 infections have been recognized, but the mechanisms responsible for this phenomenon remain unknown. the purpose of this study was to examine the relationship between meteorological parameters and ev71 infection.201223071650
rna polymerase i-driven reverse genetics system for enterovirus 71 and its implications for vaccine production.enterovirus 71 (ev71) is a virus that causes from mild hand, foot and mouth disease (hfmd) to severe neurological complications and deaths in infants and young children. effective antiviral agents and vaccines against ev71 are not available. however, vero cell-based chemically inactivated ev71 vaccines could be developed soon based on the success of inactivated polio vaccine. like poliovirus, ev71 has a positive single-stranded rna genome of about 7400 nucleotides which contains a single open re ...201223072515
detection of human enterovirus 71 and coxsackievirus a16 in an outbreak of hand, foot, and mouth disease in henan province, china in 2009.during 2009, an outbreak of hand, foot, and mouth disease (hfmd) enrolled 490 people in henan province, causing the death of two children. in order to investigate the pathogens responsible for this outbreak and characterize their genetic characteristics, a total of 508 clinical specimens (stool, throat swab, and vesicle fluid) were collected from the center for disease control and prevention of henan province. virological investigations (virus isolation, conventional reverse transcription pcr, a ...201323080402
antigenic analysis of divergent genotypes human enterovirus 71 viruses by a panel of neutralizing monoclonal antibodies: current genotyping of ev71 does not reflect their antigenicity.in recent year, enterovirus 71 (ev71)-associated hand, foot and mouth disease (hfmd) has become an important public health issue in china. ev71 has been classified into genotypes a, b1-b5 and c1-c5. with such genetic diversity, whether the convalescent or recovery antibody responses can cross-protect infections from other genotypes remains a question. understanding of the antigenicity of such diverse genetic ev71 isolates is crucial for the ev71 vaccine development. here, a total of 186 clones a ...201323088887
antigenic diversity of enteroviruses associated with nonpolio acute flaccid paralysis, india, 2007-2009.because of the broadened acute flacid paralysis (afp) definition and enhanced surveillance, many nonpolio afp (np-afp) cases have been reported in india since 2005. to determine the spectrum of nonpolio enterovirus (npev) serotypes associated with np-afp from polio-endemic and -free regions, we studied antigenic diversity of afp-associated npevs. of fecal specimens from 2,786 children with np-afp in 1 polio-endemic and 2 polio-free states, 823 (29.5%) were positive for npevs in rd cells, of whic ...201223092622
enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor.enterovirus 71 (ev-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. to date, four ev-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish ev-71 infection, implying that there is an as yet undiscovered receptor(s). since ev-71 has a wide range of tissue tropisms, we hypothesize that ev-71 infections ma ...201223097443
quantification of the dynamics of enterovirus 71 infection by experimental-mathematical investigation.enterovirus 71 (ev71) is the causative agent of hand-foot-and-mouth disease and can trigger neurological disorders. ev71 outbreaks are a major public health concern in asia-pacific countries. by performing experimental-mathematical investigation, we demonstrate here that viral productivity and transmissibility but not viral cytotoxicity are drastically different among ev71 strains and can be associated with their epidemiological backgrounds. this is the first report demonstrating the dynamics of ...201323097444
seroepidemiology of human enterovirus71 and coxsackievirusa16 in jiangsu province, china.the major etiology of hand, foot and mouth disease (hfmd) is infection with human enterovirus a (hev-a). among subtypes of hev-a, coxsackievirusa16 (coxa16) and enterovirus 71 (ev71) are major causes for recurrent hfmd among infants and children in jiangsu province, mainland china. here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human ev71 and coxa16 infections in infants and children aged 0 to 15 years. the results may ...201223102275
fluorescent primer-based in vitro transcription system of viral rna-dependent rna polymerases.viral infection is a leading cause of disease and death. although vaccines are the most effective method of controlling viral infections, antiviral drugs are also important. here, we established an in vitro transcription system by using fluorescein isothiocyanate-conjugated primers for rna polymerases of viruses that are important disease-causing human pathogens (influenza, hepatitis c, japanese encephalitis viruses, and enterovirus 71). this technology will allow us to analyze rna polymerase ac ...201323103398
enterovirus infection in korean children and anti-enteroviral potential candidate agents.although most enterovirus infections are not serious enough to be life threatening, several enteroviruses such as enterovirus 71 are responsible for severe, potentially life-threatening disease. the epidemic patterns of enteroviruses occur regularly during the year, but they may change due to environmental shifts induced by climate change due to global warming. therefore, enterovirus epidemiological studies should be performed continuously as a basis for anti-viral studies. a great number of syn ...201223133481
cd4 t-cell-independent antibody response reduces enterovirus 71 lethality in mice by decreasing tissue viral loads.enterovirus 71 (ev71) has induced fatal encephalitis in hundreds of thousands of infants and young children in the asia-pacific region since the past decade. lymphocyte and antibody responses have been suspected to aggravate ev71-induced neurological symptoms, so anti-inflammatory agents have been used to treat patients with neurological symptoms. in the present study, we found that mice deficient in cd4(+) t cells were resistant to ev71 infection as wild-type mice, whereas mice deficient in b c ...201223133489
comparing molecular methods for early detection and serotyping of enteroviruses in throat swabs of pediatric patients.enteroviruses include over 100 serotypes and usually cause self-limited infections with non-specific symptoms in children, with the exceptions of polioviruses and enterovirus 71 which frequently cause neurologic complications. therefore, early detection and serotyping of enteroviruses are critical in clinical management and disease surveillance. traditional methods for detection and serotyping of enteroviruses are virus isolation and immunofluorescence assay, which are time-consuming. in this st ...201223133580
antiviral activity of punicalagin toward human enterovirus 71 in vitro and in vivo.human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children and has caused mortalities in large-scale outbreaks in the asia-pacific region in recent years. no vaccine or antiviral therapy is available currently in the clinic. in this work, we investigated the antiviral effect of punicalagin on enterovirus 71 both in vitro and in vivo. the results showed that punicalagin reduced the viral cytopathic effect on rhabdomyosarcoma cells with an ic₅₀) value of ...201223146421
microrna-548 down-regulates host antiviral response via direct targeting of ifn-λ1.interferon (ifn)-mediated pathways are a crucial part of the cellular response against viral infection. type iii ifns, which include ifn-λ1, 2 and 3, mediate antiviral responses similar to type i ifns via a distinct receptor complex. ifn-λ1 is more effective than the other two members. transcription of ifn-λ1 requires activation of irf3/7 and nuclear factor-kappa b (nf-κb), similar to the transcriptional mechanism of type i ifns. using reporter assays, we discovered that viral infection induced ...201323150165
recombinant vp1 protein expressed in pichia pastoris induces protective immune responses against ev71 in mice.human enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease and is also associated with serious neurological diseases in children. currently, there are no effective antiviral drugs or vaccines against ev71 infection. vp1, one of the major immunogenic capsid proteins of ev71, is widely considered to be the candidate antigen for an ev71 vaccine. in this study, vp1 of ev71 was expressed as a secretory protein with an n-terminal histidine tag in the methylotrophi ...201323159634
a new treatment for neurogenic inflammation caused by ev71 with cr2-targeted complement inhibitor.enterovirus 71 (ev71), one of the most important neurotropic evs, has caused death and long-term neurological sequelae in hundreds of thousands of young children in the asia-pacific region in the past decade. the neurological diseases are attributed to infection by ev71 inducing an extensive peripheral and central nervous system (cns) inflammatory response with abnormal cytokine production and lymphocyte depletion induced by ev71 infection. in the absence of specific antiviral agents or vaccines ...201223173749
cleavage of interferon regulatory factor 7 by enterovirus 71 3c suppresses cellular responses.enterovirus 71 (ev71) is a positive-stranded rna virus which is capable of inhibiting innate immunity. among virus-encoded proteins, the 3c protein compromises the type i interferon (ifn-i) response mediated by retinoid acid-inducible gene-i (rig-i) or toll-like receptor 3 that activates interferon regulatory 3 (irf3) and irf7. in the present study, we report that enterovirus 71 downregulates irf7 through the 3c protein, which inhibits the function of irf7. when expressed in mammalian cells, the ...201323175366
ribavirin-resistant mutants of human enterovirus 71 express a high replication fidelity phenotype during growth in cell culture.it has been shown in animal models that ribavirin-resistant poliovirus with a g64s mutation in its 3d polymerase has high replication fidelity coupled with attenuated virulence. here, we describe the effects of mutagenesis in the human enterovirus 71 (hev71) 3d polymerase on ribavirin resistance and replication fidelity. seven substitutions were introduced at amino acid position 3d-g64 of a hev71 full-length infectious cdna clone (26m). viable clone-derived virus populations were rescued from th ...201323175376
development of a coxsackievirus a16 neutralization assay based on pseudoviruses for measurement of neutralizing antibody titer in human serum.serum neutralizing antibody titers are indicative of protective immunity against coxsackievirus a16 (cv-a16) and enterovirus 71 (ev71), the two main etiological agents of hand, foot and mouth disease (hfmd), and provide the basis for evaluating vaccine efficacy. the current cv-a16 neutralization assay based on inhibition of cytopathic effects requires manual microscopic examination, which is time-consuming and labor-intensive. in this study, a high-throughput neutralization assay was developed b ...201323178532
novel marker for recombination in the 3'-untranslated region of members of the species human enterovirus a.human enterovirus a (hev-a) is a species in the genus enterovirus. viruses belonging to this species are often responsible for hand, foot and mouth disease and associated acute neurological disease. studies of the 3' untranslated region (utr) of human enterovirus 71 (hev71) revealed a possible role in virus replication. we compared the 3'-utrs of all members of hev-a and confirmed the presence of a secondary structure comprising three stem-loop domains (slds). sld-z is situated closest to the st ...201323178966
[infection mechanism of enterovirus 71].identification of a specific viral receptor is important for understanding the virus infection mechanism. i identified p-selectin glycoprotein ligand-1 (psgl-1) as one of the functional receptors for enterovirus 71 (ev71), a pathogen that causes hand, foot, and mouth disease. psgl-1, which belongs to the sialomucin family, is a transmembrane protein mainly expressed on leukocytes. tyrosine sulfation in the n-terminal region of psgl-1 is critical for psgl-1's capacity to bind ev71. the identifica ...201223189832
[multiple viral transmission chains of enterovirus 71 co-circulated in jilin province during 2009-2010].to analyze the genetic characterization of enterovirus type71 (ev71) associated with hand foot and mouth disease (hfmd) epidemics in jilin province, during 2009-2010.201223189842
differential apoptosis gene expressions of rhabdomyosarcoma cells in response to enterovirus 71 infection.enterovirus 71 (ev71) infection can induce the apoptosis of infected cells. the aim of this study is to explore the effect of ev71 infection on apoptosis mechanisms in virus-infected human rhabdomyosarcoma (rd) cells.201223191987
rapid and sensitive identification of rna from the emerging pathogen, coxsackievirus a6.hand, foot and mouth disease (hfmd) is caused by members of the family picornaviridae in the genus enterovirus. it has been reported that coxsackievirus a6 (cva6) infections are emerging as a new and major cause of epidemic hfmd. sporadic hfmd cases positive for cva6 were detected in the mainland of china in recent years. to strengthen the surveillance of cva6 infections and outbreak control, the clinical diagnosis is urgently needed to distinguish the cva6 infection disease from other infection ...201223194501
enterovirus 71-associated hand, foot, and mouth disease, southern vietnam, 2011.we prospectively studied 3,791 children hospitalized during 2011 during a large outbreak of enterovirus 71-associated hand, foot, and mouth disease in vietnam. formal assessment of public health interventions, use of intravenous immunoglobulin and other therapies, and factors predisposing for progression of disease is needed to improve clinical management.201223194699
characterization of a novel monoclonal antibody reactive against the n-terminal region of enterovirus 71 vp1 capsid protein.hand, foot and mouth disease (hfmd) is a viral infectious disease caused by human enterovirus a, particularly enterovirus 71 (ev71) and coxsackievirus 16 (ca16) serotypes, with ev71 infection associated with severe neurological complications and mortality. lots of attention has been placed on elucidating viral epitopes, which is useful for ev71 viral research. in this study, a murine monoclonal antibody (mab 4) specific for ev71 was generated and mapped to target the n-terminal region of vp1 cap ...201323219932
lncrna expression signatures in response to enterovirus 71 infection.outbreaks of hand, foot, and mouth disease caused by enterovirus 71 (ev71) have become considerable threats to the health of infants and young children. to identify the cellular long noncoding rnas (lncrnas) involved in the host response to ev71 infection, we performed comprehensive lncrna and mrna profiling in ev71-infected rhabdomyosarcoma cells through microarray. we observed the differential expression of more than 4800 lncrnas during infection. further analysis showed 160 regulated enhancer ...201323220233
encephalitis and postinfectious encephalitis.encephalitis and postinfectious encephalitis represent two important conditions for the neurologist, both in terms of their presentations as neurologic emergencies and their potential to cause death or serious neurologic impairment. this article reviews the major infectious and noninfectious causes of encephalitis and discusses postinfectious encephalitis as an indirect effect of systemic illness.201223221841
infectious myelopathies.infections and secondary inflammatory changes play an important role in spine pathology leading to myelopathy or myelitis. to achieve optimal clinical outcomes and accurate prognosis, physicians must promptly recognize these disorders. this review provides a contemporary overview of the major pathogens known to cause myelopathic symptoms and focuses on unique clinical syndromes and signs to aid the differential diagnosis and further workup. this article will help neurologists to consider infecti ...201223221845
immunological and biochemical characterization of coxsackie virus a16 viral particles.coxsackie virus a16 (cva16) infections have become a serious public health problem in the asia-pacific region. it manifests most often in childhood exanthema, commonly known as hand-foot-and-mouth disease (hfmd). there are currently no vaccine or effective medical treatments available.201223226233
[methyl 3, 4-dihydroxyphenylacetate prevents enterovirus 71 proliferation in rhabdomyosarcoma cells].this article presented the inhibitory activity of methyl 3, 4-dihydroxyphenylacetate on the enterovirus 71 (ev71) infection. the ev71 vp1 capsid protein expression levels were analyzed with western blotting. results revealed that the compound is able to inhibit ev71 replication in rhabdomyosarcoma (rd) cells. after being incubated with the compound at a concentration of 0.01 microg x microl(-1) for 48 h, the level of ev71 vp1 mrna in rd cells decreased by (76.83 +/- 2.47)%. the cytotoxic activit ...201223227560
epidemiology and etiological characteristics of hand, foot and mouth disease in huizhou city between 2008 and 2011.to study epidemiological features and etiological characteristics of hand, foot and mouth disease (hfmd), 42,012 cases were investigated from april 2008 to december 2011 in huizhou, china. the average incidence rate was 21.16 per 10,000. the highest peak of hfmd incidence was detected between april and july each year, accounting for 55.93 % of all reported cases; another peak occurred in october through december, accounting for 24.17 % of the cases. of the reported cases, 89.75 % were in childre ...201323229012
progress on the research and development of human enterovirus 71 (ev71) vaccines.enterovirus 71 (ev71) infections, which can cause severe complications, have become one of the serious public health issues in the western pacific region and china. to date, a number of pharmaceutical companies and institutes have initiated the research and development of ev71 vaccines as a countermeasure. as is the case with innovative vaccine development, there are several critical bottlenecks in ev71 vaccine development that must be overcome before the clinical trials, including the selection ...201323247645
human enterovirus 71 strains in the background population and in hospital patients in finland.human enterovirus 71 (hev71) is a common cause of severe outbreaks of hand-foot- and mouth disease, aseptic meningitis and encephalitis in asian populations but has not caused such epidemics in all populations.201323261080
antiviral drug discovery for the treatment of enterovirus 71 infections.enterovirus 71 (ev71) is a small, positive-sense, single-stranded rna virus in the genus enterovirus, family picornavirus. it causes hand, foot and mouth disease in infants and children, which in a small percentage of cases progresses to central nervous system infection, ranging from aseptic meningitis to fatal encephalitis. sporadic cases of ev71 infection occur throughout the world, but large epidemics have occurred recently in southeast asia and china. there are currently no approved vaccines ...201323261847
development and characterization of a stable egfp enterovirus 71 for antiviral screening.enterovirus 71 (ev71) is one of the major causative agents for hand, foot, and mouth disease. there is currently no clinically approved vaccine or antiviral treatment for ev71 infection. to facilitate antiviral drug discovery, we developed an infectious cdna clone of an epidemic strain of ev71 and a stable egfp reporter ev71. the reporter virus was generated by engineering the egfp gene between the 5' untranslated region and vp4 gene of the ev71 genome. vero cells transfected with the cdna clone ...201223267829
[cloning, expression and antigenic analysis of vp1-vp4 gene encoding the structural protein of coxsackie virus a16].to clone and express vp1-vp4 genes encoding the structural proteins of coxsackie virus a16 and analyze the antigenicity of the expressed recombinant proteins.201223268395
evaluation of a direct reverse transcription loop-mediated isothermal amplification method without rna extraction for the detection of human enterovirus 71 subgenotype c4 in nasopharyngeal swab specimens.human enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd) worldwide and has been associated with neurological complications which resulted in fatalities during recent outbreak in asia pacific region. a direct reverse transcription loop-mediated isothermal amplification (direct rt-lamp) assay using heat-treated samples without rna extraction was developed and evaluated for the detection of ev71 subgenotype c4 in nasopharyngeal swab specimens. the analytical ...201223272248
oral immunization of mice using bifidobacterium longum expressing vp1 protein from enterovirus 71.bifidobacterium longum is an attractive candidate for delivering biologically active proteins by the mucosal route due to its non-pathogenic and colonizing properties. enterovirus 71 (ev71) has aroused widespread attention recently due to several epidemics, and great attention should be paid to the fact that there are currently no effective antiviral drugs or vaccines against ev71 infection. in this report, we described a recombinant b. longum that could be used to develop an oral vaccine agains ...201323275129
enterovirus 71-induced neurological disorders in young gerbils, meriones unguiculatus: development and application of a neurological disease model.a reliable disease model mimicking enterovirus 71 (ev71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to ev71 infection after they reach the age of 6 days. in this study, 21-day-old gerbils inoculated intraperitoneally (ip) with a non mouse-adapted ev71 strain developed neurological lesion-related s ...201223284845
enterovirus 71 infection increases expression of interferon-gamma-inducible protein 10 which protects mice by reducing viral burden in multiple tissues.enterovirus 71 (ev71) infection has induced fatal encephalitis in thousands of young children in the asia-pacific region over the last decade. ev71 infection continues to cause serious problems in areas with outbreaks, because vaccines and antiviral therapies are not available. lymphocytes are present in the brains of infected patients and mice, and they protect mice from infection by decreasing the viral burden. the chemokines responsible for recruiting lymphocytes to infected organs are yet to ...201323288420
[etiological detection of severe hand-food-mouth disease and related genetic characteristics of enterovirus type 71 infection in beijing, 2010].to study the etiological detection on samples from severe hand-foot-mouth disease (hfmd) cases and the genetic characteristics of enterovirus type 71 (ev71) isolates from severe patients in beijing, 2010.201223290804
[typing and identification of non-polio enterovirus from acute flaccid paralysis cases in ningxia, 1997-2011].to identify the serotype of 73 non-polio enterovirus (npev) strains from acute flaccid paralysis (afp) cases in ningxia province, during 1997 - 2011.201223290905
rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: evaluation of antiviral efficacy in a murine infection model.enterovirus-71 (ev71) infections can cause life-threatening diseases with neurological symptoms. currently, no direct targeting antivirals are available to combat severe ev71 infection. rupintrivir (ag7088) is a compound originally designed for rhinovirus 3c protease. previous computational analyses by us and crystallography studies by others suggested that rupintrivir is also a high affinity inhibitor to ev71 3c. thus, we aimed to further evaluate its anti-ev71 activity in vivo at clinically ac ...201323295352
quinacrine impairs enterovirus 71 rna replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.since the 1980s, epidemics of enterovirus 71 (ev71) and other enteroviruses have occurred in asian countries and regions, causing a wide range of human diseases. no effective therapy is available for the treatment of these infections. internal ribosome entry sites (iress) are indispensable for the initiation of translation in enteroviruses. several cellular factors, as well as the ribosome, are recruited to the conserved ires during this process. quinacrine intercalates into the rna architecture ...201323301007
functional comparison of scarb2 and psgl1 as receptors for enterovirus 71.human scavenger receptor class b, member 2 (scarb2), and p-selectin glycoprotein ligand-1 (psgl1) have been identified to be the cellular receptors for enterovirus 71 (ev71). we compared the ev71 infection efficiencies of mouse l cells that expressed scarb2 (l-scarb2) and psgl1 (l-psgl1) and the abilities of scarb2 and psgl1 to bind to the virus. l-scarb2 cells bound a reduced amount of ev71 compared to l-psgl1 cells. however, ev71 could infect l-scarb2 cells more efficiently than l-psgl1 cells. ...201323302872
strategies to develop antivirals against enterovirus 71.enterovirus 71 (ev71) is an important human pathogen which may cause severe neurological complications and death in children. the virus caused several outbreaks in the asia-pacific region during the past two decades and has been considered a significant public health problem in the post-poliovirus eradication era. unlike poliovirus, there is no effective vaccine or approved antivirals against ev71. to explore anti-ev71 agents therefore is of vital importance. several strategies have been employe ...201323339605
risk factors for neurologic complications of hand, foot and mouth disease in the republic of korea, 2009.in 2009, the first outbreak of hand, foot and mouth disease (hfmd) or herpangina (hp) caused by enterovirus 71 occurred in the republic of korea. this study inquired into risk factors associated with complications of hfmd or hp. a retrospective medical records review was conducted on hfmd or hp patients for whom etiologic viruses had been verified in 2009. one hundred sixty-eight patients were examined for this investigation. eighty patients were without complications while 88 were accompanied b ...201323341722
excretion of enterovirus 71 in persons infected with hand, foot and mouth disease.hand, foot and mouth disease (hfmd) is a common illness in young children. it also can be seen in adults occasionally. enterovirus 71 (ev71), a pathogen that causes not only hfmd but also neurological complications and even death, has caused many hfmd outbreaks in china. however, till now the data about the duration of ev71 shedding is very limited.201323343115
breastfeeding, previous epstein-barr virus infection, enterovirus 71 infection, and rural residence are associated with the severity of hand, foot, and mouth disease.severe hand, foot, and mouth disease (hfmd) is likely to develop critical complications such as brainstem encephalitis, acute pulmonary edema, and circulatory failure, which cause child mortality during outbreaks. this study aims to investigate factors that predict the severity of hfmd. one hundred sixteen in-patient children with severe hfmd and 202 with mild hfmd were retrospectively enrolled. potential factors were collected for each child including sex, age, residence, modes of delivery, bir ...201323344210
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