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