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performance of reversed transcription loop-mediated isothermal amplification technique detecting ev71: a systematic review with meta-analysis.human enterovirus 71 (ev71) is the major etiological agent of hand, foot and mouth disease (hfmd), which is a common infectious disease in young children. studies in the past have shown that reversed transcription loop-mediated isothermal amplification (rt-lamp) was a rapid approach for the detection of ev71 in hfmd. this meta-analysis study is to evaluate the diagnostic role of rt-lamp in detecting ev71 infection. a comprehensive literature research of pubmed, embase, wan fang data, and chinese ...201424815384
association of viral replication capacity with the pathogenicity of enterovirus 71.enterovirus 71 (ev71) is a major cause of hand-foot-and-mouth disease, which is associated with fatal neurological disease. the mechanism of ev71 pathogenesis remains obscure. we compared the replication capacity of the severe and mild enterovirus 71 isolates. the replication kinetics of ev71 in rd cells and icr mice was determined by qrt-pcr. the lung, muscular, brain, intestine tissues were used for histopathological and immunohistochemical assays. the growth curves of ev71 strains in rd cells ...201424792876
enterovirus 71 virus propagation and purification.since its discovery in 1969, enterovirus 71 (ev71) has emerged as a serious worldwide health threat. this member of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. this is the propagation and purification procedure to produce infectious virion.201427547789
genetic polymorphism of ccl2-2510 and susceptibility to enterovirus 71 encephalitis in a chinese population.the study was performed in 36 chinese patients with enterovirus 71 (ev71) encephalitis and 141 patients with ev71-related hand, foot and mouth disease (hfmd) without encephalitis. genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism technique. patients with ev71 encephalitis had a significantly higher frequency of the ccl2-2510gg genotypes when compared to patients with ev71-related hfmd without encephalitis (66.7% vs. 41.8%, p=0.028). the frequency of cc ...201424788844
mutations in the non-structural protein region contribute to intra-genotypic evolution of enterovirus 71.clinical manifestations of enterovirus 71 (ev71) range from herpangina, hand-foot-and-mouth disease (hfmd), to severe neurological complications. unlike the situation of switching genotypes seen in ev71 outbreaks during 1998-2008 in taiwan, genotype b5 was responsible for two large outbreaks in 2008 and 2012, respectively. in china, by contrast, ev71 often persists as a single genotype in the population and causes frequent outbreaks. to investigate genetic changes in viral evolution, complete ev ...201424766641
in vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate oligonucleotide.enterovirus 71 (ev71) is a highly infectious virus that is a major cause of hand, foot, and mouth disease (hfmd), which can lead to severe neurological complications. currently, there is no effective therapy against ev71. five antisense oligodeoxynucleotides targeting the 5'-terminal conserved domain of the viral genome were designed using a method based on multiple predicted target mrna structures. they were then screened for anti-ev71 activity in vitro based on their ability to inhibit an ev71 ...201424756344
[histopathological changes in ev71-infected mouse model:a transmission electron microscopic study].to document ultrastructural changes of brain, spinal cord, skeletal muscle, jejunum and lung of ev71 infection mouse model, and to explore the myotropism and pathogenesis of ev71 in nervous system.201424742571
animal models of enterovirus 71 infection: applications and limitations.human enterovirus 71 (ev71) has emerged as a neuroinvasive virus that is responsible for several outbreaks in the asia-pacific region over the past 15 years. appropriate animal models are needed to understand ev71 neuropathogenesis better and to facilitate the development of effective vaccines and drugs. non-human primate models have been used to characterize and evaluate the neurovirulence of ev71 after the early outbreaks in late 1990s. however, these models were not suitable for assessing the ...201424742252
severe enterovirus type 71 nervous system infections in children in the shanghai region of china: clinical manifestations and implications for prevention and care.severe outbreaks of enterovirus 71 (ev71) have been on the rise in the western pacific region, including in china since 2007. we describe features of pediatric patients admitted with severe disease ev71 to a tertiary care hospital during the 2010 ongoing outbreak in the shanghai region.201424732390
update on enterovirus 71 infection.human enterovirus type 71 (ev71) has emerged as a major cause of viral encephalitis in children worldwide. the identified ev71 receptors provide useful information for understanding ev71replication and tissue tropism. host factors interact with the internal ribosome entry site (ires) of ev71 to regulate viral translation. however, the specific molecular features of the ev71 genome that determine virulence remain unclear. the ev71 capsid protein vp1 region might contribute to virulence and neurot ...201424727707
estimation of contamination sources of human enteroviruses in a wastewater treatment and reclamation system by pcr-dgge.a polymerase chain reaction-denaturing gradient gel electrophoresis (pcr-dgge) method was employed to estimate the contamination sources of human enteroviruses and understand how their dominant strains vary in a wastewater treatment and reclamation system consisting of sewage collection, wastewater treatment with membrane bioreactor and open lakes for reclaimed water storage and reuse. after pcr-dgge using a selected primer set targeting enteroviruses, phylogenetic analysis of acquired enterovir ...201424715657
detection of enterovirus 71 gene from clinical specimens by reverse-transcription loop-mediated isothermal amplification.the objective of this study was to develop a sensitive, specific and rapid approach to diagnose hand foot and mouth disease (hfmd) for an early treatment by using loop-mediated isothermal amplification (lamp) technique.201424713896
[the exploration of the role of angiopoietin-2 in pulmonary edema induced by ev71 infection].to observe the clinic character of pulmonary edema (pe) induced by enterovirus 71 (ev71) and the change in angiopoietin-2 (ang-2), and to explore the correlation between ang-2 and pe.201424696919
[an investigation on a case of hand-foot-mouth disease caused by coxsackie-virus a6 associated with a vaccine-derived poliovirus co-infection].to identify the pathogen and characteristics on a case of hand-foot-mouth disease (hfmd) caused by coxsackie-virus a6 (ca6) associated with vaccine-derived poliovirus (vdpv) co-infection.201424685040
the multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating ires-dependent translation of viral proteins.the activation of erk and p38 signal cascade in host cells has been demonstrated to be essential for picornavirus enterovirus 71 (ev71) replication and up-regulation of virus-induced cyclooxygenase-2 (cox-2)/prostaglandins e2 (pge2) expression. the aim of this study was to examine the effects of sorafenib, a clinically approved anti-cancer multi-targeted kinase inhibitor, on the propagation and pathogenesis of ev71, with a view to its possible mechanism and potential use in the design of therapy ...201424680956
prenylated benzoylphloroglucinols and xanthones from the leaves of garcinia oblongifolia with antienteroviral activity.an acetone extract of the leaves of garcinia oblongifolia showed antiviral activity against enterovirus 71 (ev71) using a cytopathic effect inhibition assay. bioassay-guided fractionation yielded 12 new prenylated benzoylphloroglucinols, oblongifolins j-u (1-12), and five known compounds. the structures of 1-12 were elucidated by spectroscopic analysis including 1d- and 2d-nmr and mass spectrometry methods. the absolute configurations were determined by a combination of a mosher ester procedure ...201424679044
phenotypic and genotypic characteristics of novel mouse cell line (nih/3t3)-adapted human enterovirus 71 strains (ev71:tllm and ev71:tllmv).since its identification in 1969, enterovirus 71 (ev71) has been causing periodic outbreaks of infection in children worldwide and most prominently in the asia-pacific region. understanding the pathogenesis of enterovirus 71 (ev71) is hampered by the virus's inability to infect small animals and replicate in their derived in vitro cultured cells. this manuscript describes the phenotypic and genotypic characteristics of two selected ev71 strains (ev71:tllm and ev71:tllmv), which have been adapted ...201424671184
protection against lethal enterovirus 71 challenge in mice by a recombinant vaccine candidate containing a broadly cross-neutralizing epitope within the vp2 ef loop.human enterovirus 71 (ev71) is the main causative agent of hand, foot, and mouth disease (hfmd) and is associated with several severe neurological complications in the asia-pacific region. here, we evaluated that while passive transfer of neutralizing monoclonal antibody (nmab) against the vp2 protein protect against lethal ev71 infection in balb/c mice. protective nmab were mapped to residues 141-155 of vp2 by peptide elisa. high-resolution structural analysis showed that the epitope is part of ...201424669278
quality control and evaluation of vaccines in china.i was born in luoyang in 1963, a city in china with thousands of years' history. the city is the eastern starting point of the silk road (bc 206-260 ad), a famous and long trade route in human history. living in this ancient city, i grew up under the influence and impact of chinese traditional culture. when i was a teenager, i once read a book "yellow emperor's inner canon" (huang di nei jing, written about 5th century bc), which is the oldest extant classic of traditional chinese medicine. i wa ...201424663039
enterovirus 71 related severe hand, foot and mouth disease outbreaks in south-east asia: current situation and ongoing challenges. 201424652348
sybr green real-time pcr for the detection of all enterovirus-a71 genogroups.enterovirus a71 (ev-a71) has recently become an important public health threat, especially in south-east asia, where it has caused massive outbreaks of hand, foot and mouth disease every year, resulting in significant mortality. rapid detection of ev-a71 early in outbreaks would facilitate implementation of prevention and control measures to limit spread. real-time rt-pcr is the technique of choice for the rapid diagnosis of ev-a71 infection and several systems have been developed to detect circ ...201424651608
association of ip-10 gene polymorphism with susceptibility to enterovirus 71 infection.enterovirus 71 (ev71) often causes large outbreaks of diseases among children worldwide and its pathogenesis remains unclear. the aim of the present study was to investigate the association between interferon-inducible protein 10 (ip-10) polymorphism in children with ev71 infection. polymerase chain reaction (pcr) and restriction fragment length polymorphism (rflp) were performed to analyze the gene polymorphisms of ip-10 (-1596c/t) in 58 ev71-infected and 48 control patients. the results showed ...201324648959
clinical evaluation for batch consistency of an inactivated enterovirus 71 vaccine in a large-scale phase 3 clinical trial.the demonstration of batch-to-batch consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. this is a post-hoc analysis aimed to provide more solid evidence on the immunogenicity and consistency of 3 consecutive batches of a novel inactivated enterovirus 71 (ev71) vaccine. in total 10 245 healthy chinese children aged 6-35 months had been recruited and randomized to receive one of 3 batches of ev71 vaccine or placebo according to a ...201424633366
a booster dose of an inactivated enterovirus 71 vaccine in chinese young children: a randomized, double-blind, placebo-controlled clinical trial.a significant waning of enterovirus 71 (ev71) antibody titer after priming immunization with an inactivated ev71 vaccine implied the potential need for a booster dose.201424625805
cell surface vimentin is an attachment receptor for enterovirus 71.enterovirus 71 (ev71) is a highly transmissible pathogenic agent that causes severe central nervous system diseases in infected infants and young children. here, we reported that ev71 vp1 protein could bind to vimentin intermediate filaments expressed on the host cell surface. soluble vimentin or an antibody against vimentin could inhibit the binding of ev71 to host cells. accompanied with the reduction of vimentin expression on the cell surface, the binding of ev71 to cells was remarkably decre ...201424623428
attenuation of human enterovirus 71 high-replication-fidelity variants in ag129 mice.in a screen for ribavirin resistance, a novel high-fidelity variant of human enterovirus 71 (ev71) with the single amino acid change l123f in its rna-dependent rna polymerase (rdrp or 3d) was identified. based on the crystal structure of ev71 rdrp, l123 locates at the entrance of the rna template binding channel, which might form a fidelity checkpoint. ev71 rdrp-l123f variants generated less progeny in a guanidine resistance assay and virus populations with lower mutation frequencies in cell cul ...201424623423
a polymorphism in melanoma differentiation-associated gene 5 may be a risk factor for enterovirus 71 infection.enterovirus 71 (ev71) infection has a wide variety of clinical manifestations, from no symptoms to fatal disease. host immune response may be a determinant of disease severity. we investigated the association of polymorphisms in three pattern recognition receptor (prr) genes-toll-like receptor 3 (tlr3) (rs3775291), retinoic acid-inducible gene i (rig-i) (rs10813831) and melanoma differentiation-associated gene 5 (mda5) (rs1990760)-with the severity of ev71 infection. polymorphisms of candidate g ...201424621100
development of enterovirus 71 vaccines: from the lab bench to phase iii clinical trials.the widespread epidemics of enterovirus 71 (ev71) seriously affected the western pacific region. young children, especially those younger than 3 years are the most susceptible population to the ev71-associated diseases. several asian countries have begun to focus on the research and development of ev71 vaccines. five inactivated whole-virus ev71 candidate vaccines (three were manufactured in mainland china based on a c4 genotype strain, one in taiwan based on a b4 genotype strain and one in sing ...201424621093
the molecule of dc-sign captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection.enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease that occurs in young children. neither antiviral agents nor vaccines are available for efficiently combating viral infection. study of ev71-host interplay is important for understanding viral infection and developing strategies for prevention and therapy. here the interactions of ev71 with human dendritic cells were analyzed.201424620896
serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (hev) 71. in 91 severe or mild hev 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. serum cytokines including type 1 t helper (th1) cytokines: interleukin (il)-2, interferon-gamma (ifn-γ), il-12, and il-18, type 1 t helper (th2) cytokines: il-4, il-10, il-13, proinflammatory cytokines: il-1α, il-1β, il-6, il-8, il-17, ...201424619468
genetic polymorphism of ccl2-2518, cxcl10-201, il8+781 and susceptibility to severity of enterovirus-71 infection in a chinese population.the goal of this study was to examine the relationship between ccl2-2518a/g, cxcl10-201a/g, and il8+781c/t gene polymorphism and severity of enterovirus 71 (ev71) infection in a chinese population.201424609754
[seroepidemiology and molecular epidemiology of enterovirus type 71 in the world and the russian federation].a review of recent publications on epidemiology and seroepidemiology of enterovirus type 71 in various regions of the world and authors' own results of study of seroepidemiology and molecular epidemiology of ev71 in russia are presented.201424605685
cell and tissue tropism of enterovirus 71 and other enteroviruses infections.enterovirus 71 (ev71) is a member of picornaviridae that causes mild and self-limiting hand, foot, and mouth disease (hfmd). however, ev71 infections can progress to polio-like paralysis, neurogenic pulmonary edema, and fatal encephalitis in infants and young children. large ev71 outbreaks have been reported in taiwan, china, japan, malaysia, singapore, and australia. this virus is considered a critical emerging public health threat. ev71 is an important crucial neurotropic enterovirus for which ...201424602216
molecular comparison and evolutionary analyses of vp1 nucleotide sequences of new african human enterovirus 71 isolates reveal a wide genetic diversity.most circulating strains of human enterovirus 71 (ev-a71) have been classified primarily into three genogroups (a to c) on the basis of genetic divergence between the 1d gene, which encodes the vp1 capsid protein. the aim of the present study was to provide further insights into the diversity of the ev-a71 genogroups following the recent description of highly divergent isolates, in particular those from african countries, including madagascar. we classified recent ev-a71 isolates by a large comp ...201424598878
antiviral activity of hederasaponin b from hedera helix against enterovirus 71 subgenotypes c3 and c4a.enterovirus 71 (ev71) is the predominant cause of hand, foot and mouth disease (hfmd). the antiviral activity of hederasaponin b from hedera helix against ev71 subgenotypes c3 and c4a was evaluated in vero cells. in the current study, the antiviral activity of hederasaponin b against ev71 c3 and c4a was determined by cytopathic effect (cpe) reduction method and western blot assay. our results demonstrated that hederasaponin b and 30% ethanol extract of hedera helix containing hederasaponin b sho ...201424596620
an atypical winter outbreak of hand, foot, and mouth disease associated with human enterovirus 71, 2010.to analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (hfmd) outbreak caused by enterovirus 71 in linyi city, shandong province, china during november 30 to december 28, 2010.201424589030
comparative study of the immunogenicity in mice and monkeys of an inactivated ca16 vaccine made from a human diploid cell line.the coxsackie a16 virus (ca16), along with enterovirus 71 (ev71), is a primary pathogen that causes hand, foot, and mouth disease (hfmd). to control hfmd, ca16, and ev71 vaccines are needed. in this study, an experimental inactivated ca16 vaccine was prepared using human diploid cells, and the vaccine's immunogenicity was analyzed in mice and rhesus monkeys. the results showed that the neutralizing antibody was developed in a dose-dependent manner, and was sustained for 70 days with an average g ...201424583556
update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine.enterovirus 71 (ev71) is a neurotropic human pathogen that is the causative agent of hand foot and mouth disease (hfmd), herpangina and brain stem encephalitis. recurrent ev71 epidemics of various scales have occurred in the asia-pacific region. several specific cell surface molecules serve as the receptors for ev71. identification of the receptors is an important step to understand ev71 disease. cytokines, lymphocytes and monocytes contribute significantly to ev71 pathogenesis. the interaction ...201424579906
[identification and characterization of enterovirus 71 isolated in yunnan province].identification and characterization of eight enterovirus 71 samples isolated from yunnan province.201324579470
risk factors for critical disease and death from hand, foot and mouth disease.there has been a high mortality and morbidity rate of critical and fatal patients from hand, foot and mouth disease (hfmd) in china in recent. causes for development of critical and fatal disease remain unclear.201424577041
an inactivated enterovirus 71 vaccine in healthy children.enterovirus 71 (ev71) is a major cause of hand, foot, and mouth disease in children and may be fatal. a vaccine against ev71 is needed.201424571755
efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in china.enterovirus 71 (ev71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. this phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an ev71 vaccine.201424571754
inhibition of mir-146a prevents enterovirus-induced death by restoring the production of type i interferon.there are no antivirals or vaccines available to treat enterovirus 71 (ev71) infections. although the type i interferon response, elicited upon virus infection, is critical to establishing host antiviral innate immunity, ev71 fails to induce this response efficiently. here we provide new insights into potential anti-ev71 therapy by showing that neutralization of ev71-induced mir-146a prevents death in mice by restarting the production of type i interferon. ev71 infection upregulates mir-146a, wh ...201424561744
development of antiviral agents toward enterovirus 71 infection.enterovirus 71 (ev71) infection remains a public health problem at a global level, particularly in the asia-pacific region. the infection normally manifests as hand-foot-mouth disease; however, it is capable of developing into potentially fatal neurological complications. there is currently no approved vaccine or antiviral substance available for the prevention or treatment of ev71 infection. this paper, thus, reviews efforts to develop or discover synthetic as well as naturally occurring compou ...201524560700
epidemiology and seroepidemiology of human enterovirus 71 among thai populations.human enterovirus 71 (ev71) is an important pathogen caused large outbreaks in asian-pacific region with severe neurological complications and may lead to death in young children. understanding of the etiological spectrum and epidemic changes of enterovirus and population's immunity against ev71 are crucial for the implementation of future therapeutic and prophylactic intervention.201424548776
overall codon usage pattern of enterovirus 71.hand, foot, and mouth disease (hfmd) is a systemic illness in children and is usually caused by enterovirus 71 (ev71). to provide new insights into the genetic features of ev71 and the relationship between the overall codon usage pattern of this virus and that of humans, values for relative synonymous codon usage (rscu), effective number of codons (enc), codon adaptation index (cai), and nucleotide composition were calculated and analyzed. the relationship between enc values and (g+c)₃% suggests ...201424535860
recent developments in antiviral agents against enterovirus 71 infection.enterovirus 71 (ev-71) is the main etiological agent of hand, foot and mouth disease (hfmd). recent ev-71 outbreaks in asia-pacific were not limited to mild hfmd, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. the absence of licensed therapeutics for clinical use has intensified research into anti-ev-71 development. this review highlights the potential antiviral agents targetin ...201424521134
construction and characterization of a recombinant human adenovirus type 3 vector containing two foreign neutralizing epitopes in hexon.the "antigen capsid-incorporation" strategy has been developed for adenovirus-based vaccines in the context of several diseases. exogenous antigenic peptides incorporated into the adenovirus capsid structure can induce a robust and boosted antigen-specific immune response. recently, we sought to generate a multivalent adenovirus type 3 (ad3) vaccine vector by incorporating multiple epitopes into the major adenovirus capsid protein, hexon. in the present study, a multivalent recombinant ad3 vacci ...201424518297
phylogenetic analysis of the vp1 gene of enterovirus 71 in guangzhou during the high occurrence period of 2008.an outbreak of hand, foot, and mouth disease (hfmd) in guangzhou in 2008 affected over 10,000 children and resulted in high hospital admission rates. to investigate the molecular epidemiological pattern of ev71 infections in guangzhou, throat swab samples were collected from 102 children clinically diagnosed with hfmd from may to july of 2008 in guangzhou. partial vp1 (virus protein 1) fragments of enterovirus 71 (ev71) isolates were sequenced, and used alongside ev71 sequences entered in genban ...201424515837
more-powerful virus inhibitors from structure-based analysis of hev71 capsid-binding molecules.enterovirus 71 (hev71) epidemics in children and infants result mainly in mild symptoms; however, especially in the asia-pacific region, infection can be fatal. at present, no therapies are available. we have used structural analysis of the complete virus to guide the design of hev71 inhibitors. analysis of complexes with four 3-(4-pyridyl)-2-imidazolidinone derivatives with varying anti-hev71 activities pinpointed key structure-activity correlates. we then identified additional potentially bene ...201424509833
time series analysis of hand-foot-mouth disease hospitalization in zhengzhou: establishment of forecasting models using climate variables as predictors.large-scale outbreaks of hand-foot-mouth disease (hfmd) have occurred frequently and caused neurological sequelae in mainland china since 2008. prediction of the activity of hfmd epidemics a few weeks ahead is useful in taking preventive measures for efficient hfmd control.201424498221
effect of all-trans-retinoic acid on enterovirus 71 infection in vitro.our previous studies have shown that vitamin a (va) status is associated with antiviral immunity and pathogenic conditions in enterovirus 71 (ev71)-infected children. in the present study, we established an in vitro model to investigate the effects and potential mechanism of the antiviral activity of va. human monocytic u937 cells were cultured in vitro and infected with ev71. all-trans-retinoic acid (atra), the active metabolite of va, and ro 41-5253, a retinoic acid receptor-α (rar-α) antagoni ...201424495389
polyc-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 rna in membrane-associated complex to facilitate viral replication.enterovirus 71 (ev71) is one causative agent of hand, foot, and mouth disease (hfmd), which may lead to severe neurological disorders and mortality in children. ev71 genome is a positive single-stranded rna containing a single open reading frame (orf) flanked by 5'-untranslated region (5'utr) and 3'utr. the 5'utr is fundamentally important for virus replication by interacting with cellular proteins. here, we revealed that poly(c)-binding protein 1 (pcbp1) specifically binds to the 5'utr of ev71. ...201424489926
hand, foot, and mouth disease in china, 2008-12: an epidemiological study.hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. increasingly, the disease has a substantial burden throughout east and southeast asia. to better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in china on the basis of enhanced surveillance.201424485991
neutralizing antibodies can initiate genome release from human enterovirus 71.antibodies were prepared by immunizing mice with empty, immature particles of human enterovirus 71 (ev71), a picornavirus that causes severe neurological disease in young children. the capsid structure of these empty particles is different from that of the mature virus and is similar to "a" particles encountered when picornaviruses recognize a potential host cell before genome release. the monoclonal antibody e18, generated by this immunization, induced a conformational change when incubated at ...201424469789
enterovirus 71 infection-associated acute flaccid paralysis: a case series of long-term neurologic follow-up.the authors undertook long-term neurologic outcomes of 27 patients aged 0 to 15 years with enterovirus 71-related acute flaccid paralysis from june 1998 to july 2012. motor function outcome was graded from class i (complete recovery) to class v (permanent paralytic limbs). twelve of 20 patients (60%) who received intravenous immunoglobulin for treatment of acute flaccid paralysis had motor function outcomes in classes iii to v. the median duration of follow-up was 6 months, during which time 7 o ...201424453152
a novel finding for enterovirus virulence from the capsid protein vp1 of ev71 circulating in mainland china.enterovirus 71 (ev71) is a neurotropic virus that causes various clinical manifestations in young children, ranging from asymptomatic to fatal. different pathotypes of ev71 notably differ in virulence. several virulence determinants of ev71 have been predicted. however, these reported virulence determinants could not be used to identify the ev71 strains of subgenotype c4, which mainly circulate in china. in this study, vp1 sequences of 37 ev71 strains from severe cases (sc-ev71) and 192 ev71 str ...201424442718
interleukin-8 is elevated in severe hand, foot, and mouth disease.enterovirus 71 (ev71) infections can cause hand, foot, and mouth disease (hfmd), which is a potentially fatal illness in children. epidemics of hfmd are seen every year globally and present an increasing threat to public health worldwide.201424423718
spatio-temporal analysis on enterovirus cases through integrated surveillance in taiwan.severe epidemics of enterovirus have occurred frequently in malaysia, singapore, taiwan, cambodia, and china, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available. the specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data.201424400725
the gene expression profile of peripheral blood mononuclear cells from ev71-infected rhesus infants and the significance in viral pathogenesis.enterovirus 71 (ev71) is the major pathogen responsible for fatal hand, foot and mouth disease (hfmd). our previous work reported on an ev71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (cns) and lungs. this study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (pbmcs) from ev71-infected rhesus monkey infants. the expression of more than 500 functional genes associated with mult ...201424392094
molecular epidemiology of enterovirus 71 infection in the central region of taiwan from 2002 to 2012.enterovirus 71 (ev71), a causative agent of hand, foot, and mouth disease can be classified into three genotypes and many subtypes. the objectives of this study were to conduct a molecular epidemiological study of ev71 in the central region of taiwan from 2002-2012 and to test the hypothesis that whether the alternative appearance of different ev71 subtypes in taiwan is due to transmission from neighboring countries or from re-emergence of pre-existing local strains. we selected 174 ev71 isolate ...201324391812
[analysis of pathogen spectrum of encephalitis/meningitis in northwestern area of china].to learn the characteristics of pathogen spectrum of encephalitis /meningitis in northwestern area of china.201324378133
suramin inhibits ev71 infection.enterovirus-71 (ev71) is one of the major causative reagents for hand-foot-and-mouth disease. in particular, ev71 causes severe central nervous system infections and leads to numerous dead cases. although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. in the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit ev71 p ...201424374150
complete genome sequence of a human enterovirus 71 strain isolated in wuhan, china, in 2010.the complete genome sequence of a human enterovirus 71 strain (ev71/wuhan/3018/2010), which was isolated in wuhan in 2010, was amplified by a reverse transcription-pcr method and sequenced. phylogenetic analysis based on the complete genome sequence classified this strain into subgenogroup a.201324371206
construction of an infectious cdna clone of enterovirus 71: insights into the factors ensuring experimental success.enterovirus 71 (ev 71) is a causative agent of mild hand foot and mouth disease but is capable of causing severe complications in the cns in young children. reverse genetics technology is currently widely used to study the pathogenesis of the virus. the aim of this work was to determine and evaluate the factors which can contribute to infectivity of ev 71 rna transcripts in vitro. two strategies, overlapping rt-pcr and long distance rt-pcr, were employed to obtain the full-length genome cdna clo ...201424361875
the mechanism of translation initiation on type 1 picornavirus iress.picornavirus type 1 iress comprise five principal domains (dii-dvi). whereas dv binds eif4g, a conserved aug in dvi was suggested to stimulate attachment of 43s ribosomal preinitiation complexes, which then scan to the initiation codon. initiation on type 1 iress also requires ires trans-acting factors (itafs), and several candidates have been proposed. here, we report the in vitro reconstitution of initiation on three type 1 iress: poliovirus (pv), enterovirus 71 (ev71), and bovine enterovirus ...201424357634
antigenic and genetic diversity of human enterovirus 71 from 2009 to 2012, taiwan.different subgenogroups of enterovirus 71 (ev-71) have caused numerous outbreaks of hand, foot, and mouth disease worldwide, especially in the asia-pacific region. during the development of a vaccine against ev-71, the genetic and antigenic diversities of ev-71 isolates from taiwan were analyzed by phylogenetic analyses and neutralization tests. the results showed that the dominant genogroups had changed twice, from b to c and from c to b, between 2009 and 2012. the subgenogroup b5 (b5b cluster) ...201324348916
dominant cd4-dependent rna-dependent rna polymerase-specific t-cell responses in children acutely infected with human enterovirus 71 and healthy adult controls.human enterovirus 71 (ev71) is one of the major causes of hand, foot and mouth disease (hfmd), which leads to significant mortality in infected children. a prophylactic vaccine is urgently needed. however, little is known about the protective t-cell immunity in individuals infected with the ev71 virus. in this study, we performed a comprehensive ex vivo interferon-γ elispot analysis in 31 children infected with ev71 as well as in 40 healthy adult controls of the cd4(+) and cd8(+) t-cell response ...201424329688
immunization of n terminus of enterovirus 71 vp4 elicits cross-protective antibody responses.enterovirus 71 (ev71) is major cause of hand, foot and mouth disease. large epidemics of ev71 infection have been recently reported in the asian-pacific region. currently, no vaccine is available to prevent ev71 infection.201324320792
[development of ev71, ca16 and other enterovirus vrial real-time qualitative pcr diagnostic kit].a novel multiplex real-time rt-pcr kit was developed to detect ev71, coxa16 and other human enteroviruses simultaneously with an internal amplification control to avoids false negatives, which used for hand, foot and mouth disease in the clinical diagnosis and epidemiological surveillance.201324319965
[sero-epidemiological analysis for entervirus 71 infection of adults in beijing].to evaluate the enterovirus 71 (ev 71) protective antibody level of health adults people in beijing.201324319947
the nuclear protein sam68 is redistributed to the cytoplasm and is involved in pi3k/akt activation during ev71 infection.nuclear proteins can be triggered to be redistributed to the cytoplasm to assist with ev71 virus replication. this process is frequently involved in cellular signal transduction upon virus infection. in this study, we have demonstrated that a new nuclear protein, 68-kda src-associated in mitosis protein (sam68), was translocated to the cytoplasm and was co-localized with ev71 during virus infection. confocal microscopy and subcellular fractionation assay confirmed that virus 3c protease triggere ...201424316008
peripheral t lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease.inflammatory mediators (i.e. cytokines) play a pivotal role in the regulation of pathophysiological processes during ev71-induced hand, foot and mouth disease (hfmd). different t cell subsets have distinct cytokine secretion profiles, and alteration in the t cell subsets frequency (imbalance) during infection leads to changed cytokine patterns. however, the effects of ev71 infection on t cell subsets were not clear. the objective of this study was to determine whether ev71-induced hfmd can be ex ...201424316007
a colorimetric-based accurate method for the determination of enterovirus 71 titer.the 50 % tissue culture infectious dose (tcid50) is still one of the most commonly used techniques for estimating virus titers. however, the traditional tcid50 assay is time consuming, susceptible to subjective errors and generates only quantal data. here, we describe a colorimetric-based approach for the titration of enterovirus 71 (ev71) using a modified method for making virus dilutions. in summary, the titration of ev71 using mtt or mts staining with a modified virus dilution method decrease ...201224293817
global impact of heparin on gene expression profiles in neural cells infected by enterovirus 71.heparan sulphate mimetics, particularly heparin (hep), have previously been shown to considerably inhibit infection of enterovirus 71 (ev71) in vero cells. therefore, in this study, a genome-wide dna microarray was performed to gain insight into the mechanism(s) of action of hep against infection of a human neural cell line, sk-n-sh, with a clinical strain of ev71.201424281657
how to understand the efficacy measurements for enterovirus type 71 vaccine?the choice of endpoint was most important for an efficacy vaccine trial. the objective of this paper is to gear toward answering questions about the rationality and scientificity of the primary endpoints choosing, case capturing and diagnosis strategy in our recently reported ev71 vaccine efficacy phase 3 trial. in order to obtain both high sensitivity and specificity in the case detecting, ev71-associated disease had been chosen as primary endpoint, a broad spectrum of clinical symptoms was sur ...201424280898
development and evaluation of a real-time method of simultaneous amplification and testing of enterovirus 71 incorporating a rna internal control system.human enterovirus 71 (ev71) is a primary etiological agent of hand, foot, and mouth disease (hfmd). the associated infections have posed a serious threat to the public health. in the present study, a real-time simultaneous amplification and testing (sat) technology was developed for detecting ev71 (sat-ev71). the rna of ev71 and an internal control (ic) were amplified and analyzed simultaneously by isothermal amplification and real-time detection of fluorescence using routine real-time pcr. furt ...201424269796
a 3c(pro)-dependent bioluminescence imaging assay for in vivo evaluation of anti-enterovirus 71 agents.enterovirus 71 (ev71), a member of picornaviridae, is one of the major pathogens of human hand, foot and mouth disease. ev71 mainly infects children and causes severe neurological complications and even death. the pathogenesis of ev71 infection is largely unknown, and no clinically approved vaccine or effective treatment is available to date. here we described a novel bioluminescence imaging approach for ev71 detection. in this approach, a plasmid-based reporter was constructed to express the fu ...201424263113
the cross-neutralizing activity of enterovirus 71 subgenotype c4 vaccines in healthy chinese infants and children.ev71 is one of major etiologic causes of hand-foot-mouth disease (hfmd) and leads to severe neurological complications in young children and infants. recently inactivated ev71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. however, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because rna recombination is seen more frequently in ev71 epidemics.201324260259
antiviral activity of guiqi polysaccharides against enterovirus 71 in vitro.in this study, we have investigated the antiviral activity of guiqi polysaccharides (gqp) upon enterovirus 71 (ev71) in vitro. an assay using methyl thiazolyl tetrazolium (mtt), and analyses of cytopathic effects (cpe) were used to examine the antiviral activity of gqp upon vero cells infected with ev71. the results revealed that gqp at concentrations below 31.2 μg/ml exhibited significant antiviral effects upon ev71 when applied under three different experimental protocols. gqp was most strongl ...201324254889
preclinical evaluation of the immunogenicity and safety of an inactivated enterovirus 71 candidate vaccine.human enterovirus 71 (ev71) is a significant cause of morbidity and mortality from hand, foot and mouth disease (hfmd) and neurological complications, particularly in young children in the asia-pacific region. there are no vaccines or antiviral therapies currently available for prevention or treatment of hfmd caused by ev71. therefore, the development of therapeutic and preventive strategies against hfmd is of growing importance. we report the immunogenic and safety profile of inactivated, purif ...201324244774
modification of picornavirus genomic rna using 'click' chemistry shows that unlinking of the vpg peptide is dispensable for translation and replication of the incoming viral rna.picornaviruses constitute a large group of viruses comprising medically and economically important pathogens such as poliovirus, coxsackievirus, rhinovirus, enterovirus 71 and foot-and-mouth disease virus. a unique characteristic of these viruses is the use of a viral peptide (vpg) as primer for viral rna synthesis. as a consequence, all newly formed viral rna molecules possess a covalently linked vpg peptide. it is known that vpg is enzymatically released from the incoming viral rna by a host p ...201424243841
clinico-radiological spectrum in enterovirus 71 infection involving the central nervous system in children.enterovirus 71 infection causes hand, foot and mouth disease in children, and can produce diverse neurologic complications. epidemics occurring in korea between 2009 and 2012 resulted in the death of some patients. the present study aimed to clarify the correlation between clinical features and mri findings in patients presenting with acute neurologic manifestations related to enterovirus 71 infection. based on their clinical features, the patients were classified into four clinical groups: (1) ...201424169271
structure of limp-2 provides functional insights with implications for sr-bi and cd36.members of the cd36 superfamily of scavenger receptor proteins are important regulators of lipid metabolism and innate immunity. they recognize normal and modified lipoproteins, as well as pathogen-associated molecular patterns. the family consists of three members: sr-bi (which delivers cholesterol to the liver and steroidogenic organs and is a co-receptor for hepatitis c virus), limp-2/lgp85 (which mediates lysosomal delivery of β-glucocerebrosidase and serves as a receptor for enterovirus 71 ...201324162852
a one-step dipstick assay for the on-site detection of nucleic acid.we have developed a one-step nucleic acid dipstick assay (nada) for visually detecting polymerase chain reaction (pcr) products within 3min. "one-step" means that there were no additional procedures between amplification and detection.201324161476
enterovirus 71 pathogenicity in monkeys and cotton rats.enterovirus 71 (ev71) is a neurovirulent non-polio enterovirus that can cause severe central nervous system (cns) infection in infants. vervet monkeys infected intracerebrally or intramuscularly with ev71 isolates from the bulgarian outbreak of 1975 developed clinical manifestations and pathological signs of encephalomyelitis and spinal poliomyelitis that were similar to ev71 neuroinfection in children. in addition, vervet monkeys with encephalomyelitis had severe alterations in the choroid plex ...201424158347
the population-based health effect of hand, foot and mouth disease in children in shanghai.an effective enterovirus 71 (ev71) vaccine is needed to control the annual outbreaks of hand, foot and mouth disease (hfmd) in china. adequate epidemiologic data relating to hfmd are needed to make decisions about appropriate public health interventions and implementation of the new ev71 vaccine.201424153009
impact of endothelial nitric oxide synthase gene polymorphism on severity of enterovirus 71-infection in chinese children.genetic polymorphism g894t on the endothelial nitric oxide synthase (enos) gene has been reported as a susceptibility factor in a number of diseases, but evidence of its effect on enterovirus 71 (ev71) infection is lacking. this study investigated the possible association between this polymorphism (rs1799983) and disease severity in chinese children with ev71 infection.201324140479
evaluation of the stability of enterovirus 71 virus-like particle.enterovirus 71 (ev71) is responsible for the outbreaks of hand-foot-and-mouth disease that caused significant mortality in children, but no vaccine is available yet. ev71 virus-like particle (vlp) is the empty capsid consisting of viral structural proteins but can elicit potent immune responses, rendering vlp a promising ev71 vaccine candidate. to evaluate whether vlp remains stable after long-term storage, which is crucial for advancing the vlp vaccine to the clinical setting, we evaluated the ...201424140131
frequency of human enterovirus 71 in children under 8 years old with aseptic menengitis in tehran.human enterovirus 71 (hev71) was isolated for the first time from an infant with encephalitis in california in 1969 and then spread through the world. it has emerged as a major cause of a vast variety of diseases such as epidemics of hand, foot and mouth disease (hfmd), aseptic meningitis (am), acute flaccid paralysis, and encephalitis. the aim of this study was to determine the prevalence of enterovirus 71 in children < 8 years old who were hospitalized due to primary diagnosis of am in tehran.201324133924
chimeric virus-like particle vaccines displaying conserved enterovirus 71 epitopes elicit protective neutralizing antibodies in mice through divergent mechanisms.enterovirus 71 (ev71) is a major causative agent of hand, food, and mouth disease, which frequently occurs in young children. since there are 11 subgenotypes (a, b1 to b5, and c1 to c5) within ev71, an ev71 vaccine capable of protecting against all of these subgenotypes is desirable. we report here the vaccine potential and protective mechanism of two chimeric virus-like particles (vlps) presenting conserved neutralizing epitopes of ev71. we show that fusions of hepatitis b core antigen (hbc) wi ...201424131712
epidemiology of enterovirus 71 infections in taiwan.enterovirus 71 (ev71) was first described in usa in 1969 but retrospective studies in the netherlands further detected ev71 in the clinical specimens collected in 1963. ev71 has one single serotype measured by using hyperimmune animal antisera but can be phylogenetically classified into three genogroups (a, b, and c) including 11 genotypes (a, b1-b5, c1-c5). in taiwan, ev71 caused a large-scale nationwide epidemic in 1998. retrospective studies further detected ev71 in clinical specimens collect ...201424120535
the enteroviruses: problems in need of treatments.specific antiviral therapy is currently not available for enterovirus (ev) infections. poliomyelitis, ev 71 neurologic disease, and neonatal ev disease are three manifestations of ev infections that exemplify the importance of developing antivirals for ev infections. despite tremendous strides in the effort to eradicate polio through vaccination, challenges remain, including the potential for transmission of neurovirulent vaccine-derived polioviruses which have genetically reverted from live-att ...201424119825
human enterovirus 71 epidemics: what's next?human enterovirus 71 (ev71) epidemics have affected various countries in the past 40 years. ev71 commonly causes hand, foot and mouth disease (hfmd) in children, but can result in neurological and cardiorespiratory complications in severe cases. genotypic changes of ev71 have been observed in different places over time, with the emergence of novel genotypes or subgenotypes giving rise to serious outbreaks. since the late 1990s, intra- and inter-typic recombination events in ev71 have been increa ...201324119538
immunogenicity, safety, and lot consistency of a novel inactivated enterovirus 71 vaccine in chinese children aged 6 to 59 months.the determination of lot-to-lot consistency in the manufacturing process is a mandatory step in the clinical development of the novel enterovirus 71 (ev71) vaccine. a phase iii, randomized, placebo-controlled, double-blind trial assessed the lot consistency, immunogenicity, and safety of the ev71 vaccine in children aged 6 to 59 months. healthy children (n = 1,400) received one of three lots of the ev71 vaccine containing 400 u of ev71 antigen or a placebo at days 0 and 28. blood samples were co ...201324108780
chlorogenic acid inhibits the replication and viability of enterovirus 71 in vitro.enterovirus 71 (ev71) is an etiology for a number of diseases in humans. traditional chinese herbs have been reported to be effective for treating ev71 infection. however, there is no report about the antiviral effects of cha against ev71. in this study, plaque reduction assay demonstrated that the inhibitory concentration 50% (ic50) of cha on ev71 replication is 6.3 µg/ml. when both cha (20 µg/ml) and ev71 were added, or added post-infection at different time points, cha was able to effectively ...201324098754
association of functional polymorphisms in the mxa gene with susceptibility to enterovirus 71 infection.myxovirus resistance a (mxa) is an antiviral protein induced by type i interferons α and β (ifn-α and ifn-β) that can inhibit virus replication. we examined whether the mxa polymorphisms were related to the risk and severity of enterovirus 71 (ev71) infection in chinese populations. the mxa c-123a and g-88t polymorphisms were genotyped in two independent case-control populations in china by polymerase chain reaction-based restriction fragment length polymorphism (pcr-rflp) analysis. multivariate ...201424085612
bedside immunochromatographic test for enterovirus 71 infection in children.enterovirus 71 (ev71) causes frequent outbreaks worldwide, particularly in the asia-pacific area. its quick spread is a critical challenge for public health and timely preventive measures and clinical management therefore rely on early detection. there is a need for a rapid, easy-to-use, and reliable method for detecting ev71 infections.201324084600
is a monovalent vaccine against enterovirus 71 sufficient? a review of enterovirus 71 vaccine development based on enterovirus surveillance in taiwan. 201324079713
enterovirus 71 vp1 activates calmodulin-dependent protein kinase ii and results in the rearrangement of vimentin in human astrocyte cells.enterovirus 71 (ev71) is one of the main causative agents of foot, hand and mouth disease. its infection usually causes severe central nervous system diseases and complications in infected infants and young children. in the present study, we demonstrated that ev71 infection caused the rearrangement of vimentin in human astrocytoma cells. the rearranged vimentin, together with various ev71 components, formed aggresomes-like structures in the perinuclear region. electron microscopy and viral rna l ...201324073199
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