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anti-enterovirus 71 effects of chrysin and its phosphate ester.enterovirus 71 (ev71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. the anti-ev71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. by using the predicting program autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3cpro activity. replication of viral rna and production of viral capsid protein and the infect ...201424598537
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
new coxsackievirus b4 genotype circulating in inner mongolia autonomous region, china.hand, foot, and mouth disease (hfmd) surveillance was initiated in the inner mongolia autonomous region of china in 2007, a crucial scrutiny for monitoring the prevalence of enterovirus serotypes associated with hfmd patients. however, this surveillance mostly focused on enterovirus 71 (ev-a71) and coxsackievirus a16; therefore, information on other enterovirus serotypes is limited. to identify the other circulating enterovirus serotypes in the hfmd outbreaks in inner mongolia in 2010, clinical ...201424595311
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
enterovirus infection in children attending two outpatient clinics in zhejiang province, china.enteroviruses are responsible for hand, foot, and mouth disease, and have caused many deaths in china during recent years. but the natural history of enterovirus infection in children, especially asymptomatic children, is not yet clear. from april 2011 to may 2012, 505 stool and throat swab samples of children attending outpatients clinics in two hospitals were collected weekly to test for enterovirus 71, coxsackievirus a16, and other enterovirus nucleic acids by real-time rt-pcr. two hundred si ...201424519430
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
[hand, foot and mouth disease--more than a harmless "childhood disease"].hand, foot and mouth disease (hfmd) is a highly contagious, world-wide distributed viral illness that affects predominantly children. it is caused by several enteroviruses, such as coxsackieviruses a6, a10, a16 and enterovirus 71. in most cases, hfmd follows a benign and self-limiting course. after an incubation period of 3 to 10 days, fever and sore throat, the first symptoms of the disease, appear. a few days later, maculopapular or vesicular eruptions form on the palms and soles as well as in ...201424490433
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
dermatological spectrum of hand, foot and mouth disease from classical to generalized exanthema.hand, foot and mouth disease (hfmd) is classically defined as a childhood fever accompanied by a rash with vesicles or erosions of the oral mucosa, hands, feet and sometimes the buttocks. severe neurological complications are associated with enterovirus 71 outbreaks in asia. recently, it has been suggested that hfmd is related to coxsackie virus a6 (cv-a6) when there is an atypical rash. the objective of the study is to determine the dermatological pattern of hfmd and to identify the virus serot ...201424463804
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
hand, foot and mouth disease in guangdong, china, in 2013: new trends in the continuing epidemic.millions of incidents of hand, foot and mouth disease occur annually in china, with eva71 and cva16 as two major causative pathogens. a provincial surveillance system has been implemented in guangdong for almost 5 years to analyze the aetiological spectrum and epidemic changes. an unusual enterovirus type, cva6, was identified as the predominant serotype associated with an hfmd epidemic from late 2012 to 2013. in contrast to virus strains isolated before, all cva6/chn/2012-2013 strains segregate ...201424428125
development of loop-mediated isothermal amplification (lamp) for universal detection of enteroviruses.enteroviruses are found in most environments and cause several diseases in humans. loop-mediated isothermal amplification (lamp) was adapted and evaluated for the rapid detection of enteroviruses. based on the highly conserved 5' untranslated region (5'-utr) of the human enteroviruses (hevs), particularly human enterovirus a (hev-a) and hev-b, a set of universal primers was designed. the lamp amplification was carried out under isothermal conditions at 61 °c, depending on the template concentrat ...201424426171
recombination strategies and evolutionary dynamics of the human enterovirus a global gene pool.we analysed natural recombination in 79 human enterovirus a strains representing 13 serotypes by sequencing of vp1, 2c and 3d genome regions. the half-life of a non-recombinant tree node in coxsackieviruses 2, 4 and 10 was only 3.5 years, and never more than 9 years. all coxsackieviruses that differed by more than 7 % of the nucleotide sequence in any genome region were recombinants relative to each other. enterovirus 71 (ev71), on the contrary, displayed remarkable genetic stability. three majo ...201424425417
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
[observation on virus shedding periods of enterovirus-71 and coxsackievirus a 16 monitored by nucleic acids determination in stool samples of children with hand, foot and mouth disease].to observe the duration of enterovirus-71 (ev71) and coxsackievirus a 16 (coxa16) viral shedding in stool samples of children with hand, foot and mouth disease (hfmd) infected with ev71 and coxa16 and to explore the relationship between the duration of intestinal virus shedding and the severity of illness of children with hfmd.201324406235
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
prevalence of multiple enteroviruses associated with hand, foot, and mouth disease in shijiazhuang city, hebei province, china: outbreaks of coxsackieviruses a10 and b3.hand, foot, and mouth disease (hfmd) has been one of the most common infectious diseases in shijiazhuang city, as is the situation in china overall. in the national hfmd surveillance system, the pathogen detection was focused on ev-a71 and cva16, and therefore, information on the other evs is very limited. in order to identify the circulating ev serotypes in the hfmd outbreaks in shijiazhuang city during 2010-2012, 4045 patients presented with hfmd were recruited in the study, and clinical sampl ...201424392117
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
enterovirus 2apro targets mda5 and mavs in infected cells.rig-i-like receptors (rlrs) mda5 and rig-i are key players in the innate antiviral response. upon recognition of viral rna, they interact with mavs, eventually inducing type i interferon production. the interferon induction pathway is commonly targeted by viruses. how enteroviruses suppress interferon production is incompletely understood. mda5 has been suggested to undergo caspase- and proteasome-mediated degradation during poliovirus infection. additionally, mavs is reported to be cleaved duri ...201424390337
tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in ev71 encephalomyelitis.enterovirus 71 (ev71; family picornaviridae, species human enterovirus a) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. we investigated extra-central nervous system (extra-cns) tissues capable of supporting ev71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor b2 (scarb2), and p-selectin glycoprotein ligand-1 (psgl-1). formalin-fixed, paraffin-embedded ...201424378407
[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
human enterovirus 71 uncoating captured at atomic resolution.human enterovirus 71 (ev71) is the major causative agent of severe hand-foot-and-mouth diseases (hfmd) in young children, and structural characterization of ev71 during its life cycle can aid in the development of therapeutics against hfmd. here, we present the atomic structures of the full virion and an uncoating intermediate of a clinical ev71 c4 strain to illustrate the structural changes in the full virion that lead to the formation of the uncoating intermediate prepared for rna release. alt ...201424352461
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
combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change.fitting of atomic components into electron cryo-microscopy (cryoem) density maps is routinely used to understand the structure and function of macromolecular machines. many fitting methods have been developed, but a standard protocol for successful fitting and assessment of fitted models has yet to be agreed upon among the experts in the field. here, we created and tested a protocol that highlights important issues related to homology modelling, density map segmentation, rigid and flexible fitti ...201424333899
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
monoclonal antibodies for diagnosis of enterovirus 71.enterovirus 71 (ev71), one of the major causative agents of hand, foot, and mouth disease (hfmd), is now recognized as an emerging neurotropic virus in asia and may cause severe neurologic complications and mortalities. laboratory diagnosis of ev71 infection must be efficient and accurate, which could be accomplished by various immunoassays. in this study we use a live ev71 isolate, tainan/4643/98, with genotype c2 as an immunogen to sensitize balb/c (h-2(d)) mice and then generate the ev71-spec ...201324328741
seroprevalence of human enterovirus 71 and coxsackievirus a16 in guangdong, china, in pre- and post-2010 hfmd epidemic period.human enterovirus 71 and coxsackie a16 have caused many outbreaks in the last decade in mainland china, resulting in thousands of fatal cases. seroepidemiology which provides important information to document population immunity is rare in china.201324324604
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
formalin-inactivated ev71 vaccine candidate induced cross-neutralizing antibody against subgenotypes b1, b4, b5 and c4a in adult volunteers.enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia. no effective ev71 vaccine is available. a randomized and open-label phase i clinical study registered with clinicaltrials.gov #nct01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated ev71 vaccine candidate (ev71vac) at 5- and 10-µg doses. in this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotype ...201324278177
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
coxsackievirus a16: epidemiology, diagnosis, and vaccine.coxsackievirus 16 (ca16) is one of the major pathogens associated with hand, foot, and mouth disease (hfmd) in infants and young children. in recent years, ca16 and human enterovirus 71 (ev71) have often circulated alternatively or together in the western pacific region, which has become an important public health problem in this region. hfmd caused by ca16 infection is generally thought to be mild and self-limiting. however, recently several severe and fatal cases involving ca16 have been repor ...201424231751
epidemiology and clinical characteristics of hand foot, and mouth disease in a shenzhen sentinel hospital from 2009 to 2011.we investigated the epidemiological and clinical data of all hand, foot, and mouth disease (hfmd) cases in a sentinel hospital of shenzhen, china from 2009 to 2011.201324225231
coxsackievirus a6-induced hand-foot-mouth disease.hand-foot-mouth disease (hfmd) is an acute, self-limited, highly contagious viral illness that commonly affects children younger than 5 years. it is most typically caused by enterovirus 71 or coxsackievirus a16 and results in asymptomatic infection or mild disease. immunocompetent adults are rarely affected. recently, there have been increasing reports of a more severe form of hfmd associated with fevers, joint pains, and widespread painful eruptions. some of these patients required hospitalizat ...201324172861
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
enterovirus genotypes causing hand foot and mouth disease in shanghai, china: a molecular epidemiological analysis.a rapid expansion of hand, foot, and mouth disease (hfmd) outbreaks has occurred and caused deaths in china in recent years, but little is known about the other etiologic agents except enterovirus 71 (ev71) and coxsackievirus a 16 (ca16). the objective of this study is to determine the genotype compositions of enterovirus causing hfmd in shanghai and identify any associations between enterovirus types and clinical manifestations.201324148902
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
heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy.although several factors participating in enterovirus 71 (ev71) entry and replication had been reported, the precise mechanisms associated with these events are far from clear. in the present study, we showed that heat shock protein 90 (hsp90) is a key element associated with ev71 entry and replication in a human rhabdomyosarcoma of rd cells. inhibition of hsp90 by pretreating host cells with hsp90β sirna or blocking hsp90 with a hsp90-specific antibody or geldanamycin (ga), a specific inhibitor ...201324098578
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
eupafolin and ethyl acetate fraction of kalanchoe gracilis stem extract show potent antiviral activities against enterovirus 71 and coxsackievirus a16.enterovirus 71 (ev71) and coxsackievirus a16 (coxa16) are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. kalanchoe gracilis, da-huan-hun, is a chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. our prior report (2012) cited k. gracilis leaf extract as moderately active against ev71 and coxa16. this study further rates antienteroviral potent ...201324078828
enterovirus 71 vp1 activates calmodulin-dependent protein kinase ii and results in the rearrangement of vimentin in human astrocyte cells.enterovirus 71 (ev71) is one of the main causative agents of foot, hand and mouth disease. its infection usually causes severe central nervous system diseases and complications in infected infants and young children. in the present study, we demonstrated that ev71 infection caused the rearrangement of vimentin in human astrocytoma cells. the rearranged vimentin, together with various ev71 components, formed aggresomes-like structures in the perinuclear region. electron microscopy and viral rna l ...201324073199
environmental alkylphenols modulate cytokine expression in plasmacytoid dendritic cells.alkylphenols, such as nonylphenol (np) and 4-octylphenol (4-op), have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. plasmacytoid dendritic cells (pdcs) can secrete large amounts of type i ifns and are critical in immune regulation. however, there has been limited study about the influence of alkylphenols on the function of pdcs.201324039973
atypical hand-foot-and-mouth disease associated with coxsackievirus a6 infection.hand-foot-and-mouth disease (hfmd) is an acute viral illness commonly caused by coxsackievirus (cv)-a16 and enterovirus 71 infections. recently, atypical hfmd has been reported in association with cv-a6, an uncommon enterovirus strain.201324035209
[relationship between g6pd deficiency and hand-foot-mouth disease induced by enterovirus 71].to study the influence of glucose-6-phosphate dehydrogenase (g6pd) deficiency on hand-foot-mouth disease (hfmd) induced by enterovirus 71 (ev71) , and possible mechanisms.201324034918
molecular epidemiology of enterovirus 71, coxsackievirus a16 and a6 associated with hand, foot and mouth disease in spain.hand, foot and mouth disease (hfmd) is a childhood illness frequently caused by genotypes belonging to the enterovirus a species, including coxsackievirus (cv)-a16 and enterovirus (ev)-71. between 2010 and 2012, several outbreaks and sporadic cases of hfmd occurred in different regions of spain. the objective of the present study was to describe the enterovirus epidemiology associated with hfmd in the country. a total of 80 patients with hfmd or atypical rash were included. detection and typing ...201424033818
[cloning, expression and activity determination of capsid protein vp1 of enterovirus type 71]. 201324027809
human astrocytic cells support persistent coxsackievirus b3 infection.enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. here, we investigated the susceptibility of three human brain cell lines, ccf-sttg1, t98g, and sk-n-sh, to infection with three enterovirus serotypes: coxsackievirus b3 (cvb3), enterovirus 71, and coxsackievirus a9. persistent inf ...201324027313
an open conformation determined by a structural switch for 2a protease from coxsackievirus a16.coxsackievirus a16 belongs to the family picornaviridae, and is a major agent of hand-foot-and-mouth disease that infects mostly children, and to date no vaccines or antiviral therapies are available. 2a protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4g. here we present the crystal structure of coxsackievirus a16 2a protease, which interestingly forms hexamers in crystal as well a ...201324026848
coxsackievirus a6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review.hand, foot and mouth disease (hfmd) is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands and feet and in the oral cavity. it affects predominantly children and/or immunocompromised adults. it usually follows a benign and self-limiting course. however, hfmd cases with severe or lethal complications such as encephalitis, meningitis, pulmonary edema and myocarditis have also been reported, mostly in children, but also in adults. high infe ...201324019771
crystal structure of 2a proteinase from hand, foot and mouth disease virus.ev71 is responsible for several epidemics worldwide; however, the effective antiviral drug is unavailable to date. the 2a proteinase (2a(pro)) of ev71 presents a promising drug target due to its multiple roles in virus replication, inhibition of host protein synthesis and evasion of innate immunity. we determined the crystal structure of ev71 2a(pro) at 1.85å resolution, revealing that the proteinase maintains a chymotrypsin-like fold. the active site is composed of the catalytic triads c110a, h ...201323973886
proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71.to clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (hfmd) infected by enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe hfmd children and 5 healthy children.201323961958
transgenic mouse model for the study of enterovirus 71 neuropathogenesis.enterovirus 71 (ev71) typically causes mild hand-foot-and-mouth disease in children, but it can also cause severe neurological disease. recently, epidemic outbreaks of ev71 with significant mortality have been reported in the asia-pacific region, and ev71 infection has become a serious public health concern worldwide. however, there is little information available concerning ev71 neuropathogenesis, and no vaccines or anti-ev71 drugs have been developed. previous studies of this disease have used ...201323959904
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