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unusual skin manifestation of hand, foot and mouth disease associated with coxsackievirus a6: cases report.hand, food, and mouth disease (hfmd) is a highly contagious disease caused by enteroviruses infection. it is a health problem in young children under 5 years of age worldwide. the common causative agents are coxsackievirus a 16 (ca16) and enterovirus 71 (ev71). in recent years, coxsackievirus a6 (ca6) has emerged to be one of the major etiologic agents of hfmd worldwide including in thailand.201526203408
combination of intratypic and intertypic recombinant events in ev71: a novel evidence for the "triple-recombinant" strains of genotype a viruses in mainland china from 2008 to 2010.the first enterovirus 71 (ev71) strain isolated in 1969 was classified as genotype a. it is interesting that the genotype a disappeared nearly 40 years until its re-emergence in mainland china in 2008-2010. few studies on genetic characterization of the re-emerged genotype a viruses have been reported. in this study, a series of analyses were performed on molecular epidemiology and genome recombination of genotype a viruses in china. phylogenetic analysis indicated that except for 17 reported ge ...201525724176
[analysis of seroepidemiology of enterovirus 71 diseases in children in jiangsu province].to analyze the dynamic pattern and the distributive characteristics of neutralizing antibody against enterovirus 71 (ev-a71 ) in children aged 6-35 months in jiangsu province from 2012 to 2014.201526887297
impact of human enterovirus 71 genotypes in meningoencephalitis in iran.since the importance of poliovirus has diminished, as a result of its elimination in the majority of countries, non-polioviruses are emerging as causative agents of severe central nervous system (cns) involvement. outbreaks of enterovirus 71 (ev71)-associated cns infections have recently been reported in asia, australia, and europe.201526865943
analysis on the sequence of the whole genome of an isolated enterovirus 71 strain.an enterovirus 71 (ev71) strain query was isolated from a patient specimen in 2015. in order to known about its genetic evolution, this study amplified gene fragment of the isolated stain by rt-pct and carried out sequencing of the total genome. the homology and genetic evolution of the gene sequence of the virus strain in the study were analyzed. the results showed that the isolated ev71 strain in this study had higher homology of nucleotide sequence and amino acid sequence with other virus str ...201526884986
[inactivation of ev71 by exposure to heat and ultraviolet light].enterovirus 71 (ev71) is a major agent of hand, foot and mouth disease that can cause a severe burden of disease to children. to identify an effective method for the control and prevention of ev71, we studied the effect of exposure to heat and ultraviolet (uv) light upon ev71 inactivation. we found that exposure to 50 degrees c could not inactivate the infectivity of ev71. however, exposure to 60 degrees c and 70 degrees c could inactivate ev71 effectively. ev71 could be inactivated after exposu ...201526738287
antiviral effects of reduning injection against enterovirus 71 and possible mechanisms of action.the present study was designed to evaluate the protective effects of reduning injection against enterovirus 71 (ev71) in vero cells and in mice. the vero cells were infected with 100 and 50 tcid50 (50% tissue culture infective dose) of ev71, respectively. the inhibition of reduning injection on cytopathic effect (cpe) was detected. meanwhile, a mouse model produced by intraperitoneal ev71-infection (10(6) tcid50), was used to investigate the protective effects of reduning injection. the total su ...201526721706
glucose-6-phosphate dehydrogenase enhances antiviral response through downregulation of nadph sensor hscarg and upregulation of nf-κb signaling.glucose-6-phosphate dehydrogenase (g6pd)-deficient cells are highly susceptible to viral infection. this study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes-tumor necrosis factor alpha (tnf-α) and gtpase myxovirus resistance 1 (mx1)-in g6pd-knockdown cells upon human coronavirus 229e (hcov-229e) and enterovirus 71 (ev71) infection. molecular analysis revealed that the promoter activities of tnf-α and mx1 were downregulated in g6pd-knockdown cell ...201526694452
a functional polymorphism in ifnar1 gene is associated with susceptibility and severity of hfmd with ev71 infection.enterovirus 71 (ev71), one of the major pathogens of hand, foot and mouth disease (hfmd), results in millions of infections and hundreds of deaths each year in southeast asia. biased infection and variable clinical manifestations of ev71 hfmd indicated that host genetic background played an important role in the occurrence and development of the disease. we identified the mrna profiles of ev71 hfmd patients, which type i interferon (ifn) pathway related genes were down-regulated. four single nuc ...201526679744
recent progress towards novel ev71 anti-therapeutics and vaccines.enterovirus 71 (ev71) is a group of viruses that belongs to the picornaviridae family, which also includes viruses such as polioviruses. ev71, together with coxsackieviruses, is widely known for its association with hand foot mouth disease (hfmd), which generally affects children age five and below. besides hfmd, ev71 can also trigger more severe and life-threatening neurological conditions such as encephalitis. considering the lack of a vaccine and antiviral drug against ev71, together with the ...201526670245
studies on inhibition of proliferation of enterovirus-71 by compound yz-ly-0.in recent years, hand-foot-and-mouth disease (hfmd), which is caused by enteroviruses, has emerged as a serious illness. it affects mainly children under the age of five and results in high fatality rates. enterovirus 71 (ev71) is the main causative agent of hfmd in china and currently there are no effective anti-viral drugs available to treat hfmd. in the present study, we screened compounds for inhibition of proliferation of ev71. compound yz-ly-0 stalled the life cycle of ev71. the inhibitor ...201526640412
relationship between serologic response and clinical symptoms in children with enterovirus 71-infected hand-foot-mouth disease.this study aimed to explore the correlation between clinical symptoms, including rash and fever, and serum antibody reaction to enterovirus 71 (ev71) infection in children hospitalized due to hand-foot-mouth disease (hfmd). from may 2014 to july 2014, a total of 547 children hospitalized due to hfmd in children's hospital of fudan university were enrolled retrospectively. rna levels of ev71 and ca16 in fecal, serum, and cerebrospinal fluid specimens were measured using quantitative real-time rt- ...201526617898
[inosine pranobex - cytotoxic activities and effect of on replication of human parainfluenza viruses (hpiv-2, hpiv-4), entroviruses (ca16, ev71) and adenoviruses (hadv-2, hadv-5) in vitro].there are no specific antivirals designed for many viral infections. inosine pranobex (pi) is a purine nucleoside that is involved in a wide variety of intracellular biochemical processes. the mechanism of action in human body is still unclear but numerous studies have demonstrated that this drug inhibits viral replication and exhibit pleiotropic effect. we evaluated in vitro effect of inosine pranobex (pi) on replication of human viruses: parainfluenza viruses (hpiv-2, hpiv-4), entroviruses a ( ...201526591662
engineering enhanced vaccine cell lines to eradicate vaccine-preventable diseases: the polio end game.vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. to enhance vaccine production at reduced costs, a genome-wide rna interference (rnai) screen was performed to identify gene knockdown events that enhanced poliovirus replication. primary screen hits were validated in a vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. multiple single and dual gene silencing events i ...201526581994
host microrna mir-197 plays a negative regulatory role in the enterovirus 71 infectious cycle by targeting the ran protein.enterovirus 71 (ev71), a member of picornaviridae, is associated with severe central nervous system complications. in this study, we identified a cellular microrna (mirna), mir-197, whose expression was downregulated by viral infection in a time-dependent manner. in mir-197 mimic-transfected cells, ev71 replication was inhibited, whereas the internal ribosome entry site (ires) activity was decreased in ev71 strains with or without predicted mir-197 target sites, indicating that mir-197 targets h ...201526581983
cyanohydrin as an anchoring group for potent and selective inhibitors of enterovirus 71 3c protease.cyanohydrin derivatives as enterovirus 71 (ev71) 3c protease (3c(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. compared with the reported inhibitors, cyanohydrins (1s,2s,2's,5s)-16 and (1r,2s,2's,5s)-16 exhibited significantly improved activity and attractive selectivity profiles against other proteases, which were a result of the specific interactions between the cyanohydrin moiety and the catalytic site of 3c(pro). cyanohydrin as an anchorin ...201526571192
transmission patterns of human enterovirus 71 to, from and among european countries, 2003 to 2013.enterovirus 71 (ev-71) is involved in epidemics of hand, foot, and mouth disease (hfmd) and has been reported to occur with severe neurological complications in eastern and south-east asia. in other geographical areas, the transmission of this virus is poorly understood. we used large sequence datasets (of the gene encoding the viral protein 1, vp1) and a bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of ev-71 subgenogroups b4, b5, c1, c2, a ...201526530407
pros and cons of vp1-specific maternal igg for the protection of enterovirus 71 infection.enterovirus 71 (ev71) causes hand, foot, and mouth diseases and can result in severe neurological disorders when it infects the central nervous system. thus, there is a need for the development of effective vaccines against ev71 infection. here we report that viral capsid protein 1 (vp1), one of the main capsid proteins of ev71, efficiently elicited vp1-specific immunoglobulin g (igg) in the serum of mice immunized with recombinant vp1. the vp1-specific igg produced in female mice was efficientl ...201526529069
[progress in research on structure, function and antiviral of enterovirus a71 3c protein].enterovirus a71 (ev-a71) causes hand, foot, and mouth disease (hfmd) and various neurological complications, including aseptic meningitis and neurogenic pulmonary edema in young children. hfmd caused by ev-a71 have broken out several times in the asia-pacific region since 2007. and it has been a serious threat to public health. there is no effective vaccine or antiviral drug. the pathogenesis of ev-a71 infection is unknown, and ev-a71 3c protein plays an irreplaceable role in replication and ant ...201526524922
risk factors for severe hand foot mouth disease in singapore: a case control study.hand foot mouth disease (hfmd) is a common childhood infection that can potentially lead to serious complications. the aim of this study is to identify risk factors of acquiring severe hfmd in our population.201526520791
enterovirus 71 induces autophagy by regulating has-mir-30a expression to promote viral replication.enterovirus 71 (ev71), the etiological agent of hand-foot-and-mouth disease, has increasingly become a public health challenge around the world. previous studies reported that ev71 infection can induce autophagic machinery to enhance viral replication in vitro and in vivo, but did not address the underlying mechanisms. increasing evidence suggests that autophagy, in a virus-specific manner, may function to degrade viruses or facilitate viral replication. in this study, we reported that ev71 infe ...201526515789
identification of positively charged residues in enterovirus 71 capsid protein vp1 essential for production of infectious particles.enterovirus 71 (ev71), a positive-stranded rna virus, is the major cause of hand, foot, and mouth disease (hfmd) in children, which can cause severe central nervous system disease and death. the capsids of ev71 consist of 60 copies of each of four viral structural proteins (vp1 to vp4), with vp1, vp2, and vp3 exposed on the surface and vp4 arranged internally. vp1 plays a central role in particle assembly and cell entry. to gain insight into the role of positively charged residues in vp1 functio ...201526512078
identification, synthesis and pharmacological evaluation of novel anti-ev71 agents via cyclophilin a inhibition.in this work, the relationship between cyclophilin a (cypa) and ev71 prompted us to screen a series of small molecular cypa inhibitors which were previously reported by our group. among them, compounds 1 and 2 were discovered as non-immunosuppressive anti-ev71 agents with an ec50 values of 1.07±0.17μm and 3.36±0.45μm in virus assay, respectively, which were desirably for the further study. the subsequent chemical modifications derived a novel class of molecules, among which compound 11 demonstra ...201526564266
antiviral activities of several oral traditional chinese medicines against influenza viruses.influenza is still a serious threat to human health with significant morbidity and mortality. the emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. traditional chinese medicines (tcms) may be an alternative to overcome the challenge. here, 10 oral proprietary chinese medicines were selected to evaluate their anti-influenza activities. these drugs exhibit potent inhibitory effects against influenza a h1n1, influenza a h3n2, and influenza b virus. i ...201526557857
[expression and significance of toll-like receptors 7 and 8 in brain and lung tissues of death cases caused by ev71 infection].to study the significance of toll-like receptors (tlr) -7 and -8 in the pathogenesis of infection caused by enterovirus type 71 (ev71) through measuring the expression of tlr7 and tlr8 in brain and lung tissues from the death cases caused by ev71 infection.201526483222
comparing the primary and recall immune response induced by a new ev71 vaccine using systems biology approaches.three inactivated ev71 whole-virus vaccines have completed phase iii clinical trials in mainland china, with high efficacy, satisfactory safety, and sustained immunogenicity. however, the molecular mechanisms how this new vaccine elicit potent immune response remain poorly understood. to characterize the primary and recall responses to ev71 vaccines, pbmc from 19 recipients before and after vaccination with ev71 vaccine are collected and their gene expression signatures after stimulation with ev ...201526465882
intestinal detoxification time of hand-foot-and-mouth disease in children with ev71 infection and the related factors.hand-foot-and-mouth disease (hfmd) is a common pediatric infectious disease caused by a variety of intestinal viruses. enterovirus 71 (ev71) is the primary pathogen that might cause severe symptoms and even death in children with hfmd. this study aimed to investigate the intestinal detoxification time of hfmd children with ev71 infection and its related factors.201526454441
systematic review of economic evaluations of vaccination programs in mainland china: are they sufficient to inform decision making?the purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland china. we searched for economic evaluations of vaccination in china published prior to august 3, 2015 in eight english-language and three chinese-language databases. each article was appraised against the 19-item consensus on health economic criteria list (chec-list). we found 23 papers evaluating vaccines against hepatitis b (8 articles), streptococcus pneumoniae (5 articles), hu ...201526435189
the suramin derivative nf449 interacts with the 5-fold vertex of the enterovirus a71 capsid to prevent virus attachment to psgl-1 and heparan sulfate.nf449, a sulfated compound derived from the antiparasitic drug suramin, was previously reported to inhibit infection by enterovirus a71 (ev-a71). in the current work, we found that nf449 inhibits virus attachment to target cells, and specifically blocks virus interaction with two identified receptors--the p-selectin ligand, psgl-1, and heparan sulfate glycosaminoglycan--with no effect on virus binding to a third receptor, the scavenger receptor scarb2. we also examined a number of commercially a ...201526430888
a bivalent virus-like particle based vaccine induces a balanced antibody response against both enterovirus 71 and norovirus in mice.noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. genogroup ii.4 (gii.4) strains are responsible for the majority of norovirus outbreaks. enterovirus 71 (ev71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in asia-pacific regions, resulting in significant morbidity and mortality in young children. however, no vaccine is commercially availab ...201526424606
similar protective immunity induced by an inactivated enterovirus 71 (ev71) vaccine in neonatal rhesus macaques and children.during the development of enterovirus 71 (ev71) inactivated vaccine for preventing human hand, foot and mouth diseases (hfmd) by ev71 infection, an effective animal model is presumed to be significant and necessary. our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of hfmd, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during ev71 infection. althou ...201526419198
antibodies to p-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.p-selectin glycoprotein ligand-1 (psgl-1) has been proved to serve as the functional receptor for enterovirus 71 (ev71). we found the abundant expression of psgl-1 on monocyte-derived dendritic cells (mddcs). however, we have previously demonstrated that mddcs did not support efficient replication of ev71. dendritic cells (dcs) have been described to be subverted by various viruses including ev71 for viral dissemination, we thus explore the potential contribution of psgl-1 on dc-mediated ev71 tr ...201526399965
enterovirus 71 infection caused neuronal cell death and cytokine expression in cultured rat neural cells.fatal enterovirus type-71 (ev71) cases are associated with central nervous system infection characterized by inflammatory cell infiltration and activation, cytokine overproduction, and neuronal cell death. although ev71 antigen has been detected in neurons and glia, the molecular mechanisms underlying ev71-associated neuroinflammation and neuronal cell death are not fully understood. using cultured rodent neural cell models, we found that ev71 infection preferentially caused cell death in neuron ...201526399559
enterovirus 71 2c protein inhibits nf-κb activation by binding to rela(p65).viruses evolve multiple ways to interfere with nf-κb signaling, a key regulator of innate and adaptive immunity. enterovirus 71 (ev71) is one of primary pathogens that cause hand-foot-mouth disease. here, we identify rela(p65) as a novel binding partner for ev71 2c protein from yeast two-hybrid screen. by interaction with ipt domain of p65, 2c reduces the formation of heterodimer p65/p50, the predominant form of nf-κb. we also show that picornavirus 2c family proteins inhibit nf-κb activation an ...201526394554
immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy chinese children: a report of further observations.to investigate the long-term effects on immunity of an inactivated enterovirus 71 (ev71) vaccine and its protective efficacy.201526381232
anti-enterovirus 71 agents of natural products.this review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. it covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. in total, 58 naturally-occurring anti-ev71 compounds are recorded.201526370955
seroprevalence of enterovirus 71 antibody among children in china: a systematic review and meta-analysis.hand, foot and mouth disease mostly affects children and carries a substantial disease burden in the western pacific region. enterovirus 71 (ev71) is the most virulent causative agent, and a monovalent vaccine against ev71 will soon become commercially available in china. an improved understanding of ev71 epidemiology would aid policy decisions regarding childhood immunization in china. we aimed to assess and summarize information to date from individual seroepidemiologic studies of ev71 in main ...201526368058
tia-1 and tiar interact with 5'-utr of enterovirus 71 genome and facilitate viral replication.enterovirus 71 is one of the major causative pathogens of hfmd in children. upon infection, the viral rna is translated in an ires-dependent manner and requires several host factors for effective replication. here, we found that t-cell-restricted intracellular antigen 1 (tia-1), and tia-1 related protein (tiar) were translocated from nucleus to cytoplasm after ev71 infection and localized to the sites of viral replication. we found that tia-1 and tiar can facilitate ev71 replication by enhancing ...201526363455
development of a specific latex agglutination test to detect antibodies of enterovirus 71.a latex agglutination test (lat) was developed for the rapid detection of antibodies against the vp1 or vp1 proteins of enterovirus 71 (ev71). the proteins of interest including prokaryotically expressed vp1 and two strains of anti-vp1 monoclonal antibody (mcab) against ev71 were covalently linked to carboxylated latex using ethyl-dimethyl-amino-propyl carbodiimide (edc) to prepare sensitized latex beads. lat was evaluated by an enzyme-linked immunosorbent assay (elisa) as a reference test. the ...201526363276
a severe case of co-infection with enterovirus 71 and vaccine-derived poliovirus type ii.enterovirus 71 (ev71) is often identified as the primary pathogen that directly leads to severe cases of hfmd, whereas the association between other enteroviruses and ev71 infection remains largely unclear. here we report a rare case of a 5-year-old boy co-infected with ev71 and vaccine-derived poliovirus (vdpv) type ii, which were identified based on pcr and sequence analysis results and clinical symptoms and were characterized on ct. we determined that the ev71 strain belongs to the c4 subtype ...201526361010
global quantitative proteomic analysis of human glioma cells profiled host protein expression in response to enterovirus type 71 infection.enterovirus 71 (ev71) is one of the leading causes of hand, foot and mouth disease with neurological complications in some cases. to study the pathogenesis of ev71 infection, large-scale analyses of ev71 infected cells have been performed. however, most of these studies employed rhabdomyosarcoma (rd) cells or used transcriptomic strategy. here, we performed silac-based quantitative proteomic analysis of ev71-infected u251 cells, a human glioma cell line. a total of 3125 host proteins were quanti ...201526350028
co-infection of enterovirus 71 and staphylococcus aureus in a 6-month-old male infant. 201526322107
analysis of ev71 infection progression using triple-silac-based proteomics approach.enterovirus 71 (ev71), a member of picornaviridae, causes severe neurological and systemic illness in children. to better understand the virus-host cell interactions, we performed a triple-silac-based quantitative proteomics study monitoring host cell proteome changes after ev71 infection. based on the quantitative data for more than 4100 proteins, ∼17% of the proteins were found as significantly changed (p<0.01) at either 8 or 20 hours post infection. five biological processes and seven protein ...201526306425
association of chemotactic chemokine ligand 5 polymorphisms with the risk of developing severe enterovirus 71 infection.respiratory damage is a main manifestation of severe enterovirus 71 (ev71) infection. polymorphisms of -403g/a (rs2107538), -28c/g (rs2280788), and in1.1t/c (rs2280789) in chemotactic chemokine ligand 5 (ccl5) have linked with many respiratory diseases. in this study, we explored the possible correlation of ccl5 polymorphisms with severe ev71 infection. blood samples were obtained from 87 children hospitalized for ev71 infection. fifty-seven healthy children were enrolled as asymptomatic control ...201526304916
complete genome sequence analysis of enterovirus 71 isolated from children with hand, foot, and mouth disease in thailand, 2012-2014.the complete genomic sequences of 14 enterovirus 71 (ev71) strains isolated from children with hand, foot, and mouth disease in thailand from 2012 to 2014 were determined and compared to enterovirus group a prototypes. phylogenetic analysis revealed that 13 strains resembled the b5 subgroup, while one strain from a fatal case designated tha_1219 belonged to the c4 subgroup. similarity plot and bootscan analyses suggested that tha_1219 underwent recombination in the p2 and p3 regions. full-genome ...201526303899
clinical features for mild hand, foot and mouth disease in china.mild hand, foot and mouth disease (hfmd) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. clinical diagnosis of mild hfmd was made by the presenting symptoms and signs (symptoms in brief) alone. we aim to evaluate the frequencies of symptoms in a retrospective case series study.201526302092
intrinsic apoptosis and proinflammatory cytokines regulated in human astrocytes infected with enterovirus 71.enterovirus 71 (ev71) has emerged as a clinically important neurotropic virus following poliovirus eradication. however, the mechanism of ev71-induced neurological manifestation remains largely unclear. in this study, we showed that human astrocytes were susceptible to ev71 and viral rna was first detected at 12 h post-infection (p.i.), whilst viral proteins were detected at 36 h p.i. ev71-infected astrocytes underwent apoptosis, in which cytochrome c was released from mitochondria to the cytoso ...201526296773
the antiviral effect of baicalin on enterovirus 71 in vitro.baicalin is a flavonoid compound extracted from scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. however, the antiviral effect of baicalin on enterovirus 71 (ev71) is still unknown. in this study, we found that baicalin showed inhibitory activity on ev71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. the expressions of ev71/3d mrna and polymerase were significantly blocked by ...201526295407
inactivated enterovirus 71 vaccine produced by 200-l scale serum-free microcarrier bioreactor system provides cross-protective efficacy in human scarb2 transgenic mouse.epidemics and outbreaks caused by infections of several subgenotypes of ev71 and other serotypes of coxsackie a viruses have raised serious public health concerns in the asia-pacific region. these concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. in this report, we present a platform for the large-scale production of a vaccine based on the inactivated ev71(e59-b4) virus. the ...201526287531
understanding enterovirus 71 neuropathogenesis and its impact on other neurotropic enteroviruses.enterovirus a71 (ev-a71) belongs to the species group a in the enterovirus genus within the picornaviridae family. ev-a71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. the pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. ev-a71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly ...201526276025
immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates.a vaccine against human enterovirus 71 (ev-a71) is urgently needed to combat outbreaks of ev-a71 and in particular, the serious neurological complications that manifest during these outbreaks. in this study, an ev-a71 virus-like-particle (vlp) based on a b5 subgenogroup (ev-a71-b5 vlp) was generated using an insect cell/baculovirus platform. biochemical analysis demonstrated that the purified vlp had a highly native procapsid structure and initial studies in vivo demonstrated that the vlps were ...201526271825
construction and characterization of infectious cdna clones of enterovirus 71 (ev71). 201526271283
replication and inhibitors of enteroviruses and parechoviruses.the enterovirus (ev) and parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, ev-a71, ev-d68, and human parechoviruses (hpev). they cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. at the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all evs and hpevs due to the great number o ...201526266417
norepinephrine and epinephrine enhanced the infectivity of enterovirus 71.enterovirus 71 (ev71) infections may be associated with neurological complications, including brainstem encephalitis (be). severe ev71 be may be complicated with autonomic nervous system (ans) dysregulation and/or pulmonary edema (pe). ans dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.201526252639
enterovirus71 virus-like particles produced from insect cells and purified by multistep chromatography elicit strong humoral immune responses in mice.the study aims to develop a novel multistep chromatographic purification process for human enterovirus71 virus-like particles (vlps) produced from insect cells (sf9) infected with recombinant baculovirus.201526248815
[expression of ev71-vp1, psgl-1 and scarb2 in tissues of infants with brain stem encephalitis].to understand the correlation of enterovirus 71 (ev71), p-selectin glycoprotein ligand-1 (psgl-1), and scavenger receptor b2 (scarb2) and to explore the possible pathway and mechanism of ev71 infection by observing the expression of ev71, psgl-1 and scarb2 in tissues of infants with brain stem encephalitis.201526245084
australian national enterovirus reference laboratory annual report, 2013.australia conducts surveillance for cases of acute flaccid paralysis (afp) in children less than 15 years of age as the main method to monitor its polio-free status in accordance with the world health organization (who) recommendations. cases of afp in children are notified to the australian paediatric surveillance unit or the paediatric active enhanced disease surveillance system and faecal specimens are referred for virological investigation to the national enterovirus reference laboratory. in ...201526234257
human enterovirus nonstructural protein 2catpase functions as both an rna helicase and atp-independent rna chaperone.rna helicases and chaperones are the two major classes of rna remodeling proteins, which function to remodel rna structures and/or rna-protein interactions, and are required for all aspects of rna metabolism. although some virus-encoded rna helicases/chaperones have been predicted or identified, their rna remodeling activities in vitro and functions in the viral life cycle remain largely elusive. enteroviruses are a large group of positive-stranded rna viruses in the picornaviridae family, which ...201526218680
nuclear protein sam68 interacts with the enterovirus 71 internal ribosome entry site and positively regulates viral protein translation.enterovirus 71 (ev71) recruits various cellular factors to assist in the replication and translation of its genome. identification of the host factors involved in the ev71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. in this study, we demonstrated that the cellular factor 68-kda src-associated protein in mitosis (sam68) acts as an internal ribosome entry site (ires) trans-ac ...201526202240
quinolizidine alkaloids reduced mortality in ev71-infected mice by compensating for the levels of t cells.recent outbreak of hand, foot and mouse disease caused by enterovirus 71 is a serious threat to infants and children in asia-pacific countries. no vaccines or antiviral therapies are available against this infection. in this study, we found that quinolizidine alkaloids could improve the levels of t cells in mice. the structure-activity relationships demonstrated that the oxidation and double bonds are important for the excellent potency. oxysophocarpine, the most effective compound of six quinol ...201526189894
development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human enterovirus-71 vaccine encapsulated carrier.this study introduces a new approach for enhancing immunity toward mucosal vaccines. hev71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific iga & igg levels and viral neutralizing antibody titers. the antibody responses induced in rabbits by the different formulations delivered by a sing ...201526186664
the role of vp1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a cynomolgus monkey model.enterovirus 71 (ev71), a major causative agent of hand, foot, and mouth disease, occasionally causes severe neurological symptoms. we identified p-selectin glycoprotein ligand-1 (psgl-1) as an ev71 receptor and found that an amino acid residue 145 in the capsid protein vp1 (vp1-145) defined psgl-1-binding (pb) and psgl-1-nonbinding (non-pb) phenotypes of ev71. however, the role of psgl-1-dependent ev71 replication in neuropathogenesis remains poorly understood. in this study, we investigated vir ...201526181772
broad protection with an inactivated vaccine against primary-isolated lethal enterovirus 71 infection in newborn mice.circulating enterovirus 71 (ev-a71)-associated hand, foot, and mouth disease is on the rise in the asian-pacific region. although animal models have been developed using mouse-adapted ev-a71 strains, mouse models using primary ev-a71 isolates are scarce. lethal animal models with circulating ev-a71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation.201526169371
[molecular mechanism of action of hnrnp k and rtn3 in the replication of enterovirus 71].enterovirus 71 (ev71) is a neurotropic pathogen that can induce hand, foot and mouth disease in children. there is an appreciable mortality rate after ev71 infections. the mechanism of action of ev71 replication is not known. recent work has identified some of cell factors of the host that participate in the synthesis of the rna and proteins of ev71 (e.g., hnrnp k, reticulon 3 (rtn 3)). in that work, researchers used a competitive assay to show that hnrnp k can interact with ev71 5' utr, which i ...201526164948
[research into the pathogenicity of enterovirus 71].enterovirus 71 (ev71) is a major causative agent of hand, foot and mouth disease (hfmd). belongs to family picornaviridae, genus enterovirus, species a. ev71 infection usually affects subjects aged <5 years. hfmd caused by ev71 infection is usually mild in children. however, in some cases ev71 infection can lead to severe neurogenic disease and even death. ev71 infection has caused epidemic worldwide (especially in the asia pacific). hfmd caused by ev71 has become a major public-health prol lem ...201526164947
[enterovirus sequencing as a new approach to the laboratory diagnosis for clinical and epidemiological purposes].introducing enterovirus sequencing as an advanced approach to classify the viruses isolated according to the novel nomenclature and to characterize isolates in detail.201526099615
an enterovirus 71 strain causes skeletal muscle damage in infected mice.to study the target organs for enterovirus 71 (ev71) in infected suckling mice.201526097530
antiviral potential of a novel compound cw-33 against enterovirus a71 via inhibition of viral 2a protease.enterovirus a71 (ev-a71) in the picornaviridae family causes hand-foot-and-mouth disease, aseptic meningitis, severe central nervous system disease, even death. ev-a71 2a protease cleaves type i interferon (ifn)-α/β receptor 1 (ifnar1) to block ifn-induced jak/stat signaling. this study investigated anti-ev-a7l activity and synergistic mechanism(s) of a novel furoquinoline alkaloid compound cw-33 alone and in combination with ifn-β anti-ev-a71 activities of cw-33 alone and in combination with if ...201526090728
hand-foot-and-mouth disease: a new look at a classic viral rash.hand-foot-and-mouth disease (hfmd) is a common cause of viral rash in children with classic skin findings which are easily recognized by pediatricians. recently, several atypical cutaneous manifestations of hfmd have been described. awareness of these patterns may lead providers to appropriate diagnosis and management. this review also highlights the epidemiological patterns of more virulent strains and emerging research in disease prevention.201526087425
phylodynamics of enterovirus a71-associated hand, foot, and mouth disease in viet nam.enterovirus a71 (ev-a71) is a major cause of hand, foot, and mouth disease (hfmd) and is particularly prevalent in parts of southeast asia, affecting thousands of children and infants each year. revealing the evolutionary and epidemiological dynamics of ev-a71 through time and space is central to understanding its outbreak potential. we generated the full genome sequences of 200 ev-a71 strains sampled from various locations in viet nam between 2011 and 2013 and used these sequence data to determ ...201526085170
[detection of cerebrospinal fluid anti-enterovirus 71 igm in children with severe hand, food and mouth disease induced by enterovirus 71 infection and its clinical significance].to detect the anti-enterovirus 71 (ev71) igm level in cerebrospinal fluid (csf) of children with severe hand, foot and mouth disease (hfmd) induced by ev71 and then analyze the relationships among the igm antibody levels, csf routine examination and patients' clinical features, and thus to evaluate the clinical significance of anti-ev71 igm as a new indicator for early diagnosis of children with severe hfmd induced by ev71.201526080665
anti-viral and cytotoxic norbisabolane sesquiterpenoid glycosides from phyllanthus emblica and their absolute configurations.in an effort to identify anti-viral and cytotoxic compounds from phyllanthus spp., 14 highly oxygenated norbisabolane sesquiterpenoids, phyllaemblicins h1-h14, were isolated from the roots of phyllanthus emblica linn, along with phyllaemblicins b and c and glochicoccinoside d. their structures were determined on the basis of detailed spectroscopic analysis and chemical methods. determination of absolute configurations of these compounds was facilitated by theoretical calculations of electronic c ...201526074492
cytokine responses and correlations thereof with clinical profiles in children with enterovirus 71 infections.severe complications associated with ev71 infections caused many infants death. however, the pathogenesis of ev71 infection in the severe cases remained poorly understood.201526058678
validation and utilization of an internally controlled multiplex real-time rt-pcr assay for simultaneous detection of enteroviruses and enterovirus a71 associated with hand foot and mouth disease.hand foot and mouth disease (hfmd) is a disease of public health importance across the asia-pacific region. the disease is caused by enteroviruses (evs), in particular enterovirus a71 (ev-a71). in ev-a71-associated hfmd, the infection is sometimes associated with severe manifestations including neurological involvement and fatal outcome. the availability of a robust diagnostic assay to distinguish ev-a71 from other evs is important for patient management and outbreak response.201526050791
monoclonal neutralizing antibodies against ev71 screened from mice immunized with yeast-produced virus-like particles.periodic outbreaks of hand, foot and mouth disease (hfmd) occur in children under 5 years old, and can cause death in some cases. the c4 strain of enterovirus 71 (ev71) is the main pathogen that causes hfmd in china. although no drugs against ev71 are available, some studies have shown that candidate vaccines or viral capsid proteins can produce anti-ev71 immunity. in this study, female babl/c mice (6-8 weeks old) were immunized with virus-like particles (vlps) of ev71 produced in yeast to scree ...201526040893
dynamic constitution of the pathogens inducing encephalitis in hand, foot and mouth disease in kunming, 2009-2011.hand, foot and mouth disease (hfmd), caused by various viral pathogens, is an emerging infectious disease in children in asia. understanding the composition of these pathogens is necessary to prevent and control this disease. in the present study, the pathogens in 436 hfmd patients (from 2009 to 2011) with concurrent clinical indications of encephalitis, meningoencephalitis, or both, were defined using the semi-nested pcr. a systematic analysis of the composition of these pathogens was performed ...201525866107
crystal structures of yeast-produced enterovirus 71 and enterovirus 71/coxsackievirus a16 chimeric virus-like particles provide the structural basis for novel vaccine design against hand-foot-and-mouth disease.human enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the two major causative agents for hand-foot-and-mouth disease (hfmd). previously, we demonstrated that a virus-like particle (vlp) for ev71 produced from saccharomyces cerevisiae is a potential vaccine candidate against ev71 infection, and an ev71/cva16 chimeric vlp can elicit protective immune responses against both virus infections. here, we presented the crystal structures of both vlps, showing that both the linear and conformati ...201525833050
comparative pathogenicity of coxsackievirus a16 circulating and noncirculating strains in vitro and in a neonatal mouse model.an enterovirus 71 (ev71) vaccine for the prevention of hand, foot, and mouth disease (hmfd) is available, but it is not known whether the ev71 vaccine cross-protects against coxsackievirus (cv) infection. furthermore, although an inactivated circulating cva16 changchun 024 (cc024) strain vaccine candidate is effective in newborn mice, the cc024 strain causes severe lesions in muscle and lung tissues. therefore, an effective cv vaccine with improved pathogenic safety is needed. the aim of this st ...201525831207
enterovirus-specific anti-peptide antibodies.enterovirus 71 (ev-71) is the main causative agent of hand, foot, and mouth disease (hfmd) which is generally regarded as a mild childhood disease. in recent years, ev71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in asia. a formalin-inactivated ev71 whole virus vaccine has completed phase iii trial in china but is currently unavailable clinically. the high cost of manufacturing and supply problems may limit p ...201526424285
epidemiological characteristics and spatial-temporal clusters of hand, foot, and mouth disease in zhejiang province, china, 2008-2012.hand, foot and mouth disease (hfmd) is one of the major public health concerns in china. being the province with high incidence rates of hfmd, the epidemiological features and the spatial-temporal patterns of zhejiang province were still unknown. the objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. the surveillance data of hfmd during 2008-2012 were collected from the communicable disea ...201526422015
molecular epidemiology of an outbreak of hand, foot, and mouth disease associated with subgenotype c4a of enterovirus a71 in nanchang, china in 2014.an outbreak of hand, foot, and mouth disease was reported through hospital-based surveillance in nanchang, china in 2014. a total of 244 cases were reported, 176 (72.1%) cases were tested positive for enteroviruses by direct reverse transcription-polymerase chain reaction, in which enterovirus a71 (ev-a71), coxsackievirus a16 (cv-a16), and untyped enteroviruses (uev) accounted for 84.1%, 3.4%, and 12.5%, respectively. in this outbreak, children under 5 years old constituted more than 98% of the ...201526058813
phylogenetic analysis of the major causative agents of hand, foot and mouth disease in suzhou city, jiangsu province, china, in 2012-2013.hand, foot and mouth disease (hfmd) is a serious public health problem that has emerged over the past several decades. pathogen detection by the chinese national hfmd surveillance system has focused mainly on enterovirus 71 (ev71) and coxsackievirus a16 (ca16). therefore, epidemiological information regarding the other causative enteroviruses is limited. to identify the pandemic enterovirus in suzhou, jiangsu province, china, clinical samples from patients with hfmd were collected from 2012 to 2 ...201526038764
seroepidemiology of coxsackievirus a6, coxsackievirus a16, and enterovirus 71 infections among children and adolescents in singapore, 2008-2010.coxsackieviruses a6 (cv-a6) and a16 (cv-a16) and enterovirus 71 (ev-a71) have caused periodic epidemics of hand, foot and mouth disease (hfmd) among children in singapore. we conducted a cross-sectional study to estimate the seroprevalence of these enteroviruses among singapore children and adolescents. the study was conducted between august 2008 and july 2010. it involved 700 singapore residents aged 1-17 years whose residual sera were obtained following the completion of routine biochemical in ...201526011735
enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated enterovirus a71 vaccine in jiangsu, china, 2012-2013.epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. an active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in jiangsu province from 2012 to 2013. fifty-nine infants were randomly selected from 522 non-ev-a71/cv-a16 hfmd patients. we collected 173 throat swabs and 174 rectal swabs from these infants. rt-pcr was used to ampl ...201526010334
construction and characterization of an infectious cdna clone of echovirus 25.echovirus 25 (e-25) is a member of the enterovirus family and a common pathogen that induces hand, foot, and mouth disease (hfmd), meningitis, skin rash, and respiratory illnesses. in this study, we constructed and characterized an infectious full-length e-25 cdna clone derived from the xm0297 strain, which was the first subgenotype d6 strain isolated in xiamen, china. the 5'-untranslated regions (5'-utr), p3 (3a-3b, 3d) and p3 (3c) regions of this e-25 (xm0297) strain were highly similar to ev- ...201526004198
cellular proteome alterations in response to enterovirus 71 and coxsackievirus a16 infections in neuronal and intestinal cell lines.hand, foot and mouth disease is mainly caused by enterovirus a71 (ev-a71) and coxsackievirus a16 (cv-a16), but ev-a71 is also associated with severe neurological complications. host factors may contribute to the different clinical outcomes of ev-a71 and cv-a16 infections. a neurovirulent ev-a71 strain (ev-a71/uh1) from a fatal case, a non-neurovirulent ev-a71 strain (ev-a71/sha66) and a cv-a16 strain (cv-a16/22159) from cases of uncomplicated hfmd were used. replication of the viruses in sk-n-mc ...201526003530
the epidemiological study of coxsackievirus a6 revealing hand, foot and mouth disease epidemic patterns in guangdong, china.enterovirus a71 (eva71) and coxsackievirus a16 (cva16) are regarded as the two major causative pathogens in hand, foot and mouth disease (hfmd) epidemics. however, cva6, previously largely ignored, became the predominant pathogen in china in 2013. in this study, we describe the epidemiological trends of cva6 during the annual hfmd outbreaks from 2008 to 2013 in guangdong, china. the study results show that cva6 has been one of three major causative agents of hfmd epidemics since 2009. the period ...201525993899
microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse-transcription polymerase chain reaction for the rapid detection of enterovirus 71 and coxsackievirus a16 in throat swab specimens.enterovirus 71 and coxsackievirus a16 are the main pathogens causing hand-foot-mouth disease. in this paper, microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse transcript-polymerase chain reaction has been developed for the detection of enterovirus 71 and coxsackievirus a16 in throat swab specimens. the specific reverse transcription-polymerase chain reaction amplicons labeled with sybr orange were separated by microchip capillary electropho ...201525953405
characterization of severe hand, foot, and mouth disease in shenzhen, china, 2009-2013.hand, foot, and mouth disease (hfmd) is caused by human enteroviruses, especially by enterovirus 71 (ev71) and coxsackievirus a16 (ca16). patients infected with different enteroviruses show varied clinical symptoms. the aim of this study was to determine whether the etiological spectrum of mild and severe hfmd changed, and the association between pathogens and clinical features. from 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. a dynami ...201525951788
two models for changes of ev71 immunity in infants and young children.human enterovirus 71 (ev71) has been associated with outbreaks of hand-foot-and-mouth disease (hfmd) in china. susceptibility to ev71 is associated with age, but few studies have been accomplished to measure such a relationship. a better understanding of the connection between susceptibility and age is necessary to develop strategies for control of hfmd. in 2010, a survey of an epidemic of ev71 was conducted in a northern city of jiangsu province in china. samples were tested serologically to id ...201525906390
[prevalence and analyses of the changing etiology of hand, foot and mouth disease in china].hand, foot, and mouth disease (hfmd) is a viral infectious disease regarded to be a public-health problem worldwide. since the 1990s, hfmd began to spread in the asia-pacific region (especially in south-east asia). hfmd outbreaks have occurred in mainland china frequently since 2008, and the morbidity and mortality of hfmd has continued to increase in recent years. in mainland china, enterovirus a serotype enterovirus a71 (ev-a71) and coxsackievirus a16 (cva16) have been the major pathogens of h ...201526738295
[pathogenic and clinical presentation of bullous rash in hand, foot and mouth disease].to investigate the pathogenic and clinical presentation and laboratory tests of bullous rash in hand, foot and mouth disease (hfmd) in xi'an from january 2013 to december 2014 by retrospective analysis.201526717661
clinical and etiological characteristics of atypical hand-foot-and-mouth disease in children from chongqing, china: a retrospective study.hand-foot-and-mouth disease (hfmd) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. to date, no study has been conducted to report the clinical and epidemiological characteristics of atypical hfmd.201526693489
efficacy of a trivalent hand, foot, and mouth disease vaccine against enterovirus 71 and coxsackieviruses a16 and a6 in mice.hand, foot, and mouth disease (hfmd) has recently emerged as a major public health concern across the asian-pacific region. enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the primary causative agents of hfmd, but other members of the enterovirus a species, including coxsackievirus a6 (cva6), can cause disease. the lack of small animal models for these viruses have hampered the development of a licensed hfmd vaccine or antivirals. we have previously reported on the development of a mous ...201526593938
the antiviral and antimicrobial activities of licorice, a widely-used chinese herb.licorice is a common herb which has been used in traditional chinese medicine for centuries. more than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral, antimicrobial, anti-inflammatory, antitumor and other activities. this paper provides a summary of the antiviral and antimicrobial activities of licorice. the active components and the possible mechanisms for th ...201526579460
[infection status of enterovirus 71 and coxsackievirus a16 among children receiving health examination for child care setting entrance in beijing and their related medical care seeking practice].to understand the infection status of enterovirus 71 (ev71) and coxsackievirus a16 (cox a16) among children receiving health examination for child care setting entrance in beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease (hfmd).201526564703
etiology of multiple non-ev71 and non-cva16 enteroviruses associated with hand, foot and mouth disease in jinan, china, 2009-june 2013.hand, foot, and mouth disease (hfmd) is an infectious disease caused by human enterovirus 71 (ev71), coxsackievirus a16 (cva16) and other enteroviruses. it is of interest that other enteroviruses associated with hfmd in jinan have been rarely reported. the aim of the present study is to detect and characterize the circulating serotypes of non-ev71 and non-cva16 enteroviruses associated with hfmd in jinan city, shandong province, china. a total of 400 specimens were collected from clinically diag ...201526562154
time series analysis of reported cases of hand, foot, and mouth disease from 2010 to 2013 in wuhan, china.hand, foot, and mouth disease (hfmd) is an infectious disease caused by a group of enteroviruses, including coxsackievirus a16 (cva16) and enterovirus a71 (ev-a71). in recent decades, asian countries have experienced frequent and widespread hfmd outbreaks, with deaths predominantly among children. in several asian countries, epidemics usually peak in the late spring/early summer, with a second small peak in late autumn/early winter. we investigated the possible underlying association between the ...201526530702
a new ev71 vp3 epitope in norovirus p particle vector displays neutralizing activity and protection in vivo in mice.enterovirus 71 (ev71) and coxsackievirus a16 (cva16), as the main agents causing hand, foot and mouth disease (hfmd), have become a serious public health concern in the asia-pacific region. recently, various neutralizing b cell epitopes of ev71 were identified as targets for promising vaccine candidates. structural studies of picornaviridae indicated that potent immunodominant epitopes typically lie in the hypervariable loop of capsid surfaces. however, cross-neutralizing antibodies and cross-pr ...201526529072
potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or coxsackievirus a16.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the two major causative agents of hand, foot and mouth disease (hfmd), for which there are currently no licenced treatments. here, the acquisition of resistance towards two novel capsid-binding compounds, nld and ald, was studied and compared to the analogous compound gpp3. during serial passage, ev71 rapidly became resistant to each compound and mutations at residues i113 and v123 in vp1 were identified. a mutation at residue 113 was also ...201526522770
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