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Selection and characterization of vaccine strain for Enterovirus 71 vaccine development.Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in Asia because effective medications and prophylactic vaccine against EV71 infection are not available. Based on the success of inactivated poliovirus vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could be developed. Identification of EV71 vaccine strain which can grow to high titer in Vero cell and induce cross-genotype virus neutralizing antibody responses represents the first step in vac ...201122142585
seroprevalence of enterovirus 71 and no evidence of crossprotection of enterovirus 71 antibody against the other enteroviruses in kindergarten children in taipei city.background/purpose: enterovirus 71 (ev71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. this study is to investigate the seroprevalence and seroconversion of ev71, and the crossprotection of ev71 antibody against other enteroviruses among kindergarteners. methods: overall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in taipei, taiwan and we measured their ev71 neutralizing antibody. wh ...201122154997
detection of enterovirus 71 using reverse transcription loop-mediated isothermal amplification (rt-lamp).reverse transcription loop-mediated isothermal amplification (rt-lamp), which is a visual assay for nucleic acids, is performed in a single step using one tube at 65°c for 1.5h. in this study, rt-lamp was established as a method for the detection of enterovirus 71 (ev71). the detection limit of the assay was approximately 10 copies, and no cross-reactivity was noted with coxsackievirus a16, echovirus, human rotavirus (hrv) or norovirus. this assay, which offers greater sensitivity at a lower cos ...201122155579
epidemic characteristics of hand, foot, and mouth disease in shanghai from 2009 to 2010: enterovirus 71 subgenotype c4 as the primary causative agent and a high incidence of mixed infections with coxsackievirus a16.background: enterovirus 71 (ev71) has been the main causative agent of hand, foot, and mouth disease (hfmd) outbreaks in recent years. a significant increase in the number of hfmd cases in china over the last 3 y has made the public prevention and therapy of this disease a critical issue. methods: a total of 3208 hfmd patients in shanghai during the period 2009 to 2010 were analyzed; 437 clinical specimens were collected for the determination of causative pathogens. eight of the isolated ev71 st ...201122176514
[experts consensus on rescue and treatment of severe cases with enterovirus 71 (ev71) infection]. 201122176902
in vitro inhibition of influenza virus infection by a crude extract from isatis indigotica root resulting in the prevention of viral attachment.isatis indigotica root (iir) has been widely used as a chinese medicinal herb to treat regular seasonal influenza over the long history of traditional chinese medicinal practice. however, its inhibitory activities against influenza virus infections along with the associated mechanisms have not been investigated comprehensively. in this study, the chemical nature, mode of action and in vitro anti-influenza activities of a crude extract ( ...201122179315
diffusion-weighted imaging in the diagnosis of enterovirus 71 encephalitis.backgroundin the early phase of viral encephalitis, conventional mri may appear normal. diffusion-weighted imaging (dwi) is a sensitive tool for detecting early changes in cellular function in the central nervous system.purposeto investigate the usefulness of dwi in the diagnosis of enterovirus 71 (ev71) encephalitis, and to determine whether dwi is superior to conventional mr sequences.material and methodsmri scans in 26 patients were retrospectively evaluated for distribution of lesions on t1- ...201122184685
?Fighting against infectious diseases in China.Dr. Yin started his research on infectious disease prevention in the 1980s. In 1985, Dr. Yin sucessfully isolated the hepatitis A virus, after which, in 2002, he developed the first proprietary inactivated hepatitis A vaccine in China and soon launched it into the China market. Led by Dr. Yin, Sinovac successfully developed the vaccine prducts against SARS, H5N1, H1N1, hepatitis A and B and infleunza. Currently, Sinovac is working on the R&D of EV71 vaccine against hand, foot and mouth disease, ...201122185808
transgenic expression of human p-selectin glycoprotein ligand-1 is not sufficient for enterovirus 71 infection in mice.human psgl-1 is a receptor for ev71 that facilitates ev71 entry and replication in mouse cells. we have evaluated the role of human psgl-1 in ev71 infection in vivo using a transgenic mouse line. expression of human psgl-1 failed to enhance infectivity of clinical ev71 strains in mice; however, it promoted replication and symptom severity at an earlier stage in mice upon infection with a mouse-adapted ev71 strain. we therefore conclude that human psgl-1 alone is not sufficient to modulate infect ...201122187102
influence of vitamin a status on the antiviral immunity of children with hand, foot and mouth disease.background & aims: vitamin a (va) deficiency has been shown to affect antiviral immunity and thus may be related to the progress and outcome of hand, foot and mouth disease (hfmd) in young children. our objective was to determine whether children with hfmd associated with va insufficiency displayed a decline in antiviral immunity. methods: 450 children with hfmd and 113 non-infected children were included in this study. dietary investigations were performed using a 24-h dietary questionnaire. th ...201122197454
Hand, Foot and Mouth Disease in Yunnan Province, China, 2008-2010.This study was done to assess the epidemic features of hand, foot and mouth disease in Yunnan Province. Surveillance data from the beginning of 2008 through the end of 2010 were analyzed to conduct the demographic data of patients and morbidity as well as the estimation between possible risk factors for severe or fatal cases. Of the 75109 cases reported, laboratory tests confirmed 3691 cases. Thus, the average annual incidence proportion was 55 per 100000 population with a total case fatality ra ...201122199158
MRI and associated clinical characteristics of EV71-induced brainstem encephalitis in children with hand-foot-mouth disease.INTRODUCTION: This study was conducted to investigate MRI and associated clinical characteristics of brainstem encephalitis induced by enterovirus 71 (EV71) in children with hand-foot-mouth disease (HFMD). METHODS: We analyzed clinical and imaging data from 42 HFMD cases with EV71-induced brainstem encephalitis. All patients underwent plain and enhanced MRI cranial scans and were placed into one of two groups acc ...201122200974
the association of recombination events in the founding and emergence of subgenogroup evolutionary lineages of human enterovirus 71.enterovirus 71 (ev71) is responsible for frequent large scale outbreaks of hand, foot and mouth disease worldwide, and represent a major aetiological agent of severe, sometime fatal neurological disease. ev71 variants have been classified into three genogroups (gga, ggb, ggc), the latter two further subdivided into subgenogroups, b1-b5 and c1-c5. to investigate the dual roles of recombination and evolution in the epidemiology and transmission of ev71 worldwide, we performed a large scale genetic ...201122205739
enterovirus type 71 neutralizing antibodies in the serum of macaque monkeys immunized with ev71 virus-like particles.enterovirus type 71 (ev71) is a virulent form of enteroviruses causing hospitalizations for children less than three years of age. currently there are no anti-viral therapies or vaccines available for ev71. due to the high risk of poliomyelitis-like paralysis and fatal encephalitis, an effective vaccine to ev71 could potentially prevent virus-induced morbidity and mortality. in this study, we first tested a potential ev71 vaccine candidate based on virus-like particles (vlp). we vaccinated macaq ...201122214888
detection of human enterovirus 71 and coxsackievirus a16 in children with hand, foot and mouth disease in china.the aims of the present study were to investigate the genetic characteristics of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) strains in china and to evaluate the relationship between the genotypes of cva16 and ev71 and their geographical distribution. a total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (hfmd) in zhejiang province. the presence of enteroviruses was determined ...201222218731
molecular determinants of enterovirus 71 viral entry: cleft around gln-172 on vp1 protein interacts with variable region on scavenge receptor b 2.enterovirus 71 (ev71) is one of the major pathogens that cause hand, foot, and mouth disease outbreaks in young children in the asia-pacific region in recent years. human scavenger receptor class b 2 (scarb2) is the main cellular receptor for ev71 on target cells. the requirements of the ev71-scarb2 interaction have not been fully characterized, and it has not been determined whether scarb2 serves as an uncoating receptor for ev71. here we compared the efficiency of the receptor from different s ...201222219187
characterization of a monoclonal antibody against the 3d polymerase of enterovirus 71 and its use for the detection of human enterovirus a infection.over the last decade, frequent epidemic outbreaks of hand, foot and mouth disease have been observed in the asia-pacific region. hand, foot and mouth disease is caused by different viruses from the enterovirus family, mainly coxsackievirus a16 and enterovirus 71 (ev71) from the human enterovirus a family. severe disease and neurological complications are associated more often with ev71 infection, and can lead occasionally to fatal brain stem encephalitis in young children. the rapid progression ...201122226793
distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications.abstract: background: to explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (hfmd) complicated with nervous system disease. 234 hospitalized hfmd patients treated in shengjing hospital, liaoning province were analyzed retrospectively. based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. based on the detected p ...201222230340
evaluation of human enterovirus 71 and coxsackievirus a16 specific immunoglobulin m antibodies for diagnosis of hand-foot-and-mouth disease.abstract: background: hand-foot-and-mouth disease (hfmd) is caused mainly by the human enterovirus type 71 (hev71) and the coxsackievirus a group type 16 (cva16). large outbreaks of disease have occurred frequently in the asia-pacific region. reliable methods are needed for diagnosis of hfmd in childen. igm-capture elisa, with its notable advantages of convenience and low cost, provides a potentially frontline assay. we aimed to evaluate the newly developed igm-capture elisas for hev71 and cva1 ...201222234169
enterovirus 71 encephalomyelitis and japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and rna.to investigate if two important epidemic viral encephalitis in children, enterovirus 71 (ev71) encephalomyelitis and japanese encephalitis (je) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished.201222236252
detection and characterization of enterovirus associated with herpangina and hand, foot, and mouth disease in seoul, korea.human enteroviruses (hevs) are a major cause of herpangina, hfmd (hand, foot, and mouth disease), and other neurological diseases in seoul, korea.201122239028
in vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection.enterovirus 71(ev71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. more effective antiviral drugs are needed to prevent or reduce ev71-related disease and complications. however, there are no standard models currently in use to evaluate activity against ev71 infection both in vitro and in vivo. in this study, the activity of ribavirin and pleconaril against ev71 infection was evaluated in two models. an in vitro e ...201222245989
mri findings of neurological complications in hand-foot-mouth disease by enterovirus 71 infection.to explore the imaging characterization of neurological complications associated with the enterovirus 71 (ev71) epidemics.201222248036
detection of human enterovirus 71 reverse transcription loop-mediated isothermal amplification (rt-lamp).aims:  in this study, a one-step, single-tube reverse transcription loop-mediated isothermal amplification (rt-lamp) assay was developed and validated for the detection of human enterovirus 71 (ev71), the major aetiological agent of hand, foot and mouth disease (hfmd). methods and results:  reverse transcription loop-mediated isothermal amplification assay was optimized to amplify vp1 gene in the presence of a specific primer set and bst dna polymerase at an isothermal temperature of 63°c for 1  ...201222256968
enterovirus 71 disrupts interferon signaling by reducing the interferon receptor i.the recent outbreak of enterovirus 71 (ev71) infected millions of children and caused over 1,000 deaths. to date, neither effective vaccine nor antiviral treatment is available for ev71 infection. interferons (ifns) have been successfully applied for treating patients such as hepatitis b and c viral infections for decades but failed to treat ev71 infections. here, we provide the evidence that ev71 antagonizes type i ifn signaling by reducing the level of interferon receptor 1 (ifnar1). we show t ...201222258259
[recent advances in reverse genetics of enterovirus 71]. 201122263276
association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease.enterovirus 71 (ev71) is one of the common causative agents of hand, foot and mouth disease (hfmd), and is associated with several outbreaks with neurological complications including encephalitis. this study investigated the polymorphisms of interferon gamma (ifn-γ)+874 t/a and interleukin 10 (il-10)-1082 g/a in 65 chinese patients with ev71 encephalitis and 113 chinese hfmd patients without complications. the polymorphisms of ifn-γ+874 t/a and il-10-1082 g/a were determined by polymerase chain ...201222263663
enterovirus 71 viral capsid protein linear epitopes: identification and characterization.to characterize the human humoral immune response against enterovirus 71 (ev71) infection and map human epitopes on the viral capsid proteins.201222264266
seroepidemiology of enterovirus 71 infection prior to the 2011 season in children in shanghai.in 2010, china experienced the largest outbreak on record of enterovirus 71 (ev71)-associated hand foot and mouth disease (hfmd) with more than 1.7 million cases, 27,000 patients with severe neurological complications and 905 deaths. understanding of the seroprevalence of neutralizing antibodies (nab) against ev71 and their protective role against hfmd in children is crucial for the implementation of future therapeutic and prophylactic intervention.201222265829
genetic analysis of the p1 region of human enterovirus 71 strains and expression of the 55 f strainvp1 protein.enterovirus 71 (ev71) is a member of the entero-virus genus of the picornaviridae family and is the major cause of hand, foot, and mouth disease (hfmd) in children. different strains from gansu were cloned and the p1 protein was sequenced and analysed. results indicate that there are three kinds of ev71 infections prevalent in gansu. the vp1 protein from one of these strains, 55f, was expressed. the recombinant protein was expressed with high level and reacted specifically with the ev71 patient ...201222270802
characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection.enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease (hfmd) and is associated with severe neurologic complications and mortalities. at present, there is no vaccine or therapeutic available for treatment.201222279543
major vault protein: a virus-induced host factor against viral replication through the induction of type-i interferon.major vault protein (mvp) is the major constituent of vaults and is involved in multidrug resistance, nucleocytoplasmic transport, and cell signaling. however, little is known about the role of mvp during viral infections. in this study, high levels of mvp were found in peripheral blood mononuclear cells, sera, and liver tissue from patients infected with hepatitis c virus (hcv) relative to healthy individuals. hcv infections resulted in elevated levels of mvp messenger rna (mrna) and protein ex ...201222318991
screening and detection of human enterovirus 71 infection by a real-time rt-pcr assay in marseille, france, 2009-2011.enterovirus-positive samples diagnosed in marseille (january 2009 to september 2011) were screened for ev71 by real-time rt-pcr. ev71 was detected in three children below the age of 2 years with no history of overseas travel; two of these cases were associated with severe clinical presentation. viruses demonstrated genetic similarity to other european genogroup c2 strains. strain mrs/09/3663 complete sequencing revealed 97.6% identity across the entire genome with a 2008 singapore isolate, witho ...201222332991
[acute kidney injury in critically ill children infected with influenza a virus (h1n1) and enterovirus 71].to analyze the clinical characteristics of acute kidney injury (aki) in critically ill childhood patients with influenza a virus (h1n1) and enterovirus 71 (ev71), and to study the significance of the serum creatinine and urine output in diagnosis of aki.201122336307
[analysis on detection of enterovirus nucleotides in feces samples of hand-foot-mouth disease patients after recovery].to explore the duration of enterovirus (ev) nucleotides positive in feces samples of hand-foot-mouth disease (hfmd) patients after recovery.201122336339
molecular characterization of human enteroviruses in the central african republic: uncovering wide diversity and identification of a new human enterovirus a71 genogroup.human enteroviruses (hev) are among the most common viruses infecting humans. their circulation has been widely studied in most parts of the world but not in sub-saharan africa, where poliomyelitis remains prevalent. we report here the molecular characterization of 98 nonpoliovirus (non-pv) hev strains isolated from 93 randomly selected cell culture-positive supernatants from stool samples collected from 1997 through 2006 from children with acute flaccid paralysis living in the central african r ...201222337981
[a pathogen analysis within 174 cases of hand-foot-mouth disease in the summer of 2009].to analyze the pathogen and characteristics of the serum types of enterovirus of hand-foot-and-mouth disease (hfmd) in the summer, 2009.201122338230
antiviral effect of geraniin on human enterovirus 71 in vitro and in vivo.human enterovirus 71 infection causes hand, foot and mouth disease in children under 6 years of age and has caused mortalities in large-scale outbreaks in the asia-pacific region. no effective vaccine or antiviral drugs currently exist against enterovirus 71 in the clinic. in this study, we investigated the antiviral effect of geraniin on enterovirus 71 both in vitro and in vivo. the results showed that geraniin effectively inhibited virus replication in rhabdomyosarcoma cells with an ic(50) of ...201222342145
[experimental studies on infant tupaia belangeri chineses with ev71 infection].tupaia belangeri are small mammals with a squirrel-like appearance; they were formerly classified under the primates order despite the lack of derived features characteristic of primates. given that t. belangeri are easy to raise, cheap to maintain, and have a small body size, a high reproductive rate, and close affinity to primates, these animals would be used as an alternative to primates in biomedical research. three-month old t. belangeri chineses were infected with enterovirus 71 (ev71) via ...201222345002
incidence rates of enterovirus 71 infections in young children during a nationwide epidemic in taiwan, 2008-09.enterovirus 71 (ev71) is causing life-threatening outbreaks in tropical asia. in taiwan and other tropical asian countries, although nationwide ev71 epidemics occur cyclically, age-specific incidence rates of ev71 infections that are critical to estimate disease burden and design vaccine trials are not clear. a nationwide ev71 epidemic occurred in 2008-09 in taiwan, which provided a unique opportunity to estimate age-specific incidence rates of ev71 infections.201222348156
development of a transcription-reverse transcription concerted reaction method for specific detection of human enterovirus 71 from clinical specimens.a transcription-reverse transcription (rt) concerted reaction (trcr) method was developed for rapid and specific detection of ev71 from clinical specimens. this method was validated with ev71 strains from all of the known genotypes (genotypes a, b1 to b5, and c1 to c5), with detection limits of 10 to 10(3) copies, and was useful for identification of ev71 from throat swabs of patients with hand, foot, and mouth disease (hfmd).201222357494
identification of a c2 subgenogroup strain of enterovirus 71 in a retrospective study in shandong province, china, from 1990 to 2010. 201222357503
[virologic and epidemiological characteristics of non-polio infection in croatia over a ten-year period (2000-2009)].the aim of the present study was to show the virologic and epidemiological characteristics of non-polio enterovirus (npev) infection over a ten-year period in croatia.201122359891
characterization and specificity of the linear epitope of the enterovirus 71 vp2 protein.enterovirus 71 (ev71) has emerged as a major causative agent of hand, foot and mouth disease in the asia-pacific region over the last decade. hand, foot and mouth disease can be caused by different etiological agents from the enterovirus family, mainly ev71 and coxsackieviruses, which are genetically closely related. nevertheless, infection with ev71 may occasionally lead to high fever, neurologic complications and the emergence of a rapidly fatal syndrome of pulmonary edema associated with brai ...201222361222
scavenger receptor b2 as a receptor for hand, foot, and mouth disease and severe neurological diseases.enterovirus 71 (ev71) is one of the major causative agents of hand, foot, and mouth disease (hfmd). infection with ev71 is occasionally associated with severe neurological diseases such as acute encephalitis, acute flaccid paralysis, and cardiopulmonary failure. because cellular receptors for viruses play an important role in cell, tissue, and species tropism, it is important to identify and characterize the receptor molecule. recently, cellular receptors and host factors that stimulate ev71 inf ...201222363322
a flavobacterium lindanitolerans strain isolated from the ascites sample of a chinese patient with ev71 virus infection.a strain of flavobacterium lindanitolerans isolated from a sick child's ascites was described. the 16s rrna gene of the strain was 100% identical to that of flavobacterium lindanitolerans which was first identified in india in 2008. it was first described that the isolate required x factor (hemin) for growth in the optimal conditions of 37 °c with 5% co(2). the isolate produced indole and h(2)s. it did not present hemolytic feature on blood agar.201122365408
crystal structure of human enterovirus 71.enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. here, we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the "pocket factor," a small molecule that stabilizes the virus, is partly exposed on the floor of the "canyon." thus, the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.201222383808
a sensor-adaptor mechanism for enterovirus uncoating from structures of ev71.enterovirus 71 (ev71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. no vaccine or antiviral therapy is available. high-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. in contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in ato ...201222388738
simultaneous determination of human enterovirus 71 and coxsackievirus b3 by dual-color quantum dots and homogeneous immunoassay.human enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have high risks for morbidity and mortality. a virus quantitation immunoassay has been proposed by employing two colored quantum dots (qds), antibodies of the virus, and graphene oxide (go). the qds are streptavidin-conjugated quantum dots (sa-qds), and the antibodies are biotinylated antibodies. biotinylated ev71 antibody (ab1) was associated with 525 nm green colored sa-qds via biotin-streptavidin interaction forming qds-ab1, whereas bio ...201222390751
[studies on anti-ev71 virus activity of traditional chinese medicine and its clinical application in treatment of hfmd].hand-foot-and-mouth disease is caused by intestinal virus infection. the viruses coxsackie a16 (ca16) and enterovirus 71 (ev71) are the main pathogens. between them, the virus ev71 is more dangerous and easier to cause serious complications, which leads to death or disability. currently, there are no effective antiviral drugs to treat ev71 infection. therefore, developing an effective drug against ev71 virus activity is significant. it has a huge potency of screening the anti-ev71 components and ...201122393752
outbreak of hand, foot and mouth disease/herpangina associated with coxsackievirus a6 and a10 infections in 2010, france: a large citywide, prospective observational study.hand, foot and mouth disease (hfmd) and herpangina (ha) are frequently caused by several distinct serotypes belonging to the human enterovirus a species (heva). enterovirus 71 is considered as a significant public health threat because of rare but fatal neurological complications. a sentinel surveillance system involving paediatricians from clermont-ferrand (france) was set up to determine the clinical and epidemiological characteristics of hfmd/ha associated with enterovirus infections. a stand ...201222404077
a reverse genetic study of the adaptation of human enterovirus 71 to growth in chinese hamster ovary cell cultures.we selected chinese hamster ovary (cho) cell-adapted strains of human enterovirus 71 (hev71) belonging to sub-genogroups b5 (hev71-b5) and c2 (hev71-c2) by serial passage in cho cells at a high multiplicity of infection. during the course of cho cell passage, virus growth improved significantly, with increasing virus titres and the presence of cytopathic effect observed. a study of virus growth kinetics revealed that the cho cell-adapted strains of hev71-b5 (cho-b5) and hev71-c2 (cho-c2) grew ef ...201222406130
bilirubin: an endogenous molecule with antiviral activity in vitro.bilirubin-ix-alpha (br) is the final product of heme metabolism through the heme oxygenase/biliverdin reductase (ho/bvr) system. previous papers reported on the microbicidal effects of the ho by-products biliverdin-ix-alpha, carbon monoxide and iron, through either direct or indirect mechanisms. in this paper the evidence of a virucidal effect of br against human herpes simplex virus type 1 (hsv-1) and the enterovirus ev71 was provided. bilirubin-ix-alpha, at concentrations 1-10 μm, close to tho ...201222408623
safety and immunogenicity of a novel human enterovirus 71 (ev71) vaccine: a randomized, placebo-controlled, double-blind, phase i clinical trial.there is an urgent need for a novel vaccine that is effective against human enterovirus 71 (ev71) outbreaks. a double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human ev71 vaccine in healthy adults, children and infants. the vaccine dosages were 200 u and 400 u for children and adults, and 100 u, 200 u and 400 u for infants. subjects were randomized to receive different dosages of the vaccine or placebo. adults received intramuscular injection on days 0 ...201222426327
increased frequency of th17 cells in the peripheral blood of children infected with enterovirus 71.enterovirus 71 (ev71) affects the health of young children globally causing severe neurologic diseases. the relationship between ev71 infection and t helper type 17 (th17) has not been described, although this new th subset or interleukin-17 (il-17) has been reported to be associated with other viral infections. the purpose of the current study was to describe the immune profile involving th17 cells, neutrophils, and related factors and to speculate on the possible immunopathogenesis of ev71 inf ...201222431024
[epidemiologic characteristics of hand-foot-mouth disease in guiyang between 2008 and 2010].to study the epidemiologic characteristics of hand-foot-mouth disease (hfmd) in guiyang between 2008 and 2010.201222433407
human scarb2-dependent infection by coxsackievirus a7, a14, and a16 and enterovirus 71.human enterovirus species a (hev-a) consists of at least 16 members of different serotypes that are known to be the causative agents of hand, foot, and mouth disease (hfmd), herpangina, and other diseases, such as respiratory disease and polio-like flaccid paralysis. enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hfmd. cva5, cva6, cva10, and cva12 mainly cause herpangina or are occasionally involved with sporadic cases of hfmd. we have previously shown tha ...201222438546
viral and host factors that contribute to pathogenicity of enterovirus 71.the single-stranded rna virus enterovirus 71 (ev71), which belongs to the picornaviridae family, has caused epidemics worldwide, particularly in the asia-pacific region. most ev71 infections result in mild clinical symptoms, including herpangina and hand, foot and mouth disease. however, serious pathological complications have also been reported, especially for young children. the mechanisms of ev71 disease progression remain unclear. the pathogenesis of adverse clinical outcomes may relate to m ...201222439724
occurrence of hand-foot-and-mouth disease pathogens in domestic sewage and secondary effluent in xi'an, china.hand, foot and mouth disease (hfmd), caused by a group of enteric viruses such as enterovirus 71 (ev71), coxsackievirus a16 (cva16) and coxsackievirus a10 (cva10), is heavily epidemic in east asia. this research focused on investigating the occurrence of hfmd pathogens in domestic sewage and secondary effluent before disinfection in a wastewater treatment plant (wwtp) in xi'an, the largest megacity in northwest china. in order to simultaneously detect all three hfmd pathogens, a semi-nested rt-p ...201222446307
expression and immunogenicity of novel subunit enterovirus 71 vp1 antigens.hand, foot, and mouth disease (hfmd) is a common viral illness in young children. hfmd is caused by viruses belonging to the enterovirus genus of the picornavirus family. recently, enterovirus 71 (ev71) has emerged as a virulent agent for hfmd with severe clinical outcomes. in the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit vp1 antigen for the design of ev71 vaccines. dna immunization was adopted as a simple technical ap ...201222450314
fisetin and rutin as 3c protease inhibitors of enterovirus a71.enterovirus a71 (ev-a71) causes severe complications: encephalitis, pulmonary edema, and death. no effective drug has been approved for clinical use. this study investigated the antiviral effects of flavonoids against ev-a71. an in vitro inhibitor screening assay using recombinant ev-a71 3c protease (3cpro) demonstrated fisetin and rutin inhibiting 3cpro enzymatic activity in a dose-dependent manner. cell-based fluorescence resonance energy transfer (fret) assay with an ev-a71 3cpro cleavage mot ...201222465253
inhibition of enterovirus 71 entry by transcription factor xbp1.inositol-requiring enzyme 1 (ire1) plays an important role in the endoplasmic reticulum (er), or unfolded protein, stress response by activating its downstream transcription factor x-box-binding protein 1 (xbp1). we demonstrated previously that enterovirus 71 (ev71) upregulated xbp1 mrna levels but did not activate spliced xbp1 (xbp1s) mrna or its downstream target genes, edem and chaperones. in this study, we investigated further this regulatory mechanism and found that ire1 was phosphorylated ...201222469468
cellular receptors for human enterovirus species a.human enterovirus species a (hev-a) is one of the four species of hev in the genus enterovirus in the family picornaviridae. among hev-a, coxsackievirus a16 (cva16) and enterovirus 71 (ev71) are the major causative agents of hand, foot, and mouth disease (hfmd). some other types of hev-a are commonly associated with herpangina. although hfmd and herpangina due to hev-a are common febrile diseases among infants and children, ev71 can cause various neurological diseases, such as aseptic meningitis ...201222470371
a 3d framework for understanding enterovirus 71.two papers report the structure of the virion of emerging pathogen ev71, providing a three-dimensional context for understanding many of its biological functions.201222472617
characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern china.human enterovirus 71 (ev71)-associated hand, foot, and mouth disease (hfmd) has been a leading cause of childhood infection in china since 2008. epidemic and molecular characteristics of hfmd have been examined in many areas of china, including the central and southern regions. however, clinical and genetic characterization of ev71 in the northeastern region of china is scarce. in this study, a series of analyses were performed on seven full-length ev71 sequences from hfmd patients who had eithe ...201222479324
recent advances in the molecular epidemiology and control of human enterovirus 71 infection.human enterovirus 71 (hev71) has emerged as an important cause of viral encephalitis in the southeast asia over the past 15 years. a pattern of increased epidemic activity and endemic circulation of hev71 has been observed since 1997 and is associated with the regular emergence of new genetic lineages. although the reason for this increase in hev71 circulation remains unknown, evidence is accumulating that recombination events may drive the evolution of new genetic lineages. prevention of hev71 ...201222482716
encephalitis due to emerging viruses: cns innate immunity and potential therapeutic targets.the emerging viruses represent a group of pathogens that are intimately connected to a diverse range of animal vectors. the recent escalation of air travel climate change and urbanization has meant humans will have increased risk of contacting these pathogens resulting in serious cns infections. many rna viruses enter the cns by evading the bbb due to axonal transport from the periphery. the systemic adaptive and cns innate immune systems express pattern recognition receptors prr (tlrs, rig-1 an ...201222484271
extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis: long-term neurologic follow-up.enterovirus 71 rhombencephalomyelitis with cardiopulmonary dysfunction has become an endemic problem in taiwan since an epidemic outbreak in 1998. such cases frequently involve significant morbidity and mortality. from october 2000-june 2008, we collected 10 consecutive patients diagnosed with enterovirus 71 rhombencephalomyelitis complicated by left heart failure, with or without pulmonary edema, and surviving more than 3 months after receiving extracorporeal life support. follow-up neurologic ...201222490767
simultaneous detection of enterovirus 71 and coxsackievirus a16 using dual-colour upconversion luminescent nanoparticles as labels.we highlight a novel fluorescence analysis for sensitive and selective detection of ev-71 and cv-a16 by combining labelling technology based on dual-colour upconversion fluorescence nanoparticles (ucnps) with magnetic bioseparation and concentration technology based on magnetite nanoparticles (mnps).201222498910
genetic characterization of enterovirus 71 isolated from patients with severe disease by comparative analysis of complete genomes.enterovirus 71 (ev71) which causes mild illness in children is also associated with severe neurological complications. this study analyzed the complete genomes of ev71 strains derived from mild and severe diseases in order to determine whether the differences of ev71 genomes were responsible for different clinical presentations. compared to complete genomes of ev71 strains derived from mild cases (less virulent strains), nucleotide differences in ev71 strains isolated from severe cases (more vir ...201222499017
[complete genome sequence characteristics of human enterovirus 71 strain isolated in yunnan, china].the complete nucleotide sequence of two human enterovirus 71 strains (kmm09 and km186-09) isolated in yunnan,china, were determined by rt-pcr and sequencing. as with other human enteroviruses, the genomes were 7 409 nucleotides (nts) in length and encoded 2 193 aa. phylogenetic analysis based on vp1 regions revealed that the two isolates belonged to subgenotype c4a. in structural genomic regions, subgenotype c4 was most homologous to other strains of c genotype when compared to other genotypes. ...201222519170
a case-control study of risk factors for severe hand-foot-mouth disease among children in ningbo, china, 2010-2011.a small fraction of hand-foot-mouth disease (hfmd) progression from the onset of severity to fatality may be remarkably rapid. early recognition of children at risk of severity is critical to increase treatment effectiveness and reduce acute mortality.201222527564
pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia and now is being recognized as an important neurotropic virus. effective medications and prophylactic vaccine against ev71 infection are urgently needed. based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated ev71 vaccine candidate has been developed and currently in human phase 1 clinical trial.201222529942
inhibition of enterovirus 71 (ev-71) infections by a novel antiviral peptide derived from ev-71 capsid protein vp1.enterovirus 71 (ev-71) is the main causative agent of hand, foot and mouth disease (hfmd). in recent years, ev-71 infections were reported to cause high fatalities and severe neurological complications in asia. currently, no effective antiviral or vaccine is available to treat or prevent ev-71 infection. in this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of ev-71. ninety five synthetic peptides (15-mers) overlapping the entire e ...201222563456
[survey on the recessive infection of pathogen to hand-foot-mouth disease among healthy adults and children in guangdong province].to understand the pathogen-carrying status of hand-foot-mouth disease (hfmd) among healthy people in guangdong province.201222575141
mouse adaptation of a sub-genogroup b5 strain of human enterovirus 71 is associated with a novel lysine to glutamic acid substitution at position 244 in protein vp1.most human enterovirus 71 (hev71) strains infect only primates and are unable to cause clinically apparent infection in mice. here we describe a mouse-adapted hev71 strain that belongs to sub-genogroup b5 with increased virulence in newborn balb/c mice. the mouse-virulent strain was initially selected by serial passage of a hev71 clinical isolate (hev71-b5) in chinese hamster ovary (cho) cells (cho-b5), followed by serial passage in newborn mice. virus from the fifth mouse passage was cultured t ...201222575826
paroxysmal supraventricular tachycardia in an infant with hand, foot, and mouth disease.an 11-month-old male infant was admitted to our hospital with fever, fussiness, poor feeding, vomiting, and tachypnea for two days prior. physical examination revealed sporadic papules and vesicles occurring on his hands, feet, face, and perianal mucosa. enterovirus 71 was identified from both throat swab and vesicle fluid using virus isolation techniques. the patient's heart rate fluctuated in a very narrow range from 180~210/beats/min regardless of his physiologic state. an electrocardiogram s ...201222577272
analysis of the th1/th2 reaction in the immune response induced by ev71 inactivated vaccine in neonatal rhesus monkeys.although clinical trials for the enterovirus type 71 (ev71) inactivated vaccine have been progressing, the potential mechanism of ev71 infection and its associated pathogenesis are not well-characterized in terms of comprehensive analysis of the induced immune response, which is generally recognized as an important indicator of the safety of vaccines. to investigate the th1/th2 response following viral challenge in neonatal rhesus monkeys immunized with different doses of ev71 inactivated vaccin ...201222585051
molecular epidemiology and evolution of human enterovirus serotype 68 in thailand, 2006-2011.publications worldwide have reported on the re-occurrence of human enterovirus 68 (ev68), a rarely detected pathogen usually causing respiratory illness. however, epidemiological data regarding this virus in particular on the asian continent has so far been limited.201222586446
linear normalised hash function for clustering gene sequences and identifying reference sequences from multiple sequence alignments.comparative genomics has put additional demands on the assessment of similarity between sequences and their clustering as means for classification. however, defining the optimal number of clusters, cluster density and boundaries for sets of potentially related sequences of genes with variable degrees of polymorphism remains a significant challenge. the aim of this study was to develop a method that would identify the cluster centroids and the optimal number of clusters for a given sensitivity le ...201222587938
daphne genkwa sieb. et zucc. water-soluble extracts act on enterovirus 71 by inhibiting viral entry.dried flowers of daphne genkwa sieb. et zucc. (thymelaeaceae) are a chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. however, the activity of this medicine against enteroviral infections has not been investigated. the water-extract of dried buds of d. genkwa sieb. et zucc. (dgfw) was examined against various strains of enterovirus 71 (ev71) by neutralization assay, and its initial mode of action was characterized by time-of-addition assa ...201222590685
clinical characteristics of hand, foot and mouth disease in harbin and the prediction of severe cases.hand, foot and mouth disease (hfmd) is an emerging public health problem in china, not only threatening the health of children, but also causing tremendous loss and burden to both families and society. the aim of this study was to characterize the epidemiology and clinical features of hfmd, and to understand the key factors affecting hfmd in the harbin region to provide scientific evidence for effective prevention and control strategies.201222613598
[distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].to explore the mechanism that how human enterovirus 71 (ev71) invades the brainstem and how intercellular adhesion molecules-1 (icam-1) participates by analyzing the expression and distribution of human ev71, and icam-1 in brainstem of infants with brain stem encephalitis.201222619799
tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in chinese healthy adults and children: an open label, phase 1 clinical trial.in this open labeled phase 1 clinical trial with enterovirus 71 (ev71) vaccine (clinicaltrials.gov number: nct01267903) performed in donghai county, jiangsu province, china, in january 2011. a total of 100 healthy participants, stratified by age (40 adults aged 16-22 y and 60 children aged 6-15 y), were enrolled from volunteers and sequentially received ev71 vaccines of 160u (only for children), 320u, or 640u on day 0 and 28, in a manner of dose escalation. all the participants were followed for ...201222634437
the pathogenesis and prevention of encephalitis due to human enterovirus 71.human enterovirus 71 (hev71) has emerged as a major cause of viral encephalitis in southeast asia, with increased epidemic activity observed since 1997. this is reflected in a large increase in scientific publications relating directly to hev71. new research is elucidating details of the viral life cycle, confirming similarities between hev71 and other enteroviruses. scavenger receptor b2 (scarb2) is a receptor for hev71, although other receptors are likely to be identified. currently, the only ...201222639066
[outbreak of acute enterovirus intestinal infection in sakhalin region in august 2010].the investigation of cases of acute intestinal infections in the sakhalin region of russia in august, 2010 is described. epidemiological and molecular biological studies were conducted. after initial pcr screening and determining the nucleotide sequences of the positive samples the following enteroviruses were found: coxsackie a2 - 42 samples (45%), coxsackie a4--31 sample (34%), enterovirus 71--6 samples (6,5%), coxsackievirus b5--6 samples (6,5%), coxsackie b3--4 samples (4%) and coxsackie b1- ...201222642180
prevention of human enterovirus 71 infection by kappa carrageenan.enterovirus 71 (ev 71), the newest member of enteroviridae, is notorious for its etiological role in epidemics of the hand-foot-and-mouth disease, particularly in association with fatal neurological complications in young children. searching for new and more effective agents against ev 71 infections has never relented as corresponding vaccines or antiviral drugs remain unavailable. sulfated polysaccharides from seaweed are known to possess a broad range of biological activities across anti-virus ...201222643729
a single mutation in capsid protein vp1 (q145e) of a genogroup c4 strain of human enterovirus 71 generates a mouse-virulent phenotype.we modified the capsid protein of a human enterovirus 71 (hev71) belonging to subgenogroup c4 (hev71-c4) to generate a mouse virulent strain, based on the genetic information derived from our previous subgenogroup b3 mouse-adapted virus. infectious clone-derived mutant virus populations containing the capsid protein mutations vp1-q145e and vp1-q145g were generated by site-directed mutagenesis of an infectious clone of a subgenogroup c4 strain. viruses expressing the vp1-q145e were virulent in 5- ...201222647370
antigenic characteristics of the complete and truncated capsid protein vp1 of enterovirus 71.the complete vp1 protein of enterovirus 71 (ev71) and a series of truncations were expressed in escherichia coli and their antigenic characteristics were studied. immunoblot analysis showed the major immunoreactive region of the vp1 protein was located in the n-terminal portion at position of amino acid (aa) 1-100. the complete vp1 possessed strong cross-reactivity with antisera against coxsackievirus a16 (ca16) and echovirus 6 (echo6), while the truncated fragment at position 1-100 aa only had ...201222659489
copi is required for enterovirus 71 replication.enterovirus 71 (ev71), a member of the picornaviridae family, is found in asian countries where it causes a wide range of human diseases. no effective therapy is available for the treatment of these infections. picornaviruses undergo rna replication in association with membranes of infected cells. copi and copii have been shown to be involved in the formation of picornavirus-induced vesicles. replication of several picornaviruses, including poliovirus and echovirus 11 (ev11), is dependent on cop ...201222662263
antiviral ability of kalanchoe gracilis leaf extract against enterovirus 71 and coxsackievirus a16.pandemic infection or reemergence of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. however, effective therapeutic drugs against ev71 and cva16 are rare. kalanchoe gracilis (l.) dc is used for the treatment of injuries, pain, and inflammation. this study investigated antiviral effects of k. gracilis leaf extr ...201222666293
induction of protective immune responses against ev71 in mice by baculovirus encoding a novel expression cassette for capsid protein vp1.ev71 is a major causative agent of hand, foot and mouth disease (hfmd) and is responsible for large outbreaks in various asian pacific countries. in the present study, we generated the recombinant baculovirus (bac-vp1) encoding vp1 in a novel expression cassette. the transmembrane domain of hemagglutinin of the h3n2 influenza virus was included in the cassette as a minimal membrane anchor for vp1. the protective immunity of bac-vp1 was investigated in a mouse model. the results showed that mice ...201222691220
[morphological changes of brain choroid plexuses and ventricle induced by enterovirus infections in monkeys].the morphological study of monkeys' brains, infected by the bulgaria strain of enterovirus-71 (ev71), revealed specific for truncus cerebral encephalomyelitis, reactive and destructive changes in different areas of the brainstem and the spinal cord. for the first time viral cytopathology and destruction of choroid plexuses as an important secretory organ of the central nervous system, and ventricle of the brain infected by enterovirus have been studied. the specificity of this infection and the ...201222712308
display of enterovirus 71 vp1 on baculovirus as a type ii transmembrane protein elicits protective b and t cell responses in immunized mice.human enterovirus 71 (ev71) has become a major public health threat across asia pacific. the virus causes hand, foot, and mouth disease which can lead to neurological complications in young children. there are no specific antivirals or vaccines against ev71 infection. the major neutralizing epitope of ev71 is located in the carboxy-terminal half of the vp1 protein at amino acid positions 215-219 (lim et al., 2012). to study the immunogenicity of vp1 we have developed a baculovirus vector which d ...201222728446
continuous veno-venous hemofiltration for treatment of enterovirus 71-induced fulminant cardiopulmonary failure: a case report.fulminant cardiopulmonary failure is a severe complication of hand, foot and mouth diseases due to enterovirus 71 infection, with a high mortality rate. the treatment is mainly supportive with aggressive cardiopulmonary resuscitation. we report the use of continuous veno-venous hemofiltration in a patient with pulmonary edema and shock due to enterovirus 71 infection. to the best of our knowledge, this is the first report of the use of continuous veno-venous hemofiltration to successfully treat ...201222734721
[chest x-ray findings in children with enterovirus 71 infection].to study the characteristics of the chest x-ray images in children infected with enterovirus 71.201222738450
[expression and activity analysis of enterovirus 71 3c protease in escherichia coli].the recombinant plasmid carrying the gene encoding 3c protease of enterovirus 71 (ev71) was constructed, the recombinant protein was then expressed and purified, the functional activity was also measured. firstly, the 3c protease gene was inserted into pet28a vector, the constructed recombinant plasmid was transformed into e. coli bl21 (de3) for expression under the induction of iptg. the expressed protein was purified by affinity chromatography (ni-nta) and the n-terminus his-tag was cleaved by ...201222764519
[the assemblage, purification and characterization of ev71 vlps expressed in baculovirus].to construct a recombinant expression plasmid bacmid-p1-3cd containing the p1 and 3cd genes of enterovirus 71(ev71), the p1 and 3cd genes were cloned into the same baculovirus shuttle vector (bacmid). recombinant acmnpv-p1-3cd was obtained by transfecting the bacmid-p1-3cd into the insect cell line of s f9. with the ifa and western-blot methods for identification of expression products confirmed that the target protein was expressed in interior of infected s f9 cells. electron microscopy showed ...201222764520
in vitro evaluation of the antiviral activity of heparan sulfate mimetic compounds against enterovirus 71.enterovirus 71 (ev71) is the causative agent of hand foot and mouth disease (hfmd) and can also cause fatal neurological complications for which currently there is no vaccine or approved antiviral drug. despite suggestions that heparan sulfate (hs)-like compounds are effective antivirals against various viruses, no research has been undertaken to examine their effects upon ev71. therefore, this study aimed to investigate the in vitro anti-ev71 effect of hs mimetics (heparin, heparan sulfate, and ...201222771616
development of murine monoclonal antibodies with potent neutralization effects on enterovirus 71.enterovirus 71 (ev71) is a member of the picornaviridae family and one of the main causative agents of hand, foot, and mouth disease (hfmd). currently, ev71 infection is prevalent in the asia-pacific regions where it affects millions of children under the age of five, causing significant morbidity and mortality. no specific vaccine or antiviral drugs are available for ev71. the development of murine monoclonal antibodies (mabs) with potent neutralization effects on ev71 is described. mab-secreti ...201222771741
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