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molecular diagnosis and clinical presentations of enteroviral infections in taipei during the 2008 epidemic.in 2008, an epidemic of enterovirus (ev) infection caused hand, foot, and mouth disease (hfmd) and herpangina in children in taiwan, and some of them died. to establish an early detection and effective management for children with ev71 infection, sensitive molecular diagnostic methods were applied from may to july 2008.201121524611
clinical and virological features of enterovirus 71 infections in denmark, 2005 to 2008.abstract background: since the late 1990s enterovirus 71 (ev71) has caused epidemics of hand, foot and mouth disease with fatal cases especially in the asian pacific region. the objective of this study was to describe the clinical and virological features of ev71 infections in denmark. methods: all enterovirus-positive samples in denmark are submitted to the national poliovirus laboratory for typing, and the ev71-positive samples are characterized by sequencing and phylogenetic analysis. clinica ...201121526904
synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir.background. enterovirus 71 (ev71) can cause severe diseases and even lead to death in children. there is no vaccine or specific antiviral therapy to prevent or cure ev71 infection. although interferon (ifn)-α has been used in the treatment of several viral infections, we found that ifn-α alone was ineffective in restricting ev71 replication in vero cells. methods. through a bioinformatics analysis, several cellular proteins in the ifn response pathway were identified as susceptible substrates th ...201121536800
formalin-inactivated vaccine provokes cross-protective immunity in a mouse model of human enterovirus 71 infection.human enterovirus 71 (hev71) has emerged as a major cause of epidemics of hand, foot and mouth disease associated with severe neurological sequelae in the asia-pacific region. in this study, a passive protection mouse model was used to evaluate the protective efficacy of formalin-inactivated hev71 vaccines derived from a chinese c4 genotype strain. pregnant mice were immunised using a prime/boost strategy and ≥50u of vaccine protected five-day-old pups from lethal challenge with a mouse-adapted ...201121550375
pathogenesis study of enterovirus 71 infection in rhesus monkeys.enterovirus 71 (ev71), a major pathogen that is responsible for causing hand-foot-and-mouth disease (hfmd) worldwide, is a member of the human enterovirus species a, family picornaviridae. hfmd that is caused by ev71 is usually characterized by vesicular lesions on the skin and oral mucosa and high morbidity rates in children; additionally, occasional fatal cases have been reported involving brainstem encephalitis and myelitis associated with cardiopulmonary collapse. although viral pathogenesis ...201121555996
[expression of vp0 protein of enterovirus 71 in escherichia coli and generation of the corresponding polyclonal antibodies in guinea pigs.]aim: to obtain recombinant vp0 protein of enterovirus 71, and generate the corresponding vp0-specific polyclonal antibodies, for molecular detection and characterization of ev71. methods: the vp0 gene was amplified by pcr and cloned into vector pet26b to make pet-vp0 for the prokaryotic expression of vp0. the recombinant vp0 protein was expressed in e.coli bl21 harboring pet-vp0, purified from inclusion bodies, renatured, and subsequently used to immunize guinea pigs. the resultant antisera were ...201121557912
inactivation of human enterovirus 71 and coxsackie virus a16 and hand, foot, and mouth disease.human enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the two major etiological agents in major outbreaks of hand, foot, and mouth disease. transmission of these viruses is facilitated by prolonged environmental survival and their resistance to biocides, and effective disinfection is crucial to interrupt the cycle of environmental spread. we tested the virucidal efficacy of sodium hypochlorite against both ev71 and cva16, performed according to the association of official analytical che ...201121565426
[molecular epidemiology of human enterovirus 71 strains in qingdao region, shandong province, 2007 - 2009.]objective: to study the molecular epidemiology of human enterovirus 71 (ev71) isolated from patients with hand-foot-mouth disease (hfmd) in qingdao region between 2007 and 2009. methods: throat swabs of hfmd were detected for total enterovirus (ev), ev71 and ca16 by fluorescence reverse transcription-polymerase chain reaction (rt-pcr). the vp1 region was amplified from positive ev71 specimens and 51 nucleotide sequences of vp1 gene were successfully sequenced. ev71 genotypes were characterized b ...201121569671
cross-reactivity of anti-ev71 igm and neutralizing antibody in series sera of patients infected with enterovirus 71 and coxsackievirus a 16.objectives: to evaluate the cross-reactivity of anti-ev71 igm and neutralizing antibody in series sera of patients infected with ev71 and ca16. methods: real-time rt-pcr, virus isolation, elisa and neutralization test were used to detect enteroviruses from clinical specimens and series sera of 79 hfmd patients. results: 27 ev71, 37 ca16, and 11 other enterovirus-infected patients were identified by rt-pcr. among ev71 infected patients, anti-ev71 igm positive ratios were 87.5% during 1-3 days aft ...201121574094
purification and characterization of enterovirus 71 viral particles produced from vero cells grown in a serum-free microcarrier bioreactor system.enterovirus 71 (ev71) infections manifest most commonly as a childhood exanthema known as hand-foot-and-mouth disease (hfmd) and can cause neurological disease during acute infection.201121603631
a mouse muscle-adapted enterovirus 71 strain with increased virulence in mice.enterovirus 71 (ev71) infections can usually cause epidemic hand, foot, and mouth disease (hfmd), and occasionally lead to aseptic meningitis, encephalitis, and polio-like illness. skeletal muscles have been thought to be crucial for the pathogenesis of ev71-related diseases. however, little is known about the virulence of mouse muscle-adapted ev71. the ev71 0805 were subjected to four passages in the mouse muscle to generate a mouse-adapted ev71 strain of 0805a. in comparison with the parental ...201121612764
comparative proteome analyses of host protein expression in response to enterovirus 71 and coxsackievirus a16 infections.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are the main etiological agents of hand, foot and mouth disease (hfmd), a common disease among children and had caused several outbreaks in the asia-pacific region. although being genetically close to each other, ev71 infection can cause serious and fatal neurological complications like encephalitis, myocarditis, acute flaccid paralysis (afp) and aseptic meningitis, but not in ca16 infections. in this study, the cellular response of host cells ...201121621020
visual detection of human enterovirus 71 subgenotype c4 and coxsackievirus a16 by reverse transcription loop-mediated isothermal amplification with the hydroxynaphthol blue dye.a sensitive reverse transcription loop-mediated isothermal amplification (rt-lamp) assay was developed for rapid visual detection of human enterovirus 71 subgenotype c4 (ev71-c4) and coxsackievirus a16 (cva16) infection, respectively. the reaction was performed in one step in a single tube at 65°c for 60min with the addition of the hydroxynaphthol blue (hnb) dye prior to amplification. the detection limits of the rt-lamp assay were 0.33 and 1.58 of a 50% tissue culture infective dose (tcid(50)) ...201121621554
[rt-pcr identification and genetic characterizations of vp1 region of human enterovirus 71 isolated in beijing in 2008].to study the genetic characterizations of vp1 region of human enterovirus 71 (hev71) isolated from clinical specimens of hand, foot and mouth disease (hfmd) patients in beijing in 2008.201021604564
[human enterovirus 71 that firstly isolated in qinghai province and their genetic features of vp1 region].to study the genetic characterizations of vp1 gene of human enterovirus 71 (hev71) isolated from clinical specimens of hand, foot and mouth disease (hfmd) patients in qinghai province in 2008.201021604569
in vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors.background: enterovirus type 71 (ev71) causes large outbreaks with significant mortality among young children, and no specific antiviral treatment is currently available. antibody-based therapy represents a promising alternative strategy for lethal ev71 infection. our previous data has shown that anti-ev71 neutralization antibodies were present in a significant proportion of blood donors in china. objectives: to produce a new human intravenous immunoglobulin (ivig) product containing high titer ...201121641277
the virology and developments toward control of human enterovirus 71.enterovirus 71 (ev71), a member of the enterovirus genus in the picornaviridae family, was first recognized as a dermotrophic virus that usually cause mild, self-limiting hand-foot-and-mouth disease (hfmd). however, ev71 infection can sometimes induce a variety of severe neurological complications and even death. current large outbreaks of ev71 make this virus being a major public health issue. intense effort has been made to address its underlying pathogenesis and to develop effective means for ...201121651436
epidemics of enterovirus infection in chungnam korea, 2008 and 2009.abstract: previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in chungnam, korea from 2005 to 2006. the present study extended these observations to 2008 and 2009. in this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. the most prevalent month was july: 42.9% in 2008 and 31.9% in 2009. the highest rate of enterovirus-positive samples occurred in children < 1-year- ...201121668960
crystal structures of enterovirus 71 3c protease complexed with rupintrivir reveal the roles of the catalytically important residues.ev71 is the primary pathogen causing hfmd, however, the effective antiviral drug is currently unavailable. rupintrivir, an inhibitor against hrv, has potent antiviral activities against ev71. we determined high-resolution crystal structures of ev71 3c(pro)/rupintrivir complex, showing that although rupintrivir interacts with ev71 3c(pro) similarly as with hrv 3c(pro), the c-terminal of the inhibitor cannot accommodate in the leaving group pockets of ev71 3c(pro). our structures reveal that ev71 ...201121813612
enterovirus 71 2c protein inhibits tnf-{alpha}-mediated activation of nf-{kappa}b by suppressing i{kappa}b kinase {beta} phosphorylation.enterovirus 71 (ev71), a single, positive-stranded rna virus, has been regarded as the most important neurotropic enterovirus after the eradication of the poliovirus. ev71 infection can cause hand, foot, and mouth disease or herpangina. cytokine storm with elevated levels of proinflammatory and inflammatory cytokines, including tnf-α, has been proposed to explain the pathogenesis of ev71-induced disease. tnf-α-mediated nf-κb signaling pathway plays a key role in inflammatory response. we hypothe ...201121810613
molecular detection and identification of enteroviruses in children admitted to a university hospital in greece.although enteroviral infections occur frequently during childhood, the circulation of particular serotypes has never been studied in greece. the objectives of the present report were molecular detection and identification of human enteroviruses in children admitted with nonspecific febrile illness or meningitis to a university hospital during a 22-month period. a one-step real-time rt-pcr protocol was used for rapid enterovirus detection in genetic material extracted directly from clinical sampl ...201121803150
circulating coxsackievirus a16 identified as recombinant type a human enterovirus, china.to determine the relationship of coxsackievirus a16 (ca16) to prototype ca16-g10, we conducted a phylogenetic analysis of circulating ca16 strains in china. complex recombinant forms of ca16-related viruses involving multiple human enteroviruses, subgroup a (ca4, ca16, and enterovirus 71), are prevalent among patients with hand, foot, and mouth disease.201121801645
enterovirus 71 and coxsackievirus a16 3c proteases: binding to rupintrivir and their substrate, and anti-hfmd drug design.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hand foot and mouth disease (hfmd) which is prevalent in asia. thus far there are no prophylactic or therapeutic measures against hfmd. the 3c proteases from ev71 and cva16 play important roles in viral replication and are therefore ideal drug targets. by using biochemical, mutational and structural approaches, we broadly characterized both proteases. a series of high-resolution structures of the free or subst ...201121795339
[the genetical evolution of the full length genes of 5 ev 71 strains from 5 shenzhen patients with hand-food-mouth disease associated with ev71 infection].to investigate the characteristics of molecular epidemiology and molecular evolution of 5 ev 71 (enterovirus 71, ev71) strains from 5 shenzhen patients with hand-food-mouth disease associated with ev 71 infection.201121789856
[enterovirus 71 induces apoptosis in a bax dependent manner].to explore the molecular mechanism of apoptosis induced by enterovirus 71 (ev71) infection.201121789855
sumoylation-promoted enterovirus 71 3c degradation correlates with a reduction in viral replication and cell apoptosis.enterovirus (ev) 71, a member of the picornaviridae family, may cause serious clinical manifestations associated with the central nervous system. enterovirus 3c protease is required for virus replication and can trigger host cell apoptosis via cleaving viral polyprotein precursor and cellular proteins, respectively. while the role of the 3c protease in processing viral and cellular proteins has been established, very little is known about the modulation of ev71 3c function by host cellular facto ...201121784861
[seroepidemiology investigation of neutralizing antibody against enterovirus 71 among healthy people in tianjin].to investigate the latent infection caused by enterovirus 71 (ev71) among healthy people in tianjin and to provide evidence on prevention and control hand-food and mouth diseases (hfmd).201121781473
[progress in research on enterovirus type 71]. 201121774260
[sequence and antigenicity analysis for vp4s of ev71 strains isolated from children in beijing].in order to learn about the correlation between the sequences of vp4 of ev71 and clinical symptoms of patients and analyze the antigenicity of vp4 of ev71, as well as the cross-reactivity with vp4 of ca16, the sequences of vp4 gene from 10 ev71 strains isolated from infants and children with hand, foot and mouth diseases (hfmd) during 2007 to 2009 were determined through standard molecular cloning protocols, and the results were analyzed by editseq and megalign of dnastar. full-length genes of v ...201121774244
development and evaluation of reverse transcription-loop-mediated isothermal amplification assay for rapid detection of enterovirus 71.abstract: background: hand, foot, and mouth disease (hfmd) caused by enterovirus 71 (ev71) is very common in china. it is difficult to distinguish between ev71 and coxsackievirus a16 (cva16) infections in clinical hfmd patients. routine laboratory diagnosis of ev71 infection is time-consuming and requires expensive instruments. in this study, we have developed a one-step, single tube, reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay for rapid and sensitive detection o ...201121767352
the seroprevalence and seroincidence of enterovirus71 infection in infants and children in ho chi minh city, viet nam.enterovirus 71 (ev71)-associated hand, foot and mouth disease has emerged as a serious public health problem in south east asia over the last decade. to better understand the prevalence of ev71 infection, we determined ev71 seroprevalence and seroincidence amongst healthy infants and children in ho chi minh city, viet nam. in a cohort of 200 newborns, 55% of cord blood samples contained ev71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. th ...201121765891
partial protection against enterovirus 71 (ev71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the ev71 vp1 fragment.enterovirus 71 (ev71) infection may cause severe neurological complications, particularly in young children. despite the risks, there are still no commercially available ev71 vaccines. hence, a candidate vaccine construct, containing recombinant newcastle disease virus capsids that display an ev71 vp1 fragment (npt-vp1(1-100) ) protein, was evaluated in a mouse model of ev71 infection. previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabb ...201121837796
neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications.enterovirus 71 (ev71) has emerged as a significant pathogen causing large outbreaks in china for the past 3 years. developing an ev71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to ev71 infection remains unclear. we examined the neutralizing antibody titers in hfmd patients and compared them to those of asymptomatic healthy children and young adults. we found that 80% of hfmd patients became positive for neutralizing antibodies ag ...201121679417
host factors in enterovirus 71 replication.enterovirus 71 (ev71) infections continue to remain an important public health problem around the world, especially in the asia-pacific region. there is a significant mortality rate following such infections, and there is neither any proven therapy nor a vaccine for ev71. this has spurred much fundamental research into the replication of the virus. in this review, we discuss recent work identifying host cell factors which regulate the synthesis of ev71 rna and proteins. three of these proteins, ...201121715481
cleavage of the adaptor protein trif by enterovirus 71 3c inhibits antiviral responses mediated by toll-like receptor 3.enterovirus 71 (ev71) causes hand-foot-and-mouth disease and neurological complications in young children. although the underlying mechanisms remain obscure, impaired or aberrant immunity is thought to play a role. in infected cells, ev71 suppresses type i interferon responses mediated by retinoid acid-inducible gene i (rig-i). this involves the ev71 3c protein, which disrupts the formation of a functional rig-i complex. in the present study, we report that ev71 inhibits the induction of innate ...201121697485
immunoprotection elicited by an enterovirus type 71 experimental inactivated vaccine in mice and rhesus monkeys.a number of commonly recognized public health issues are associated with ev71 infection, including the induction of severe cases of hand-foot-and-mouth disease (hfmd). because of such issues, research and development of ev71 vaccine candidates is of growing importance. in the present study, an experimental ev71 inactivated vaccine was prepared, and its corresponding immunogenicity was analyzed. the immune responses and immunoprotective effect induced by the vaccine in mice and rhesus monkeys are ...201121722686
evolution of re-emergent virus and its impact on enterovirus 71 epidemics.enterovirus 71 (ev71), a member of the enterovirus genus in the picornaviridae family, has become an emergent infectious disease worldwide, most notably in asia. as a neurotropic virus, ev71 infection occasionally causes neurological diseases with pulmonary edema, which is fatal for children. in this review, we examine the epidemiology of ev71, with three waves of increased ev71 activity since the 1970s and discuss the genotypic changes in phylogeny between the outbreaks or epidemics. genetic ch ...201121715436
dids blocks a chloride-dependent current that is mediated by the 2b protein of enterovirus 71. 201121747413
Development of a quantitative enzyme linked immunosorbent assay for monitoring the Enterovirus 71 vaccine manufacturing process.Enterovirus 71 (EV71), the etiologic agent causes outbreaks with significant mortality in young children in Asia and currently there is no vaccine available. In this study, we report a quantitative enzyme linked immunosorbent assay (Q-ELISA) to determine the concentration of the EV71 VP2 antigen. EV71 virus-like particles (VLPs) were produced in the baculovirus expression system and used as the EV71 antigen reference standard. Antisera from both EV71-immunized chickens and rabbits were very effi ...201121704080
hand foot and mouth disease due to enterovirus 71 in malaysia.hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. the illness is caused by a number of enteroviruses with coxsackievirus a16 and enterovirus 71 as the main causative agents. human enterovirus 71 (ev71) belongs to the species human enterovirus a under the genus enterovirus within the family picornaviridae. ev71 has ...201121847753
[Gene cloning and immunogenicity analysis of the structural proteins VP1-VP4 of enterovirus 71].To clone the genes encoding the structural proteins VP1-VP4 of enterovirus 71 and investigate the immunogenicity of the expressed recombinant proteins.201122126762
a single nucleotide in stem loop ii of 5'-untranslated region contributes to virulence of enterovirus 71 in mice.enterovirus 71 (ev71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the asia-pacific region while virulence determinant remains unexplored.201122069490
[Epidemiological features of hand, foot and mouth disease in China, 2008 - 2009].To clarify the seasonal and geographical difference and pathogen patterns so as to provide reference of prevention and control of the disease through analyzing the epidemical characteristics of reported hand-foot-mouth disease (HFMD) cases in China, 2008 - 2009.201121933538
inhibition of enterovirus 71 replication by chrysosplenetin and penduletin.in recent years, enterovirus 71 (ev71) infections have caused an increasing epidemic in young children, accompanying with more severe nervous system disease and more deaths. unfortunately, there is no specific medication for it so far. here we investigated the anti-ev71 activity of chrysosplenetin and penduletin, two o-methylated flavonols isolated from the leaves of laggera pterodonta. these two compounds were found to have strong activity in vitro against ev71 with low cytotoxicity. in the cyt ...201121914477
display of vp1 on the surface of baculovirus and its immunogenicity against heterologous human enterovirus 71 strains in mice.human enterovirus 71 (ev71) is a common cause of hand, foot and mouth disease (hfmd) in young children. it is often associated with severe neurological diseases and has caused high mortalities in recent outbreaks across the asia pacific region. currently, there is no effective vaccine and antiviral agents available against ev71 infections. vp1 is one of the major immunogenic capsid protein of ev71 and plays a crucial role in viral infection. antibodies against vp1 are important for virus neutral ...201121747954
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
hand, foot, and mouth disease in china: patterns of spread and transmissibility.there were large outbreaks of hand, foot, and mouth disease in both 2008 and 2009 in china.201121968769
[recent advances in human enterovirus 71 and host interactions]. 201121998965
reemerging of enterovirus 71 in taiwan: the age impact on disease severity.enterovirus 71 (ev71) infection commonly strike children under the age of 3 years, with an occasionally unfavorable outcome in children. this study was designed to explore the relationship between age and the severity of complications, which may associate with antibody-dependent enhancement (ade) in ev71. all ev71-infected patients during the outbreak of 2008 were recruited. in total, 134 patients were enrolled and categorized into two age groups, 0-12 months (n = 18) and >12 months (n = 116). p ...201121983920
Survey of enterovirus infections from hand, foot and mouth disease outbreak in china, 2009.ABSTRACT:201122054534
external quality assessment for enterovirus 71 and coxsackievirus a16 detection by reverse transcription-pcr using armored rna as a virus surrogate.three armored rnas (virus-like particles [vlps]) containing target sequences from enterovirus 71 (ev71) and coxsackievirus a16 (ca16) and a pan-enterovirus (pan-ev) sequence were constructed and used in an external quality assessment (eqa) to determine the performance of laboratories in the detection of ev71 and ca16. the eqa panel, which consisted of 20 samples, including 14 positive samples with different concentrations of ev and either ev71 or ca16 armored rnas, 2 samples with all 3 armored r ...201121865426
Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication.Human enterovirus 71 (EV71) infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE) on rhabdomyosarcoma (RD) cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that ...201122029605
simple and rapid detection of human enterovirus 71 by reverse-transcription and loop-mediated isothermal amplification: cryopreservation affected the detection ability.human enterovirus 71 (ev71) is the primary pathogen of hand, foot, and mouth disease (hfmd). ev71 infection may lead to neurologic damage, with higher incidence of fatality compared with other hfmd pathogens. an effective drug or vaccine against ev71 infection is currently unavailable. it is desirable to determine the pathogen of hfmd accurately and quickly for early treatment. in the current study, reverse-transcription and loop-mediated isothermal amplification (rt-lamp) technology were develo ...201121899976
[development of a gexp based multiplex rt-pcr assay for simultaneous differentiation of nine human hand food mouth disease pathogens].a multiplex rt-pcr assay based on gexp system was developed in order to detect simultaneously human enterovirus 71 (ev71) and coxsackievirus a16 (cva16) and other coxsackieviruses (cva4, 5, 9 and 10, cvb1, 3 and 5). enterovirus detection was performed with a mixture of 12 pairs of oligonucleotide primers including one pair of published primers for amplifying all known pan-enterovirus genomes and eleven primer pairs specific for detection of the vp1 genes of ev71, c a16, cva4, cva5, cva9, cva10, ...201121874901
molecular analysis of virulent determinants of enterovirus 71.enterovirus 71 (ev71) is the most important causative agent of hand, foot and mouth disease (hfmd) in children. in most cases, it is a self-limiting illness. however some ev71 infectious cases can develop severe clinical outcomes, such as encephalitis, meningitis, poliomyelitis like paralysis, and even death. to identify the determinants of virulence, the deduced amino acid sequence of polyprotein and nucleotide sequence of 5'-ntr and 3'-ntr in 25 sc-ev71 strains (strains from severe cases) and ...201122039449
Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance imaging findings.INTRODUCTION: Most enterovirus (EV) 71 infections manifest as mild cases of hand-foot-mouth disease (HFMD)/herpangina with seasonal variations, having peak incidence during the summer. Meanwhile, EV 71 may involve the central nervous system (CNS), causing severe neurologic disease. In many cases, enteroviral encephalomyelitis involves the central midbrain, posterior portion of the medulla oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral roots of the cervical spinal ...201121861081
Enterovirus 71 adsorption on metal ion-composite chitosan beads.In this study, we developed composite chitosan beads combining various metal ions, including Ni(2+) , Cu(2+) , Zn(2+) , and Fe(2+) , for direct adsorption of enterovirus 71 (EV71). The metal-ion species had significant effects on the adsorption capacity of beads. Among these metal ion-composite chitosan beads, Ni(2+) -chitosan beads exhibited the best adsorption capacity of EV71. Using a concentration of 0.01-M Ni(2+) was found to best provide for bead formation and EV71 adsorption. The adsorpti ...201121936063
Enterovirus 71 vaccine: when will it be available? 201121742245
[the establishment of real time fluorescent pcr detecting method and preliminary application on pathogenesis of hfmd].to establish the real-time fluorescent pcr method for detecting enterovirus, enterovirus 71 and coxsackievirus a 16 nucleic acid.201121863646
[genetic evolution of vp1 of enterovirus type 71 in shenzhen].genetic evolution of vp1 of enterovirus type 71 in shenzhen were analyzed.201121977583
antigenicity, animal protective effect and genetic characteristics of candidate vaccine strains of enterovirus 71.enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease. recently, several ev71 inactivated vaccine candidates have been development in mainland china. to compare the antigenicity and genetic characteristics of different candidate vaccine strains for ev71, the genomes of 11 ev71 strains were sequenced. the cross-protection capacities were determined by neutralizing antibody test and were further assessed in neonatal mice. the results showed 93.0%-99.8% genome h ...201121984267
effects of lactoferrin-containing formula in the prevention of enterovirus and rotavirus infection and impact on serum cytokine levels: a randomized trial.lactoferrin has been shown to exhibit anti-enterovirus 71 (ev71) and antirotavirus properties. this trial was conducted to determine whether a formula containing bovine lactoferrin (blf) exerts a protective effect against ev71 or rotavirus infection among children from 2 to 6 years old.201121880194
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
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
simultaneously typing nine serotypes of enteroviruses associated with hand, foot, and mouth disease by a gexp analyzer-based multiplex reverse transcription-pcr assay.hand, foot, and mouth disease (hfmd) is a contagious enteroviral disease occurring primarily in young children and caused by enterovirus 71 (ev71), coxsackievirus a16 (cva16), and other serotypes of coxsackievirus and echovirus. in this study, a gexp analyzer-based multiplex reverse transcription (rt)-pcr assay (gexp assay) consisting of chimeric primer-based pcr amplification with fluorescent labeling and capillary electrophoresis separation was developed to simultaneously identify nine serotyp ...201122116146
Emergence and transmission pathways of rapidly evolving evolutionary branch c4a strains of human enterovirus 71 in the central plain of china.Large-scale outbreaks of hand, foot, and mouth disease (HFMD) occurred repeatedly in the Central Plain of China (Shandong, Anhui, and Henan provinces) from 2007 until now. These epidemics have increased in size and severity each year and are a major public health concern in mainland China.201122125635
immunogenicity of a truncated enterovirus 71 vp1 protein fused to a newcastle disease virus nucleocapsid protein fragment in mice.enterovirus 71 (ev71) is one of the viruses that cause hand, foot and mouth disease. its viral capsid protein 1 (vp1), which contains many neutralization epitopes, is an ideal target for vaccine development. recently, we reported the induction of a strong immune response in rabbits to a truncated vp1 fragment (nt-vp1t) displayed on a recombinant newcastle disease virus (ndv) capsid protein. protective efficacy of this vaccine, however, can only be tested in mice, since all ev71 animal models thu ...201121978156
in vitro activity of paris polyphylla smith against enterovirus 71 and coxsackievirus b3 and its immune modulation.enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have resulted in severe pathogenesis caused by the host's immune response, including the cytokine cascade. paris polyphylla smith is a folk medicinal plant in asia traditionally prescribed for the reduction of pain and elimination of poisoning. in this study, we investigated the anti-ev71 and cvb3 activity of p. polyphylla smith as well as its immune modulation. the ic(50) for the p. polyphylla smith 95% ethanol extract against ev71 and cvb3 wer ...201122083992
comparing enterovirus 71 with coxsackievirus a16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of vp1s and vp4s.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are two major etiological agents of hand, foot and mouth disease (hfmd). ev71 is associated with severe cases but not ca16. the mechanisms contributed to the different pathogenesis of these two viruses are unknown. vp1 and vp4 are two major structural proteins of these viruses, and should be paid close attention to.201122050722
[study on the prevalence of acute flaccid paralysis and hand foot mouth disease in beijing 2006 - 2008].to study the prevalence of acute flaccid paralysis (afp) and hand foot mouth disease (hfmd) in beijing, from 2006 - 2008.201121933539
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
identification of bpr3p0128 as an inhibitor of cap-snatching activities of influenza virus.the aim of this study was to identify the antiviral mechanism of a novel compound, bpr3p0128. from a large-scale screening of a library of small compounds, bpr3p compounds were found to be potent inhibitors of influenza viral replication in madin-darby canine kidney (mdck) cells. bpr3p0128 exhibited inhibitory activity against both influenza a and b. the 50% inhibitory concentrations were in the range of 51-190 nm in mdck cells as measured by inhibition of cytopathic effect assays. bpr3p0128 app ...201121930871
[experts consensus on rescue and treatment of severe cases with enterovirus 71 (ev71) infection]. 201122176902
Mutations in VP2 and VP1 capsid proteins increase infectivity and mouse lethality of enterovirus 71 by virus binding and RNA accumulation enhancement.Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease. EV71 infection occasionally associates with severe neurological sequelae such as brainstem encephalitis or poliovirus-like paralysis. We demonstrated that mouse-adapted strain increases infectivity, resulting in higher cytotoxicity of neuron cells and mortality to neonatal mice than a non-adapted strain. Results pointed to EV71 capsid region determining viral infectivity and mouse lethality. Mutant virus with lysine to methio ...201222078110
circulation of multiple enterovirus serotypes causing hand, foot and mouth disease in india.hand, foot and mouth disease (hfmd), a common contagious disease that usually affects children, can be caused by enteroviruses. coxsackievirus a16 (cv-a16) and enterovirus (ev) 71(ev-71) are known to be the major etiological agents of hfmd. other ev serotypes- cv-a4-7, cv-a9-10, cv-b1-3, cv-b5, e-4 and e-19 have been also found associated with both sporadic infections and outbreaks of hfmd. in india, outbreaks of hfmd have been documented; however, molecular characterization of the etiological a ...201122052995
[evaluation of immune responses and related patho-inflammatory reactions of a candidate inactivated ev71 vaccine in neonatal monkeys].to evaluate the safety of enterovirus type 71 (ev71) inactivated vaccine (human diploid derived) for infection prevention in an animal model by investigating the immune responses and related patho-inflammatory reactions.201122093894
a non mouse-adapted enterovirus 71 (ev71) strain exhibits neurotropism causing neurological manifestations in a novel mouse model of ev71 infection.enterovirus 71 (ev71) is a neurotropic pathogen that has been consistently associated with the severe neurological forms of hand, foot and mouth disease. the lack of a relevant animal model has hampered our understanding of ev71 pathogenesis, in particular the route and mode of viral dissemination. it has also hindered the development of effective prophylactic and therapeutic approaches, making ev71 one of the most pressing public health concerns in southeast asia.here we report a novel mouse mo ...201122130542
viral kinetics of enterovirus 71 in human abdomyosarcoma cells.to characterise the viral kinetics of enterovirus 71 (ev71).201122039330
[construction and identification of a vector inserted with gene of t7 rna polymerase].to develop a system to rescue virus by intracellular expression of t7 rna polymerase.201121863644
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
exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice.neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human enterovirus 71 (ev71) strain mp4. however, the hallmark of severe human ev71 infection, pulmonary edema (pe), was not evident.201122054060
the persistent circulation of enterovirus 71 in people's republic of china: causing emerging nationwide epidemics since 2008.emerging epidemics of hand-foot-and-mouth disease (hfmd) associated with enterovirus 71 (ev71) has become a serious concern in mainland china. it caused 126 and 353 fatalities in 2008 and 2009, respectively. the epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. to understand the virological evolution of this emerging outbreak, 326 vp1 gene sequences of ev71 detected in china from 1987 to 2009 were collected fo ...201121980521
[autophagy inhibitor 3-ma decreases the production and release of infectious enterovirus 71 particles].to determine whether or not enterovirus 71 (enteroviurs 71, ev71) may induce autophagy and affect the production and release of ev71 after the treatment of autophagy inhibitor.201121977584
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
prevalence of antibodies against enterovirus 71 in children from lu'an city in central china.we performed preepidemic and postepidemic serologic surveys to elucidate the rate of enterovirus 71 (ev71) infection in lu'an city, anhui province, central china. for the preepidemic study, a total of 472 healthy infants and children (age range, neonates to 15 years) were randomly selected before the 2008 outbreak of ev71 in the region. blood samples were collected and tested for neutralizing antibodies (nabs) against ev71 by performing a microneutralization assay. the results of preepidemi ...201122116336
[etiology of hand, foot and mouth disease in qingdao during 2008-2009].an etiology study on hfmd in qingdao region during 2008-2009 was conducted. the virus rna were isolated from throat swabs of hfmd,the ev, ev71 and cva16 were detected by multiplex realtime rt-pcr. for those specimens with ev positive and both ev71 and cva16 negative,a reverese transcription-seminested polymerase chain reaction (rt-snpcr) was perfomed to amplify part sequence of the vp1 gene for sabsequent analysis to identify the serotype. the results indicated that ev71 and cva16 were the major ...201121998955
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
[Mechanism of intravenous immunoglobulin therapy for severe hand-foot-mouth disease: a review].Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by various enteroviruses. Recently, large HFMD outbreaks caused by enterovirus type 71 (EV71) have been frequently reported in China, posing great threats on children's health. There is no specific antiviral therapy for severe HFMD, and patient management mainly depends on supportive and symptomatic treatment. Intravenous immunoglobulin (IVIG) is a pharmaceutical preparation of human IgG that is pooled from thousands of healthy ...201121845837
Modification of the untranslated regions of human enterovirus 71 impairs growth in a cell-specific manner.Human enterovirus 71 (HEV71) is the causative agent of hand, foot, and mouth disease and associated acute neurological disease. At present, little is known about the genetic determinants of HEV71 neurovirulence. Studies of related enteroviruses have indicated that the untranslated regions (UTRs), which control virus-directed translation and replication, also exert significant influence on neurovirulence. We used an infectious cDNA clone of a subgenogroup B3 strain to construct and characterize c ...201222031931
far upstream element binding protein 1 binds the internal ribosomal entry site of enterovirus 71 and enhances viral translation and viral growth.enterovirus 71 (ev71) is associated with severe neurological disorders in children, and has been implicated as the infectious agent in several large-scale outbreaks with mortalities. upon infection, the viral rna is translated in a cap-independent manner to yield a large polyprotein precursor. this mechanism relies on the presence of an internal ribosome entry site (ires) element within the 5'-untranslated region. virus-host interactions in ev71-infected cells are crucial in assisting this proce ...201121880596
Dual-Color Fluorescence and Homogeneous Immunoassay for the Determination of Human Enterovirus 71.We have developed a new fluorescent immune ensemble probe comprised of a conjugated lower toxic water-soluble CdTe:Zn(2+) quantum dots (QDs) and Ru(bpy)(2)(mcbpy-O-Su-ester)(PF(6))(2)- antibody complex (Ru-Ab) for the dual-color determination of human enterovirus 71 (EV71) in homogeneous solution. EV71 monoantibody was easily covalently conjugated with Ru(bpy)(2)(mcbpy-O-Su-ester)(PF(6))(2) to form a stable complex Ru-Ab, which acted both as an effective quencher of QDs fluorescence and the capt ...201121838323
Synthesis, structure-activity relationship and in vitro biological evaluation of N-arylethyl isoquinoline derivatives as Coxsackievirus B3 inhibitors.Currently, there is no approved antiviral drug for the infection caused by enteroviruses. A series of novel N-arylethyl isoquinoline derivatives defined with substituents on the ring A and C were designed, synthesized and evaluated in vitro for their activities against Coxsackievirus B3 (CVB3). The primary structure-activity relationship revealed that substituents on the ring A were not beneficial for the activity. Among these analogs synthesized, compound 7f bearing a methylenedioxy at the R(4) ...201121880491
[Genomic characteristics and recombination of enterovirus 71 strains isolated in Henan Province between 2008 and 2010].To reveal the genetic features and recombination of enterovirus 71 isolates between 2008 and 2010. A total of 5 enterovirus 71 isolates were sequenced completely and phylogenetic analysis and recombination were performed. Phylogenetic analysis based on VP1 regions revealed that the Henan enterovirus 71 between 2008 and 2010 belonged to C4a in subgenotype C4. Bootscan analyses and phylogenetic analysis based on the 5'UTR, P1, P2, P3 genomic regions revealed the recombinations between EV71 genotyp ...201121998954
serum microrna expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease.altered circulating microrna (mirna) profiles have been noted in patients with microbial infections. we compared host serum mirna levels in patients with hand-foot-and-mouth disease (hfmd) caused by enterovirus 71 (ev71) and coxsackievirus 16 (cva16) as well as in other microbial infections and in healthy individuals. among 664 different mirnas analyzed using a mirna array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. expression levels of ten ...201122087245
The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore.Enterovirus 71 (EV71) has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997.201121988931
[generation of recombinant human antibodies for ev71 virus].to obtain recombinant human anti-ev71 antibodies from a ev71-associated hand-foot-and-mouth disease patient-derived antibody phage library.201121977579
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
A fatal case of enterovirus 71 infection with a single nucleotide variation in domain V of the 5' untranslated region. 201121997665
[the early diagnosis value of ev 71 igm class antibodies in the hand, foot and mouth disease].assessment of detection of igm antibodies for human enterovirus 71 (ev 71) in early diagnosis for the hand, foot and mouth disease (hfmd).201121863642
?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
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