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mcp-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells.vascular leakage, one hallmark of dengue haemorrhagic fever (dhf) and dengue shock syndrome, has been linked to the mediators secreted from cells in the circulatory system. in this study, extremely high expression levels of monocyte chemoattractant protein-1 (mcp-1) were found in the plasma of dhf patients compared with low mcp-1 expression levels in the plasma of enterovirus 71-infected patients. it was also found that mcp-1 expression was induced in dengue virus 2 (dv2)-infected monocytes and ...200617098977
long-term cognitive and motor deficits after enterovirus 71 brainstem encephalitis in children.several large outbreaks of enterovirus 71 infections have occurred in taiwan during the past decade. brainstem encephalitis was the most common neurologic complication. this study was designed to determine the long-term cognitive and motor outcomes of children with enterovirus 71 brainstem encephalitis.200617116698
echovirus 4 associated to hand, foot and mouth disease.hand, foot and mouth disease (hfmd) is a contagious enteroviral infection occurring primarily in children and characterized by vesicular palmoplantar eruptions and erosive stomatitis. echovirus 4 (ev-4) has been commonly associated with aseptic meningitis. the association of hfmd with ev-4 has not been reported previously. two samples of a 14-month child who presented mild fever, sores in the mouth, rash with blisters on the palm of hands and soles of feet were sent to enteric viruses laboratory ...200617119674
enterovirus surveillance--united states, 1970-2005.enteroviruses are common human viruses associated with various clinical syndromes, from minor febrile illness to severe, potentially fatal conditions (e.g., aseptic meningitis, paralysis, myocarditis, and neonatal enteroviral sepsis). multiple enterovirus serotypes exist. individual serotypes have different temporal patterns of circulation and often are associated with different clinical manifestations. changes in circulating serotypes might be accompanied by large-scale outbreaks.200616971890
integrated reverse transcription polymerase chain reaction systems for virus detection.the current study reports on an integrated microreverse transcription polymerase chain reaction (rt-pcr) system for molecular diagnosis of microorganisms automatically. by using antibodies-conjugated superparamagnetic beads, the developed system can detect viruses with higher sensitivity and specificity when compared with traditional biological diagnosis methods using a ribonucleic acid (rna) extraction kit. the target viruses were first captured by the conjugated antibodies on the magnetic bead ...200716978853
genetic diversity of enterovirus 71 isolated from cases of hand, foot and mouth disease in the 1997, 2000 and 2005 outbreaks, peninsular malaysia.all known field isolates of enterovirus 71 (ev71) can be divided into three distinct genogroups (a, b, c) and 10 subgenogroups (a, b1-5, c1-4) based on vp1 gene sequences. we examined vp1 gene sequences of 10, 12 and 11 ev71 strains isolated in peninsular malaysia during the outbreaks of hand, foot and mouth disease in 1997, 2000 and 2005 respectively. four ev71 strains isolated in the hand, foot and mouth disease outbreak of 2006 in sarawak (malaysian borneo) were included to describe their gen ...200719108398
epidemiologic and virologic investigation of hand, foot, and mouth disease, southern vietnam, 2005.during 2005, 764 children were brought to a large children's hospital in ho chi minh city, vietnam, with a diagnosis of hand, foot, and mouth disease. all enrolled children had specimens (vesicle fluid, stool, throat swab) collected for enterovirus isolation by cell culture. an enterovirus was isolated from 411 (53.8%) of the specimens: 173 (42.1%) isolates were identified as human enterovirus 71 (hev71) and 214 (52.1%) as coxsackievirus a16. of the identified hev71 infections, 51 (29.5%) were c ...200718217559
[study on the association of hand, foot and mouth disease and enterovirus 71/ca16 among children in beijing, 2007].to reveal the etiological agent of hand, foot and mouth disease in children in beijing.200718399150
differences in replication capacity between enterovirus 71 isolates obtained from patients with encephalitis and those obtained from patients with herpangina in taiwan.the cellular-tropism and biological characteristics of enterovirus 71 (ev71) isolates in taiwan (tw) were studied. growth curve experiments were conducted using cell lines that were possibly exhibited pathogenesis, and rt-pcr and sequencing tests were undertaken to amplify the 5' non-coding region (5'-ncr). the encephalitis isolate ev71 tw98ntu2078 was pbmc-tropic, temperature-resistant (tr) at 40 degrees c, and easier to replicate in htb-14 (astrocytoma) than the herpangina isolate ev71 tw98ntu ...200717133556
reticulon 3 binds the 2c protein of enterovirus 71 and is required for viral replication.enterovirus 71 is an enterovirus of the family picornaviridae. the 2c protein of poliovirus, a relative of enterovirus 71, is essential for viral replication. the poliovirus 2c protein is associated with host membrane vesicles, which form viral replication complexes where viral rna synthesis takes place. we have now identified a host-encoded 2c binding protein called reticulon 3, which we found to be associated with the replication complex through direct interaction with the enterovirus 71-encod ...200717182608
identification of neutralizing linear epitopes from the vp1 capsid protein of enterovirus 71 using synthetic peptides.enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease (hfmd) and has been associated with severe neurological diseases resulting in high mortalities. currently, there is no vaccine available and treatment is limited to palliative care. in this study, antisera were raised in mice against 95 overlapping synthetic peptides spanning the vp1 capsid protein of ev71. two peptides, sp55 and sp70, containing amino acid 163-177 and 208-222 of vp1, respectively, are capable of e ...200717222936
the correlation between neurological evaluations and neurological outcome in acute encephalitis: a hospital-based study.acute encephalitis is a common cns infectious disease in children. however, there are limited studies concerning about the correlation between the clinical evaluations and neurological outcome. to investigate the value of neurological evaluations, and the correlation between these evaluations and neurological outcomes of acute encephalitis, in the present study we retrospectively evaluated the neurological outcome of 0- to 16-year-old children with encephalitis or meningoencephalitis between 199 ...200717240177
antiviral effects of salvia miltiorrhiza (danshen) against enterovirus 71.in this study, the antiviral activities of seven different extracts of salvia miltiorrhiza (danshen) were determined. the first two extracts, sa1 and sa2, isolated at room temperature by ethyl acetate and water extraction, respectively, neutralized the enterovirus 71-induced cytopathic effect in vero, rhabdomyosarcoma and mrc-5 cells. the other five crude extracts, extracted with warm water (60-70 degrees c) or organic solvents, did not have any protective activity. the 50% inhibitory concentrat ...200717265559
the vp1 structural protein of enterovirus 71 interacts with human ornithine decarboxylase and gene trap ankyrin repeat.enterovirus 71 (ev71) is a major etiological agent of hand, foot and mouth disease (hfmd). several outbreaks in east asia were associated with neurological complications and numerous deaths. ev71 possesses four structural proteins vp1-vp4 that are necessary in the formation of the pentameric icosahedral capsid. the viral capsid contributes to virulence, and vp1 is a prime target for ev71 vaccine development. using yeast two-hybrid analysis, we demonstrated binding affinity between vp1 and three ...200717276651
human enterovirus 71 disease in sarawak, malaysia: a prospective clinical, virological, and molecular epidemiological study.human enterovirus (hev)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (cns) complications, but the role of hev-71 genogroups or dual infection with other viruses in causing severe disease is unclear.200717278054
enhanced potency and efficacy of 29-mer shrnas in inhibition of enterovirus 71.enterovirus 71 (ev71) is the main causative agent of hand, foot, and mouth disease (hfmd) in young children. it has been associated with severe neurological complications and has caused significant mortalities in large-scale outbreaks in asia. in this study, we demonstrated an enhanced silencing of ev71 through the use of chemically synthesized 29-mer shrnas. the 29-mer shrnas were designed to target three highly conserved regions of ev71 genome. transfection of rhabdomyosarcoma (rd) cells with ...200717316836
high-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the n-terminal portion of the capsid protein vp1.human enterovirus 71 has emerged as an important pathogen of children in the asia pacific region, and it may be important to consider the development of a vaccine against this virus. human cord serum was used as a source of neutralizing antibodies to determine whether the n- or c-terminal half of the vp1 capsid protein was more likely to harbour neutralizing determinants. cord sera from 205 individuals were tested for neutralizing antibodies against human enterovirus 71 in an indirect elisa agai ...200717318736
restoration of shoulder function and elbow flexion by nerve transfer for poliomyelitis-like paralysis caused by enterovirus 71 infection.we report the case of an eight-month-old girl who presented with a poliomyelitis-like paralysis in her left upper limb caused by enterovirus 71 infection. she recovered useful function after nerve transfers performed six months after the onset of paralysis. early neurotisation can be used successfully in the treatment of poliomyelitis-like paralysis in children.200717322446
genetic diversity of epidemic enterovirus 71 strains recovered from clinical and environmental samples in taiwan.most enteroviruses excreted in human feces and urine are present in environmental water. in order to clarify the infection route of enterovirus, the detection of viruses in both clinical and environmental samples may contribute to understanding the mode of transmission of strains responsible for human infection. thus, 21 epidemic enterovirus 71 strains from environmental water or stool samples were collected from hfmd children during 2005. enterovirus genomic rna was first amplified directly fro ...200717363101
neurodevelopment and cognition in children after enterovirus 71 infection.enterovirus 71 is a common cause of hand, foot, and mouth disease and encephalitis in asia and elsewhere. the long-term neurologic and psychiatric effects of this viral infection on the central nervous system (cns) are not well understood.200717377160
cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalitis and echovirus meningitis infections of varying severity.taiwan has experienced several outbreaks of enterovirus 71 (ev71) infections since 1998. this study examined the quantitative relationship between specific cytokines in the cerebrospinal fluid (csf) and the severity of ev71 brain stem encephalitis (be), and investigated whether the csf cytokine response differed from that to uncomplicated echovirus meningitis (em). the study included 57 children with ev71 be, of whom 24 had isolated be, 24 had autonomic nervous system (ans) dysregulation, and ni ...200717441979
dna vaccine constructs against enterovirus 71 elicit immune response in mice.enterovirus 71 (ev71) is a major causative viral agent responsible for large outbreaks of hand, foot and mouth disease (hfmd), a common rash illness in children and infants. there is no effective antiviral treatment for severe ev71 infections and no vaccine is available. the objectives of this study were to design and construct a dna vaccine against enterovirus 71 using the viral capsid protein (vp1) gene of ev71 and to verify the functionality of the dna vaccine in vitro and in vivo.200717445254
evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease.human enterovirus 71 and coxsackievirus a16 are important causes of hand-foot-and-mouth disease (hfmd). like other enteroviruses, they can be isolated from a range of sterile and nonsterile sites, but which clinical sample, or combination of samples, is the most useful for laboratory diagnosis of hfmd is not clear. we attempted virus culture for 2,916 samples from 628 of 725 children with hfmd studied over a 3 1/2-year period, which included two large outbreaks. overall, throat swabs were the si ...200717446325
rapid identification of emerging infectious agents using pcr and electrospray ionization mass spectrometry.newly emergent infectious diseases are a global public health problem. the population dense regions of southeast asia are the epicenter of many emerging diseases, as evidenced by the outbreak of nipah, sars, avian influenza (h5n1), dengue, and enterovirus 71 in this region in the past decade. rapid identification, epidemiologic surveillance, and mitigation of transmission are major challenges in ensuring public health safety. here we describe a powerful new approach for infectious disease survei ...200717470915
application of fluorescence resonance energy transfer resolved by fluorescence lifetime imaging microscopy for the detection of enterovirus 71 infection in cells.timely and effective virus infection detection is critical for the clinical management and prevention of the disease spread in communities during an outbreak. a range of methods have been developed for this purpose, of which classical serological and viral nucleic acids detection are the most popular. we describe an alternative, imaging-based approach that utilizes fluorescence resonance energy transfer (fret) resolved by fluorescence lifetime imaging microscopy (flim) and demonstrate it on the ...200717477731
genetic evolution of enterovirus 71: epidemiological and pathological implications.since its discovery in the 1970s, enterovirus 71 (ev71) has become one of the most pathogenic enterovirus serotypes causing recurrent outbreaks in different parts of the world. three waves of outbreaks globally have been recorded over the last three decades and more recently active circulation of ev71 is evident amongst countries in south east asia and beyond. there is evidence of a continuous evolution in its genetic make up which is likely to impact on its epidemiology and pathological potenti ...200717487831
genetic and antigenic analyses of enterovirus 71 isolates in taiwan during 1998-2005.enterovirus 71 (ev71) infections can lead to devastating clinical outcomes in children, with an increasing number of severe cases worldwide. the genetic and antigenic variability of ev71 strains isolated in taiwan in 1998-2005 was evaluated using partial nucleotide sequence analysis of the vp1 gene and the neutralisation assay. phylogenetic analyses revealed that most ev71 isolates from the 1998 epidemic belonged to sub-genogroup c2, with a minority belonging to sub-genogroup b4. between 1999 an ...200717488328
an attenuated strain of enterovirus 71 belonging to genotype a showed a broad spectrum of antigenicity with attenuated neurovirulence in cynomolgus monkeys.enterovirus 71 (ev71) is a causative agent of hand, foot, and mouth disease and is also sometimes associated with serious neurological disorders. in this study, we characterized the antigenicity and tissue specificity of an attenuated strain of ev71 [ev71(s1-3')], which belongs to genotype a, in a monkey infection model. three cynomolgus monkeys were inoculated with ev71(s1-3'), followed by lethal challenge with the parental virulent strain ev71(brcr-tr) via an intravenous route on day 45 postin ...200717567701
retrograde axonal transport: a major transmission route of enterovirus 71 in mice.inoculation of enterovirus 71 (ev71) by the oral (p.o.), intramuscular (i.m.), or intracranial route resulted in brain infection, flaccid paralysis, pulmonary dysfunction, and death of 7-day-old mice. the lag time of disease progression indicated that neuroinvasion from the inoculation sites was a prerequisite for the development of the clinical signs. although ev71 p.o. inoculation led to a persistent viremia and a transient increase in blood-brain barrier permeability at the early stage of the ...200717567704
enterovirus 71 triggering of neuronal apoptosis through activation of abl-cdk5 signalling.the molecular mechanism behind what causes an infection of enterovirus 71 (ev71) in young children to result in severe neurological diseases is unclear. herein, we show that cdk5, a critical signalling effector of various neurotoxic insults in the brain, is activated by ev71 infection of neuronal cells. ev71-induced neuronal apoptosis could be effectively repressed by blocking either cdk5 kinase activity or its protein expression. moreover, ev71-induced cdk5 activation was modulated by c-abl. th ...200717581253
[epidemiology of enterovirus associated with neurologic diseases].this report describes the results of human enterovirus (hev) detection and characterization using cell culture, polymerase chain reaction and molecular typing in 2167 samples obtained from acute flaccid paralysis, aseptic meningitis and acute encephalitis patients, from 1991 to 1998 in argentina. hev were isolated in 130 out of 666 cases (19.5%) and 36 out of 666 (5.4%). hev rna was detected in 28.8% (231/801) and 3.0% (21/700) of the patients with meningitis and encephalitis, respectively. chil ...200717593593
an eight-year study of epidemiologic features of enterovirus 71 infection in taiwan.in 1998, an epidemic of enterovirus 71 (ev 71) infection occurred in taiwan. the purpose of this study was to assess the epidemiology of ev 71 infection in taiwan. between march 1998 and december 2005, a total of 1,548 severe cases of hand-foot-mouth disease and herpangina (hfmd/ha) was reported to the center for disease control in taiwan. a seasonal variation in number of severe cases was observed, with the annual peak in second quarter. deaths from severe hfmd/ha varied from year to year (chi( ...200717620652
immunity to avirulent enterovirus 71 and coxsackie a16 virus protects against enterovirus 71 infection in mice.in this study, we sought to determine whether intratypic and intertypic cross-reactivity protected against enterovirus 71 (ev71) infection in a murine infection model. we demonstrate that active immunization of 1-day-old mice with avirulent ev71 strain or coxsackie a16 virus (ca16) by the oral route developed anti-ev71 antibodies with neutralizing activity (1:16 and 1:2, respectively). splenocytes from both ev71- and ca16-immunized mice proliferated upon ev71 or ca16, but not coxsackie b3 virus ...200717626076
ev71 induces vcam-1 expression via pdgf receptor, pi3-k/akt, p38 mapk, jnk and nf-kappab in vascular smooth muscle cells.enterovirus 71 (ev71) is a widespread virus that causes severe and fatal diseases in patients, including circulation failure. the mechanisms underlying ev71-initiated intracellular signaling pathways to influence host cell functions remain unknown. in this study, we identified a requirement for pdgfr, pi3-k/akt, p38 mapk, jnk, and nf-kappab in the regulation of vcam-1 expression by rat vascular smooth muscle cells (vsmcs) in response to viral infection. ev71 induced vcam-1 expression in a time- ...200717669626
epidemiologic features of hand-foot-mouth disease and herpangina caused by enterovirus 71 in taiwan, 1998-2005.in 1998, an epidemic of hand-foot-mouth disease/herpangina was caused by human enterovirus 71 infection in taiwan. the underlying factors of widespread emergence of viral infection are unclear. the purpose of this study was to assess the epidemiology of hand-foot-mouth disease/herpangina in taiwan between march 1998 and december 2005.200717671037
inhibition of enterovirus 71 in virus-infected mice by rna interference.enterovirus 71 (ev71) is the main causative agent of hand, foot, and mouth disease (hfmd) in young children. it is often associated with neurological complications and has caused high mortality levels in recent outbreaks in the asia pacific region. currently, there is no effective antiviral therapy against ev71 infections. in this study, we have evaluated and compared the efficacies of three different forms of small interfering rnas (sirnas) in inhibiting ev71 replication in a murine model. we h ...200717712333
enterovirus 71 meningoencephalitis during chemotherapy in a child with metastatic osteosarcoma.enterovirus meningoencephalitis is rare but can be severe. very few cases of these infections have been reported in pediatric oncology. we report the case of a 10-year-old boy with tibial osteosarcoma and lung metastases who developed enterovirus 71 meningoencephalitis during aplasia. clinical features comprised fever, hypotension, vesicular rash, generalized seizures, and altered consciousness. diagnosis was confirmed by polymerase chain reaction on samples of cerebrospinal fluid and skin vesic ...200717762499
ozone exposure in the culture medium inhibits enterovirus 71 virus replication and modulates cytokine production in rhabdomyosarcoma cells.in the present study, the effects of ozone exposure on enterovirus 71 (ev71) replication and related cytokine production were investigated. rhabdomyosarcoma cells (rd) were exposed to 0.5, 1, 1.5 and 2 ppm ozone or filtered air under different exposure regimens before or after infection for 1 or 2 h. the results revealed that at a proper concentration of ozone, e.g., 1.5 or 2 ppm, ozone exposure restricted virus production, prolonged survival time of cells and modulated cytokine production relat ...200717764758
outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge.similar to poliovirus, enterovirus type 71 (ev71) causes severe disease, including aseptic meningitis, encephalitis, acute flaccid paralysis, and acute cardiopulmonary dysfunction. large epidemics of ev71 infection have been reported worldwide.200717879907
passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing antibodies elicited by a synthetic peptide.enterovirus 71 (ev71) infections could lead to high mortalities and neither vaccine nor therapeutic treatment is available. we investigated vaccination with a synthetic peptide sp70 representing a neutralizing linear vp1 epitope of ev71 strain 41 (subgenogroup b4) and passive transfer of anti-sp70 antibodies to protect suckling balb/c mice against ev71 infectivity. when the mouse anti-sp70 antisera with a neutralizing antibody titer of 1:32 were passively administered to one-day-old suckling mic ...200717890123
asymptomatic circulation of hev71 in norway.widespread circulation of human enterovirus 71 was discovered in a prospective study of fecal samples obtained from healthy norwegian children. molecular characterization of the virus determined that it belonged to genotype c1. complete sequencing of this strain, hev71 804/no/03, revealed differences in the 5'utr and polymerase with respect to more pathogenic genotypes that may explain its reduced neurovirulence.200716965832
high immunogenic enterovirus 71 strain and its production using serum-free microcarrier vero cell culture.developing an effective vaccine against enterovirus 71 (ev71) infection provides the best means to control the disease. we have previously reported that large-scale preparation of a low immunogenic ev71 strain can be achieved using serum free microcarrier vero cell culture in a 2-l bioreactor [wu sc, liu cc, lian wc. optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development. vaccine 2004;22:3858-64]. this present work further investigated the v ...200716919374
inhibition of enterovirus 71 in virus-infected mice by rna interference.enterovirus 71 (ev71) is the main causative agent of hand, foot, and mouth disease (hfmd) in young children. it is often associated with neurological complications and has caused high mortality levels in recent outbreaks in the asia pacific region. currently, there is no effective antiviral therapy against ev71 infections. in this study, we have evaluated and compared the efficacies of three different forms of small interfering rnas (sirnas) in inhibiting ev71 replication in a murine model. we h ...200728182883
an integrated microfluidic system using magnetic beads for virus detection.an integrated system capable of sample pretreatment using antibody-conjugated magnetic beads and one-step reverse transcriptase-polymerase chain reaction (rt-pcr) on a microfluidic system was developed to accelerate the detection of rna viruses such as dengue virus or enterovirus 71. the targeted virus in the sample was first captured by the specific antibody-conjugated magnetic beads, which were manipulated by micro-electromagnets made of micro-electro-mechanical systems technology. the rna of ...200817911000
highly attenuated bordetella pertussis strain bpze1 as a potential live vehicle for delivery of heterologous vaccine candidates.bordetella pertussis, the causative agent of whooping cough, is a promising and attractive candidate for vaccine delivery via the nasal route, provided that suitable attenuation of this pathogen has been obtained. recently, the highly attenuated b. pertussis bpze1 strain has been described as a potential live pertussis vaccine for humans. we investigated here the use of bpze1 as a live vehicle for heterologous vaccine candidates. previous studies have reported the filamentous hemagglutinin (fha) ...200817954727
upper aerodigestive tract sequelae in severe enterovirus 71 infection: predictors and outcome.enterovirus 71 (ev71) infection sequelae can be severe and life-threatening, and long-term follow-up outcomes remain unknown. therefore, we conducted a retrospective follow-up study to review airway and neurological sequelae development in patients with severe ev71 infection. we also studied the incidence and risk factors for tracheotomy and gastrostomy requirement.200818029029
appearance of intratypic recombination of enterovirus 71 in taiwan from 2002 to 2005.genetic recombination is a well-known phenomenon for enteroviruses. in this study, we determined the phylogenetic relationships of five distinct regions of the ev71 genome for 73 ev71 isolates from 1986 and from 1998 to 2005 in taiwan. phylogenetic analyses showed that the 5'-utr, vp4-vp2, vp1, and 3d regions of ev71 isolated in 2004 and 2005 were grouped into genotype c. however, the 2b region of these isolates differed in that it grouped with genotype b, indicating recombination within ev71 ha ...200818036697
cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the nod/scid mouse infection model.enterovirus 71 (ev71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. an attenuated ev71 strain [ev71(s1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, sabin 1 [pv1(sabin)], in the 5' nontranslated region (ntr), 3d polymerase, and 3' ntr. in this study, we analyzed the effect of the attenuation determinants of ...200818057246
identification of immunodominant vp1 linear epitope of enterovirus 71 (ev71) using synthetic peptides for detecting human anti-ev71 igg antibodies in western blots.a major igg-specific immunodominant vp1 linear epitope of enterovirus 71 (ev71) strain 41 (5865/sin/00009), defined by the core sequence legttnpng, was identified by pepscan analysis. oligonucleotides corresponding to the amino-acid sequence of synthetic peptide sp32 were cloned and over-expressed in escherichia coli as a recombinant glutathione-s-transferase (gst)-sp32 fusion protein. in elisas, this protein did not react with human anti-ev71 igg antibodies, but there was significant immunoreac ...200818076666
a mammalian cell-based reverse two-hybrid system for functional analysis of 3c viral protease of human enterovirus 71.although several cell-based reporter assays have been developed for screening of viral protease inhibitors, most of these assays have a significant limitation in that numerous false positives can be generated for the compounds that are interfering with reporter gene detection due to the cellular viability. to improve, we developed a mammalian cell-based assay based on the reverse two-hybrid system to monitor the proteolytic activity of human enterovirus 71 (ev71) 3c protease and to validate the ...200818190777
antiviral activity of pyridyl imidazolidinones against enterovirus 71 variants.pyridyl imidazolidinone is a novel class of capsid binder which can inhibit enterovirus 71 (ev71). in this study, we tested the susceptibility of six recombinant viruses with different single-site mutations in vp1. eleven modified pyridyl imidazolidinones were synthesized and used to probe the interaction between these compounds and the ev71 vp1 protein. we found that the d31n or e98k mutant viruses were susceptible to bulkier compounds, which suggested that mutations at these two sites in vp1 m ...200818196474
molecular detection and prevalence of enterovirus within environmental water in taiwan.to investigate the presence of enterovirus rna in various samples of environmental water collected in taiwan during 2004-2005, and to characterize the genotypes and distribution of the viruses identified in taiwan.200818201176
recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71.the human enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in taiwan. enterovirus type 71 (ev71) plays a key role in patients with hand-foot-and-mouth disease (hfmd) combined with severe paralysis or encephalitis. it is important to find a method for preventing infection with ev71 since there is no antiviral agent or vaccine for humans. in this study, we developed a transgenic mouse model for demonstrating the protecti ...200818207613
first detection of enterovirus 71 from an acute flaccid paralysis case with residual paralysis in iran.in an attempt to determine the types of non-polio enteroviruses (npevs) in acute flaccid paralysis (afp) cases in iran, we detected enterovirus 71 (ev71) in an afp case with residual paralysis for the first time. cell culture detected no enteroviruses, while rt-pcr and subsequent sequencing revealed that the specimen was positive for ev71. ev71 is the causative agent of a variety of diseases from hand, foot and mouth disease to severe neurological complications and is now considered as an import ...200818403258
identification of human cd4 t-cell epitopes on the vp1 capsid protein of enterovirus 71.the identification of human cd4 t-cell epitopes within a protein vaccine candidate is of great interest,as it provides a better understanding of the mechanisms involved in protective immunity and may therefore help in the design of effective vaccines and diagnostic tools. the entire amino acid sequence of the vp1 capsid protein from enterovirus 71 (ev 71) strain 41 was submitted to analysis by the propred algorithm for the identification of potential promiscuous human cd4 t-cellepitopes. three r ...200818419256
acute encephalitis caused by intrafamilial transmission of enterovirus 71 in adult.enterovirus 71 (ev71) is a common cause of hand, foot, and mouth disease and sometimes causes severe neurologic complications, mainly in children. we report a case of adult-onset encephalitis caused by intrafamilial transmission of a subgenogroup c4 strain of ev71. this case elucidates the risk for ev71 encephalitis even in adults.200818439374
expression of vp1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection.enterovirus 71 (ev71) is the most common etiological agent detected in cases of hand-foot-and-mouth disease (hfmd) resulting in incidences of neurological complications and fatality in recent years. the clinical data have already shown the significant increase in recent ev71 epidemic activity throughout the asia-pacific region. due to the lack of an effective antiviral agent, primary prevention of the disease, including the development of an effective vaccine, has been the top priority in terms ...200818450335
[2008 guidelines for diagnosis and treatment of patients infected by enteric virus ev71]. 200818471350
pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis.we describe a model of enterovirus 71 encephalomyelitis in 2-week-old mice that shares many features with the human central nervous system (cns) disease. mice were infected via oral and parenteral routes with a murine-adapted virus strain originally from a fatal human case. the mice succumbed to infection after 2 to 5 days. vacuolated and normal-appearing cns neurons showed viral rna and antigens and virions by in situ hybridization, immunohistochemistry, and electron microscopy; inflammation wa ...200818520772
[the enter of viruses family picornaviridae in residents macrophages].viruses enter in cells through clathrin- and dinamin-mediated uptake route-endocytosis, caveolae-mediated local destruction of cell plasma membranes, and macropinocytosis. the non-enveloped viruses to which picornaviridae famiy is attributed are important human and animal pathogens. the aim of this study was to examine the mechanisms of penetration of viruses of this family (polio-, echo 11-, entero 71- and coxsackie b1-viruses) into resident macrophages. after attachment to the plasma membrane ...200818540199
the molecular basis of mouse adaptation by human enterovirus 71.a mouse-adapted strain of human enterovirus 71 (hev71) was selected by serial passage of a hev71 clinical isolate (hev71-26m) in chinese hamster ovary (cho) cells (cho-26m) and in newborn balb/c mice (mp-26m). despite improved growth in cho cells, cho-26m did not show increased virulence in newborn balb/c mice compared with hev71-26m. by contrast, infection of newborn mice with mp-26m resulted in severe disease of high mortality. skeletal muscle was the primary site of replication in mice for bo ...200818559932
design, synthesis, and evaluation of 3c protease inhibitors as anti-enterovirus 71 agents.human enterovirus (ev) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. a peptidomimetic inhibitor ag7088 was developed to inhibit the 3c protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond with the active site cys residue. in this study, we have prepared the recombinant 3c protease from ev71 (tw/2231/98), a particular strain which causes severe outbreaks in asia, and de ...200818583140
enterovirus 71 in taiwan, 2004-2006: epidemiological and virological features.we report unusual cases of myocarditis caused by enterovirus 71 (ev71) and a declining trend in the incidence of ev71 in taiwan since 2005. furthermore, phylogenetic analysis of the 5' untranslated region, vp4, and vp1 genes of ev71 isolates in 2004-2005 revealed a divergent phylogeny from the previous taiwanese isolates. no obvious phylogenetically distinct clones or clusters were found related to varying degrees of disease severity or clinical manifestations.200818584550
sheng-ma-ge-gen-tang inhibited enterovirus 71 infection in human foreskin fibroblast cell line.sheng-ma-ge-gen-tang (smggt), a popular prescription of chinese traditional medicine, has been used to manage measles infection of children for thousands of years. there are evidences to presume a wider spectrum of antiviral activity of smggt. however, smggt has not been proven to have activity against ev71 infection.200818601992
attention-deficit/hyperactivity-related symptoms among children with enterovirus 71 infection of the central nervous system.no study has investigated the association between enterovirus 71 central nervous system infection and symptoms related to attention-deficit/hyperactivity disorder. in this study we evaluated attention-deficit/hyperactivity disorder-related symptoms and internalizing problems as long-term sequelae resulting from enterovirus 71 central nervous system infection in children.200818606624
molecular epidemiology of human enterovirus 71 in the united kingdom from 1998 to 2006.the last decade witnessed a significant increase in epidemic activity of human enterovirus 71 (ev71) in the western pacific region (wpr). in most european countries, this risk is unrecognized despite occasional cases of severe disease and two severe outbreaks in eastern europe 30 years ago. in this study we report the first examination of the molecular epidemiology of ev71 in the united kingdom from 1998 to 2006. genomic regions encoding the 1d coat protein (vp1) and 3d polymerase (pol) from 32 ...200818650362
aloe-emodin is an interferon-inducing agent with antiviral activity against japanese encephalitis virus and enterovirus 71.in this study, aloe-emodin was identified as a potential interferon (ifn)-inducer by screening compounds from chinese herbal medicine. aloe-emodin showed low cytotoxicity to human hl-cz promonocyte cells and te-671 medulloblastoma cells and significantly activated interferon-stimulated response element (isre) and gamma-activated sequence (gas)-driven cis-reporting systems. moreover, aloe-emodin upregulated expression of ifn-stimulated genes such as dsrna-activated protein kinase and 2',5'-oligoi ...200818701259
the circulation of subgenogroups b5 and c5 of enterovirus 71 in taiwan from 2006 to 2007.enteroviruses (evs) are among the most common pathogens in humans. ev71 infections have caused devastating enterovirus-associated outcomes in children globally. in this study, eleven ev71 isolates in taiwan during 2006-2007 were selected for n-terminal vp1 gene analysis. a fragment of 403 bp on vp1 gene was sequenced and a phylogenetic analysis was performed. in addition, the full-length genome sequencing was carried out on two selected isolates. the results showed that subgenogroups of b5 and c ...200818706461
acute chemokine response in the blood and cerebrospinal fluid of children with enterovirus 71-associated brainstem encephalitis.brainstem encephalitis (be) is a serious neurological complication of enterovirus 71 (ev71) infection. the present study was designed to determine the characteristics of the chemokine response in the blood and cerebrospinal fluid (csf) of patients with ev71-associated be.200818710325
characteristics of bacterial and viral contamination of urban waters: a case study in xi'an, china.in order to gain knowledge on the presence of bacteria and viruses in urban waters, the authors started a long-term study on the microbiological quality of urban lakes and rivers in xi'an, china. in the current study, enteroviruses were chosen as typical viruses and rt-nested pcr was conducted for their detection. universal primers were designed for simultaneous detection of poliovirus, coxsackievirus, and enterovirus 71 which are the most frequently encountered enteroviruses in china. the rt-ne ...200818725735
prevalence of enteroviruses in hot spring recreation areas of taiwan.enteroviruses can be introduced into the water environment as a result of human activity. contaminations within hot tubs, spas and public baths are also possible. we investigated the distribution of enteroviruses at six hot spring recreation areas throughout taiwan. spring water was collected from 34 sites and enteroviruses were detected in 13 (38.2%). the most frequently detected was coxsackievirus a2, followed by echovirus 11. enterovirus 71 (ev 71) and porcine enterovirus 9 were detected once ...200818218023
the distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways.previous neuropathologic studies of enterovirus 71 encephalomyelitis have not investigated the anatomic distribution of inflammation and viral localization in the central nervous system (cns) in detail. we analyzed cns and non-cns tissues from 7 autopsy cases from malaysia and found cns inflammation patterns to be distinct and stereotyped. inflammation was most marked in spinal cord gray matter, brainstem, hypothalamus, and subthalamic and dentate nuclei; it was focal in the cerebrum, mainly in ...200818219253
ribavirin reduces mortality in enterovirus 71-infected mice by decreasing viral replication.enterovirus 71 (ev71) causes fatal encephalitis in young children. however, there is no effective antiviral drug available for infected patients. ribavirin is currently used for the treatment of several rna virus infections clinically, so its anti-ev71 efficacy was evaluated. in vitro results showed that ribavirin effectively reduced the viral yields (with an ic50 of 65 microg/ml) and virus-induced cytopathic effect in human and mouse cell lines. in vivo results showed that ribavirin reduced the ...200818279075
[serum types of enterovirus and clinical characteristics of 237 children with hand, foot and mouth disease in shenzhen].to study the clinical and epidemiologic characteristics and the serum types of enterovirus of hand, foot and mouth disease (hfmd) in children.200818289469
viral protein synthesis is required for enterovirus 71 to induce apoptosis in human glioblastoma cells.human glioblastoma cells (sf268) develop apoptosis, as characterized by dna fragmentation and caspase activation, upon infection with enterovirus 71 (ev71). to determine the step in virus replication that triggers apoptosis, the authors used ultraviolet (uv)-inactivated virus, inhibitors of protein and viral rna synthesis, and chloroquine to block virus uncoating. activation of caspase-3 was detected 24 h after infection with ev71 but not with uv-inactivated ev71. apoptosis was inhibited when ev ...200818300075
rapid detection of enterovirus 71 by real-time taqman rt-pcr.enterovirus 71 (ev71) is the main etiological agent of hand, foot and mouth disease (hfmd) and has been associated with neurological complications which resulted in fatalities during recent outbreaks in asia pacific region.200818304867
immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal challenge.enterovirus 71 (ev71) is an etiologic agent responsible for seasonal epidemics of hand-foot-and-mouth disease and causes outbreaks with significant mortality among young children. to develop the vaccine, we have produced and purified the ev71 virus-like particle (vlp) that resembles the authentic virus in appearance, capsid structure and protein composition. in this study, we further evaluated the potential of vlp as a vaccine by comparing the humoral and cellular immune responses elicited by th ...200818329759
development of multiplex real-time hybridization probe reverse transcriptase polymerase chain reaction for specific detection and differentiation of enterovirus 71 and coxsackievirus a16.large outbreaks of hand, foot, and mouth disease have been reported in the asia pacific region over the last few years and resulted in significant fatalities. the 2 main etiologic agents are enterovirus 71 (ev71) and coxsackievirus a16 (ca16). both viruses are closely related genetically and show similar clinical symptoms. however, ev71 are associated with neurologic complications and can lead to fatalities. in this study, we developed a multiplex real-time hybridization probe reverse transcript ...200818394844
glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection.variations in the cellular microenvironment affect the host's susceptibility to pathogens. using glucose-6-phosphate dehydrogenase (g6pd)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (ev71) infection. compared with their normal counterparts, g6pd-deficient cells supported ev71 replication more efficiently and showed greater cytopathic effect and loss of viability. mechanistically, viral infec ...200818753216
isolating asian enterovirus 71 subgenogroup c4 in two austrian clinical samples from 2004. 200818761929
a study of acute febrile encephalopathy with special reference to viral etiology.to study the etiological profile of patients with acute febrile encephalopathy syndrome focusing chiefly on the viral etiology, and to correlate clinical and radiological features of patients with viral encephalitis.200818769890
characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity.poliovirus (pv) and enterovirus 71 (ev71) cause severe neurological symptoms in their infections of the central nervous system. to identify compounds with anti-pv and anti-ev71 activities that would not allow the emergence of resistant mutants, we performed drug screening by utilizing a pharmacologically active compound library targeting cellular factors with pv and ev71 pseudoviruses that encapsidated luciferase-encoding replicons. we have found that metrifudil (n-[2-methylphenyl]methyl)-adenos ...200818796721
heterogeneous nuclear ribonuclear protein k interacts with the enterovirus 71 5' untranslated region and participates in virus replication.enterovirus 71 (ev71) is a picornavirus that can cause severe neurological complications in children. like other picornaviruses, the genomic rna of ev71 contains a long 5' untranslated region (utr). cellular proteins interact with the ev71 5' utr, and these interactions are important for virus replication. using an rna pull-down assay and proteomics approaches, this study identified the heterogeneous nuclear ribonucleoprotein k (hnrnp k) as one of the ev71 5' utr-associated proteins. the interac ...200818796723
enterovirus 71 infection: a new threat to global public health? 200818848307
hemorrhagic stroke associated with pulmonary edema and catastrophic cardiac failure.cerebral arteriovenous fistula (avf) is a vascular malformation that is rare in the pediatric population. older children with cerebral avf tend to present with neurologic problems related to intracranial venous hypertension or intracranial hemorrhage. cardiac and pulmonary complications following acute neurologic injury such as subarachnoid hemorrhage are common in adults, but are rarely reported in children. however, complications have been reported in cases of enterovirus 71 rhombencephalitis ...200818947007
amantadine as a regulator of internal ribosome entry site.studies of eukaryotes have yielded 2 translation initiation mechanisms: a classical cap-dependent mechanism and a cap-independent mechanism proceeding through the internal ribosomal entry site (ires). we hypothesized that it might be possible to identify compounds that may distinguish between cap-dependent translation and cap-independent ires-mediated translation.200818954527
[a case with hand, foot and mouth disease associated with central nervous symptoms related to enterovirus 71 in beijing]. 200819099718
[pay much attention to severe enterovirus 71 infection in children]. 200819099772
[three cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation].to recognize the clinical features of the enterovirus 71 (ev71) infection with pulmonary edema or pulmonary hemorrhage as a fulminant and often fatal illness.200819099810
[genotype analysis of enterovirus type 71 detected from patients with hand-foot-mouth disease in shenzhen].to carry out genotype analysis of enterovirus type 71, detected from hand-foot-mouth disease patients in shenzhen in 2004.200819103116
hla-a33 is associated with susceptibility to enterovirus 71 infection.enterovirus 71 has caused large epidemics of disease, resulting in many fatalities and severe sequelae, in taiwan and some other countries. in this study, host genetic factors were investigated to link susceptibility to and clinical severity of enterovirus 71 infections.200819047245
detection and quantification of enterovirus 71 genome from cerebrospinal fluid of an encephalitis patient by pcr applications.enterovirus 71 (ev71) is one of the causative agents of hand, foot, and mouth disease (hfmd) and is known to cause encephalitis, but several reports have identified ev71 in cerebrospinal fluid (csf). we detected ev71 in csf from a 20-month-old infant. the patient was diagnosed with brainstem encephalitis associated with hfmd. the clinical features of the patient were high fever (39.1c) and myoclonic jerks, and magnetic resonance imaging of the brain showed a bright signal area around the 4th ven ...200819050366
enterovirus 71 in taiwan.the enterovirus 71 (ev71) outbreak in taiwan in 1998 proved fatal in many children. a seroepidemiological study performed prior to the 1998 outbreak showed pre-epidemic (1997) ev71 seroprevalence rates to be about 60-70% in adults and children older than 6 years of age. a retrospective case review carried out from 1980-81 identified 16 cases of hand, foot and mouth disease associated with central nervous system involvement, two of whom died soon after hospitalization. there were 405 severe cases ...200819054914
enterovirus 71, one virus and many stories.enterovirus 71 (ev71) has emerged as a significant cause of brainstem encephalitis and acute flaccid paralysis in taiwan. it may be complicated by autonomic nervous system dysregulation and pulmonary edema (pe). cytokines in the central nervous system and systemic inflammatory responses play important roles in the pathogenesis of ev71-associated pe. pathogenesis-based management with intravenous immunoglobulin and milrinone has been associated with reduced mortality in children with severe ev71 ...200819054915
a water extract of pueraria lobata inhibited cytotoxicity of enterovirus 71 in a human foreskin fibroblast cell line.enterovirus 71 (ev71) can cause brain encephalitis and mortality. however, effective vaccines or chemotherapeutic agents are not yet available. we tested the hypothesis that pueraria lobata could inhibit the cytotoxic effect of ev71 in a human foreskin fibroblast cell line by the xtt method. our results showed that the water extract of p. lobata could inhibit cytopathy induced by ev71 when given before (p < 0.0001), simultaneously with (p < 0.0001), or after viral infection (p < 0.0001). water e ...200819181583
[study of the clinical and laboratory features of hand-foot-mouth disease].to study the clinical and laboratory features of the mild and severe hand-foot-mouth diseases (hfmd) in shenzhen in 2008.200819544650
[expression of recombinant vp1 protein of enterovirus 71 and development of serological assay for detection of ev71 infection].to obtain a recombinant purified enterovirus 71 vpi protein and establishment of an early, rapid and accurate serological elisa (enzyme-linked immunosorbent assay) for detection of ev71 infection.200819544656
an adult case of hand, foot, and mouth disease caused by enterovirus 71 accompanied by opsoclonus myoclonica.we reported a 23-year-old female who was treated for rash due to hand, foot, and mouth disease (hfmd). on day 4 of hospitalization, the patient showed opsoclonus (jerky eye movements in all directions), myoclonus of the neck, trunk, and extremities, and cerebellar ataxia. based on the changes in serum viral antibody titer, the patient was diagnosed as enterovirus 71 infection. no obvious abnormal findings were noted in head mri. immunoglobulin 5 g/day was administered for 3 days in the early sta ...200821318985
[clinical features and treatment of serious brainstem encephalitis caused by enterovirus 71 infection].to study the clinical features and treatment of serious brainstem encephalitis caused by enterovirus 71 (ev71) infection.200920113599
diseases caused by enterovirus 71 infection.the purpose of this review was to explore the epidemiology, pathogenesis, virology, and management of enterovirus 71 (ev71) infection. published literature was surveyed by medline using the keyword "ev71." the reported incidence of cases of hand-foot-mouth disease/herpangina varied from year to year; seasonal variations in incidence were observed, with a peak in incidence during the summer season. most cases of hand-foot-mouth disease/herpangina hospitalized for complications occurred in childre ...200920118685
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