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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
therapeutic efficacy of milrinone in the management of enterovirus 71-induced pulmonary edema.hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (ev71) infections. brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. this study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (pde) inhibitor, in the treatment of patients with ev71-induced pulmonary edema. we conducted a historically controlled trial of 24 children with severe ev71-induced pulmonary edema fr ...200515635619
specific detection of enterovirus 71 directly from clinical specimens using real-time rt-pcr hybridization probe assay.enterovirus 71 (ev71) is one of the main causative agents of hand, foot and mouth disease (hfmd) in young children. infections caused by ev71 could lead to many complications, ranging from brainstem encephalitis to pulmonary oedema, resulting in high mortality. thus, rapid detection of the virus is required to enable measures to be implemented in preventing widespread transmission. based on primers and probes targeting at the vp1 region, a real-time reverse-transcriptase polymerase chain reactio ...200616460910
microchip, reverse transcription-polymerase chain reaction and culture methods to detect enterovirus infection in pediatric patients.enterovirus infection usually presents with mild and self-limited illness in children. however, enterovirus type 71 can be characterized by neurotropism and may cause severe illness or even sudden death. early detection of the virus will allow a physician to provide intensive or aggressive intervention. the purpose of the present study was to compare sensitivity of two innovative laboratory methods, that is, the dr.ev microchip method (dr. chip biotechnology, shin-tsu, taiwan) and the reverse tr ...200616490062
expression, purification and characterization of enterovirus-71 virus-like particles.enterovirus 71 (ev71) has been implicated as the etiological agent responsible for the recent outbreaks of hand, foot and mouth disease associated with severe neurological diseases in the asia-pacific region.200616521221
the vp1 protein of human enterovirus 71 self-associates via an interaction domain spanning amino acids 66-297.enterovirus 71 (ev71) is a major etiological agent of hand, foot, and mouth disease (hfmd). several recent outbreaks of hfmd in east asia were associated with neurological complications and numerous deaths. in 2000, an outbreak in singapore afflicted thousands of children, resulting in four fatal cases from whom ev71 was isolated. the virus possesses four structural proteins vp1, vp2, vp3, and vp4, each of which is involved in forming the pentameric icosahedral structure of the virus. here we re ...200616555287
current status of anti-picornavirus therapies.picornaviruses are important human pathogens causing severe morbidity and some mortality with the potential to cause worldwide crippling disease. currently, there are few treatments for many of the viruses in the picornaviridae, for rhinoviruses, there are no approved treatments, although ruprintrivir looks promising in clinical trials and pyridazinyl oxime ethers may prove useful. poliovirus treatments are needed to supplement the world health organization's polio eradication plan in order to t ...200616611122
molecular typing of enteroviruses associated with viral meningitis in cyprus, 2000-2002.human enteroviruses are responsible for a wide spectrum of clinical diseases affecting many different organ systems. although infection is usually asymptomatic, infections of the central nervous system manifested as meningitis or encephalitis can pose a serious public health problem, especially during outbreaks. in this study, samples from 218 patients diagnosed with enteroviral meningitis between january 2000 and december 2002 were analysed in order to assess the epidemiology of human enterovir ...200616849723
enterovirus 71 infection induces fas ligand expression and apoptosis of jurkat cells.t-cell depletion is found in enterovirus 71 (ev71)-infected patients with pulmonary edema. however, the mechanism that causes t-cell depletion is unclear. to address this question, the effects of ev71 infection on the cell viability of human jurkat t cells were studied. viable viruses were recovered from both the culture supernatant and the cell lysate of jurkat cells after ev71 infection. results from reverse-transcription polymerase chain reaction (rt-pcr) and immunofluorescence assay confirme ...200616628611
[isolation and sequencing of vp1 region of enterovirus 71 strains in zhejiang, china].to study the gene characterization of enterovirus 71 (ev71) virus strains isolated from clinical specimens of children with hand-foot-and-mouth disease (hfmd) in zhejiang province.200516676593
modulation of cytokine production by intravenous immunoglobulin in patients with enterovirus 71-associated brainstem encephalitis.several epidemics of enterovirus 71 (ev71) infections occurred in taiwan since 1998.200616861032
molecular epidemiology of enterovirus 71 over two decades in an australian urban community.enterovirus 71 (ev71), first isolated in 1969, has been responsible for numerous outbreaks of hand, foot and mouth disease (hfmd) with a small proportion of cases associated with neurological disease. since 1997 there has been a significant increase in both the prevalence and virulence of ev71 in the asia-pacific region. we have examined the genetic diversity of ev71 in a large australian city (sydney n.s.w.) over a nineteen-year period. we determined the vp1 gene sequence of forty-eight ev71 st ...200616369861
percutaneous cardiopulmonary support in a child with enterovirus 71 encephalitis. 200616732804
structure of the virus capsid protein vp1 of enterovirus 71 predicted by some homology modeling and molecular docking studies.the homology modeling technique has been used to construct the structure of enterovirus 71 (ev 71) capsid protein vp1. the protein is consisted of 297 amino acid residues and treated as the target. the amino acid sequence identity between the target protein and sequences of template proteins 1eah, 1piv, and 1d4m searched from ncbi protein blast and workbench protein tools were 38, 37, and 36%, respectively. based on these template structures, the protein model was constructed by using the insigh ...200616868986
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
polioviruses and other enteroviruses isolated from faecal samples of patients with acute flaccid paralysis in australia, 1996-2004.acute flaccid paralysis (afp) is the most common clinical presentation of acute poliovirus infection, occurring in 0.1-1% of infected cases. afp surveillance has been used world-wide to monitor the control and eradication of circulating wild poliovirus. this study aims to review the significance of all enteroviruses, including polioviruses, isolated from patients with afp in australia between 1996 and 2004.200616737480
status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71.we valuated specific cellular and humoral immune response of cases of enterovirus 71 (ev71) infection and correlated immune response with clinical outcome. after obtaining informed consent, we enrolled 30 ev71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of cns (cns) involvement and 11 uncomplicated cases. we measured antibodies specific to ev71, lymphocyte proliferation response and ev71-stimulated cellular response of th1/th2 cytokines and chemokines. the ...200616940249
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
evolution of ev71 genogroup in taiwan from 1998 to 2005: an emerging of subgenogroup c4 of ev71.in taiwan, enterovirus 71 (ev71) has played an important role in severe enterovirus-related cases every year since the devastating outbreak in 1998. three genogroups a, b, c occur worldwide; with the b and c genogroups being subdivided into b1-b4 and c1-c4 subgenogroups respectively. to understand the mutation of the ev71 genogroup in taiwan before and after 1998, a total of 54 worldwide strains were studied including 41 taiwanese strains obtained in 1986 and 1998-2004. a fragment of 207 bp of t ...200616372302
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
combining multiplex reverse transcription-pcr and a diagnostic microarray to detect and differentiate enterovirus 71 and coxsackievirus a16.cluster a enteroviruses, including enterovirus 71 (ev71) and coxsackievirus a16 (ca16), are known to cause hand-foot-and-mouth disease (hfmd). despite the close genetic relationship between these two viruses, ev71 is generally known to be a more perpetuating pathogen involved in severe clinical manifestations and deaths. while the serotyping of enteroviruses is mostly done by conventional immunological methods, many clinical isolates remain unclassifiable due to the limited number of antibodies ...200616757623
recombinant newcastle disease virus capsids displaying enterovirus 71 vp1 fragment induce a strong immune response in rabbits.the complete vp1 protein of ev71 was truncated into six segments and fused to the c-terminal ends of full-length nucleocapsid protein (npfl) and truncated np (npt; lacks 20% amino acid residues from its c-terminal end) of newcastle disease virus (ndv). western blot analysis using anti-vp1 rabbit serum showed that the n-terminal region of the vp1 protein contains a major antigenic region. the recombinant proteins carrying the truncated vp1 protein, vp1(1-100), were expressed most efficiently in e ...200616789020
sentinel surveillance for human enterovirus 71 in sarawak, malaysia: lessons from the first 7 years.a major outbreak of human enterovirus 71-associated hand, foot and mouth disease in sarawak in 1997 marked the beginning of a series of outbreaks in the asia pacific region. some of these outbreaks had unusually high numbers of fatalities and this generated much fear and anxiety in the region.200616827926
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
effects of ozone exposure on inactivation of intra- and extracellular enterovirus 71.in this study, the potential of ozone in inactivating enterovirus 71 (ev71) free particles was investigated using either various ozone flow rates of 100, 80 or 60 mg/h or a constant flow rate of 80 mg/h, given to culture medium or various ph culture media containing ev71, respectively. results demonstrated that ev71 inactivation by ozone was related to the kinetics of ozone solubility, approximately 99% inactivation being obtained in the exponential phase of ozone solubility. however, the inacti ...200616838411
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
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
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
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
[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
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
the complete genome of enterovirus 71 china strain.five overlapping clones covering the full genome of enterovirus 71 china strain shzh98 were obtained and then the sequences were determined by the chain termination method. it showed that the full length of ev71 shzh98 genome (not including poly a tail) is 7408 bp. there are some diversities on the lengths and sequences of 5' utr and 3' utr between shzh98 and the other ev71 strains. in p1 capsid region, which is closely associated with viral immunogenicity, ev71 strain shzh98 shares the highest ...200118726435
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
emerging and re-emerging viruses in malaysia, 1997-2007.over the past decade, a number of unique zoonotic and non-zoonotic viruses have emerged in malaysia. several of these viruses have resulted in significant morbidity and mortality to those affected and they have imposed a tremendous public health and economic burden on the state. amongst the most devastating was the outbreak of nipah virus encephalitis in 1998, which resulted in 109 deaths. the culling of more than a million pigs, identified as the amplifying host, ultimately brought the outbreak ...200919010076
far upstream element binding protein 2 interacts with enterovirus 71 internal ribosomal entry site and negatively regulates viral translation.an internal ribosomal entry site (ires) that directs the initiation of viral protein translation is a potential drug target for enterovirus 71 (ev71). regulation of internal initiation requires the interaction of ires trans-acting factors (itafs) with the internal ribosomal entry site. biotinylated rna-affinity chromatography and proteomic approaches were employed to identify far upstream element (fuse) binding protein 2 (fbp2) as an itaf for ev71. the interactions of fbp2 with ev71 ires were co ...200919010963
real-time monitoring of human enterovirus (hev)-infected cells and anti-hev 3c protease potency by fluorescence resonance energy transfer.a real-time assay system that allows monitoring of intracellular human enterovirus (hev) protease activity was established using the principle of fluorescence resonance energy transfer (fret). it was accomplished by engineering cells to constitutively express a genetically encoded fret probe. the fret-based probe was designed to contain an enterovirus 71 3c protease (3c(pro)) cleavage motif flanked by the fret pair composed of green fluorescent protein 2 and red fluorescent protein 2 (dsred2). e ...200919015331
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
simultaneous detection of human enterovirus 71 and coxsackievirus a16 in clinical specimens by multiplex real-time pcr with an internal amplification control.the recent and continuing hfmd outbreak caused by ev71 in several provinces of china since march 2008 has affected thousands of children and resulted in nearly 50 deaths. in this study, a sensitive and specific multiplex real-time rt-pcr assay has been developed for the rapid detection of ev71 and cv-a16. by using an internal amplification control, the real-time assay achieves detection of samples containing inhibitors and avoids false negatives. it should prove useful for clinical diagnosis of ...200919057836
antiviral activity of raoulic acid from raoulia australis against picornaviruses.rna viruses are a major source of respiratory diseases worldwide. the lack of effective therapeutical treatment underlines the importance of research for new antiviral compounds. raoulic acid is a principal ingredient of the plant raoulia australis hook. f. antiviral assay using cytopathic effect (cpe) reduction method showed that raoulic acid possessed strong antiviral activity against human rhinovirus 2 (hrv2) with a 50% inhibition concentration (ic(50)) value of less than 0.1mug/ml, human rhi ...200919097770
[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
epidemiology of enterovirus types causing neurological disease in austria 1999-2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes.between 1999 and 2007 1,388 stool specimens from patients with acute flaccid paralysis or aseptic meningitis were submitted to the austrian reference laboratory for poliomyelitis. samples (201) yielded non-poliovirus enterovirus in culture. one hundred eighty-one viruses were available for typing and 78 isolates which remained serologically untyped were further analyzed by codehop-pcr and sequencing of the vp1 gene and the 5'-untranslated region (5'-utr). typing revealed an echovirus 30 outbreak ...200919107980
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
enterovirus 71 outbreak, brunei.enterovirus 71 (ev71) outbreaks occur periodically in the asia-pacific region. in 2006, brunei reported its first major outbreak of ev71 infections, associated with fatalities from neurologic complications. isolated ev71 strains formed a distinct lineage with low diversity within subgenogroup b5, suggesting recent introduction and rapid spread within brunei.200919116058
direct identification of human enterovirus serotypes in cerebrospinal fluid by amplification and sequencing of the vp1 region.human enteroviruses (hev) are a major cause of meningitis and other neurological disease. identification of hev serotypes in clinical cases is important for monitoring emergence of more pathogenic variants, epidemiological surveillance and investigating sources of infection. serotype identification is currently problematic following the widespread adoption of polymerase chain reaction (pcr)-based methods for hev detection in place of virus culture.200919135410
identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in sarawak.human enterovirus 71 (hev71) can cause hand, foot, and mouth disease (hfmd) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. early recognition of children at risk is the key to reduce acute mortality and morbidity.200919152683
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