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analysis of recombination and natural selection in human enterovirus 71.the development of effective vaccines and antiviral prophylaxis against human enterovirus 71 (ev71) has been hampered by the extensive antigenic diversity of the virus. to gain new insights into the evolutionary processes that create this genetic diversity, the treeorder scan method and rdp program were employed to detect recombination events in the genome, and then parsimony-based and maximum-likelihood-based methods were used to detect natural selection effects on viral proteins. recombination ...201020060995
rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection.to evaluate the suitability of rupintrivir against enterovirus 71 (ev71) induced severe clinical symptoms using computational methods.201020066739
endoplasmic reticulum stress is induced and modulated by enterovirus 71.picornavirus infection alters the endoplasmic reticulum (er) membrane but it is unclear whether this induces er stress. infection of rhabdomyosarcoma cells with enterovirus 71 (ev71), a picornavirus, caused overexpression of the er-resident chaperone proteins, bip and calreticulin, and phosphorylation of eif2alpha, but infection with uv-inactivated virus did not, indicating that er stress was induced by viral replication and not by viral attachment or entry. silencing (si)rna knockdown demonstra ...201020070307
[seroepidemiology investigation of hev71 in healthy children of 1-6 years old in three counties of china in 2005].to investigate human enterovirus 71(hev71) antibody levels among children in china in recent years, to find the epidemic status of hand, foot and mouth diseases (hfmd) in children, and to provide a scientific base for the hfmd prevention and control.200920077660
[multiple viral transmission chains of human enterovirus 71 co-circulated in gansu province in 2008].to study the molecular evolution of human enterovirus 71 (hev71) isolated from clinical specimens of hand, foot and mouth disease (hfmd)patients in gansu in 2008.200920077673
[human enterovirus 71 was isolated from specimens of hand foot mouth disease in beijing in 2007].analyzing and identifying the type of enterovirus of human hand foot mouth disease (hfmd) outbreak in daxing district in beijing at the end of may in 2007.200920077674
[coxsackievirus a group 16 strain].coxsackievirus a group 16 strain (cva16) is one of the predominate causative agent of the hand, foot and mouth disease (hfhd). it is very helpful to improve the hand, foot and mouth disease and other associated diseases control and prevention by understanding its biological characteristics, pathogenic mechanism and clinical manifestations, laboratory diagnoses, epidemiology and molecular epidemiology. in the future, we should continue to emphasize the study, improve the diagnostic method and dev ...200920077682
[genetic characterization of vp4-vp2 of two coxsackievirus a4 isolated from patients with hand, foot and mouth disease].to study the genetic characteristic of vp4-vp2 of coxsackievirus a4 (cva4) isolated from clinical specimens of patients with hand, foot and mouth disease (hfmd) in gansu in 2008.200920077736
[genotype distribution of enterovirus a species isolated in shandong province, china].in order to study the genotypes and molecular evolution of human enterovirus (hev) a species in shandong province, stool samples were collected from afp and hfmd patients in shandong province and virus isolation was performed. reverse transcription-polymerase chain reactions (rt-pcr) specific for ev71 and cva16 were performed with the virus isolates from hfmd patients. positive isolates were selected for entire vp1 coding gene amplification and sequencing. isolates with negative pcr results and ...200920077929
[genetype characteristics of enterovirus type 71 in shenzhen from 2005 to 2008].genetic characteristics of enterovirus type 71 in shenzhen from 2005 to 2008 were analyzed. all samples were detected by rt-pcr using ev71-specific primers. the vp1s of ev71 strains were amplified and sequenced. a phylogenetic tree was constructed by comparison of the sequences with those of subgenotype a, b and c using dnastar, bioedit and mega 3.1 softwares. the vp1 nucleotide sequences of 17 strains of shenzhen shared 95.3%-99.4% identities with cluster c4a, and one strain shared 93.0%-95.6% ...200920077930
[analysis on the preference of synonymous codon in vp1 nucleotide sequence of the ev71 based on rscu method].based on rscu method and by analyzing the preference of codon usage in vp1 nucleotide sequences of ev71 isolated in chinese mainland and taiwan region from 1998 to 2008, it is clear that there is an obvious time discrimination in rscu calculated from ev71 vp1 strain between two different regions of china and it is more obvious in taiwan region, therefore, according to the diversity of rscu, the years can be divided into 2 intervals in chinese mainland and 4 intervals in taiwan region, especially ...200920077938
[changes of immune function in patients with enterovirus 71 infection].to investigate the association of changes in immune function with enterovirus 71 (ev71) cases with different severity of the disease.200920078993
inhibition of enterovirus 71 replication and the viral 3d polymerase by aurintricarboxylic acid.enterovirus 71 (ev71) causes serious diseases in humans. the aim of this study was to examine the effects of aurintricarboxylic acid (ata) on ev71 replication and to explore the underlying mechanism.201020089540
evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the vp1 gene.human enterovirus 71 (ev-71) is one of the major etiologic causes of hand, foot, and mouth disease (hfmd) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. global vp1 capsid sequences (n = 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods. we estimated that the common ancestor of human ev-71 likely emerged around 1941 (95% confi ...201020089660
glucocorticoid and pyrazolone treatment of acute fever is a risk factor for critical and life-threatening human enterovirus 71 infection during an outbreak in china, 2008.human enterovirus 71 (hev71) causes outbreaks of life-threatening diseases throughout the world. the genesis of these severe diseases is unknown.201020104199
[seroepidemical study of coxsackievirus a 16, in four provinces, china, 2005].to study the situation of 1- 5-years-old children's antibody against coxsackievirus a group 16 strain (cva16) in guangdong, heilongjiang,yunnan province and xinjiang uygur autonomous regions, china, 2005, it can offer scientific evidences for preventing and controlling cva16 causative hand-food and mouth disease.200920104748
development of enterovirus 71 vaccines.enterovirus 71 (ev71) was first isolated in 1969 in california, usa. several epidemic outbreaks with high mortality rates have occurred in european and asian countries (bulgaria in 1975, hungary in 1978, malaysia in 1997, taiwan in 1998 and china in 2008). ev71 cns involvement may be associated with neurological sequelae, delayed neurodevelopment and reduced cognitive functioning. since poliovirus was nearly eradicated by vaccination, ev71 is now considered as one of the top candidates for new v ...201020109026
[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
effects of herbal medicinal formulas on suppressing viral replication and modulating immune responses.the chinese medicinal herbs radix isatidis and viola yedoensis makino have been suggested to possess antiviral activity. this study tests whether these and other chinese and western herbal medicinal formulas can modulate the immune functions involving virus-suppression in balb/c mouse. we first confirmed the extract from viola yedoensis makino, but not from radix isatidis, the traditional chinese medicine (tcm) formula chui-uren-chien (cuc), or a western homeopathic medicinal drink método canova ...201020128053
in vitro anti-enterovirus 71 activity of gallic acid from woodfordia fruticosa flowers.the anti-enterovirus 71 (ev71) activity of six nepalese plants' extracts and gallic acid (ga) isolated from woodfordia fruticosa kurz (family; lythaceae) flowers were evaluated in vero cells.201020149083
the cross-reactivity of the enterovirus 71 to human brain tissue and identification of the cross-reactivity related fragments.ev71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. however, the neurological destruction mechanism was remained to be clarified. this study described the cross reaction between ev71 induced igg and human brain tissue.201020170551
[study on the etiology of hand-foot-mouth disease outbreaks in beijing in 2007].to identify the etiology of 8 human hand-foot-mouth disease (hfmd) outbreaks in beijing, during may to july 2007.200920193198
[detection of enterovirus rna by fluorescent quantitative pcr in children with hand-foot-mouth disease]. 201020199735
epidemiologic features and virus isolation of enteroviruses in northern taiwan during 2000-2008.the susceptibility of five cell lines, rd, mrc-5, mk-2, hep-2 and a549, for various serotypes of human enteroviruses was evaluated. rd cells were susceptible to most serotypes of enteroviruses, especially for human enterovirus a. consequently, a high prevalence of human enterovirus a in taiwan may reflect the relative importance of rd cells in the clinical virology laboratory. however, susceptibilities of rd cells to coxsackievirus a9 and a24, and echovirus 9 and 11 were exceptionally low. alter ...201020214926
[identification of an enterovirus 71 receptor; scarb2].enterovirus 71 (ev71) and coxsackievirus a16 (cva16), belonging to family picornaviridae, genus enterovirus, species a, are causative agents of hand-foot-mouth disease (hfmd). infections involving ev71, but not cva16, can progress to severe neurological disease, including aseptic meningitis, encephalitis, acute flaccid paralysis and neurogenic pulmonary edema. ev71 is thus considered to be a neuropathogenic virus and ev71 outbreak has become a major public health concern. human rd cells are high ...200920218327
[identification of p-selectin glycoprotein ligand-1 as one of the cellular receptors for enterovirus 71].enterovirus 71 (ev71) is a major causative agent of hand, foot and mouth disease (hfmd), a common febrile disease in young children. although clinical manifestations of hfmd are usually mild and self-limiting, ev71 can cause large outbreaks of hfmd including severe neurological complications. we identified human p-selectin glycoprotein ligand-1 (psgl-1; cd162) as a functional receptor for ev71 using an expression cloning method with a human t cell cdna library by panning. psgl-1 is a sialomucin ...200920218328
knowledge about and attitude toward enterovirus 71 infections: a survey of parents and teachers at kindergartens in taiwan.in 2008, we surveyed 690 parents and 104 teachers at kindergartens in taiwan about their knowledge of and attitude towards enterovirus 71 infections. the accurate response rate for enterovirus infection characteristics was greater than 80% for specific symptoms, prevalent age group, and predominant infection season. parents and teachers felt great anxiety and even panic about infection. both groups perceived the impact of enterovirus infection to be worse than that of influenza.201020227791
transcriptome profiling of host-microbe interactions by differential display rt-pcr.in recent years, dna microarray has become increasingly popular as a tool to investigate global expression patterns compared to differential display rt-pcr. although differential display rt-pcr can be labour-intensive, it has its own merits over those of dna microarray. while the latter usually consists of a well-defined set of species-specific genes, differential display rt-pcr allows the investigation of host-microbe interactions without bias towards any mrna transcripts. this means that the r ...201020300989
ev71: an emerging infectious disease vaccine target in the far east?hand, foot, and mouth disease (hfmd) is a common viral illness in infants and children caused by viruses that belong to the enterovirus genus of the picornavirus family. although most hfmd do not result in serious complications, outbreaks of hfmd caused by enterovirus 71 (ev71) can present with a high rate of neurological complications, including meningoencephalitis, pulmonary complications, and possibly death. hfmd caused by ev71 has become a major emerging infectious disease in asia and the hi ...201020304038
ev71 induces cox-2 expression via c-src/pdgfr/pi3k/akt/p42/p44 mapk/ap-1 and nf-kappab in rat brain astrocytes.enterovirus 71 (ev71) induces the expression of cyclooxgenase (cox)-2 served as a major neurotoxic factor in cns injury. however, the mechanisms underlying ev71-initiated intracellular signaling pathways leading to cox-2 expression remain unknown. therefore, we investigated the mechanisms underlying ev71-induced cox-2 expression and prostaglandin e(2) (pge(2)) production in rat brain astrocytes (rba)-1, determined by western blotting, rt-pcr, and promoter assay. here, we reported that ev71-induc ...201020333648
neural pathogenesis of enterovirus 71 infection.enterovirus 71 (ev71) is a neurotropic pathogen that can cause severe neural diseases and complications on infected patients. clinical observations showed that ev71-induced immune responses may be associated with virus induced neurogenic pulmonary edema. here reviewed studies that discovered several host molecules as potential factors for ev71 virulence.201020348010
circulating viruses associated with severe complicated enterovirus infection in taiwan: a multi-year analysis.few studies have investigated the viral isolation characteristics for severe complicated enterovirus infection (scei). this study evaluated the seasonality and contribution of circulated viruses to the chronologic trend and weekly reported scei epidemic.201020351529
evolutionary trajectory of the vp1 gene of human enterovirus 71 genogroup b and c viruses.from 1963 to 1986, human enterovirus 71 (hev71) infections in the netherlands were successively caused by viruses of subgenogroups b0, b1 and b2. a genogroup shift occurred in 1987, after which viruses of subgenogroups c1 and c2 were detected exclusively. this is in line with hev71 typing in australia, europe and the usa, but is distinct from that in the asian pacific region, where hev71 subgenogroups b3-b5 and c4-c5 have caused large outbreaks since 1997. to understand these observations in hev ...201020375223
sequence analysis of six enterovirus 71 strains with different virulences in humans.enterovirus 71 (ev71) infection is the main cause of hand, foot and mouth disease (hfmd) and has been associated with severe neurological diseases resulting in high mortalities. in this study, six ev71 strains isolated from patients with different clinical symptoms were sequenced and analyzed in a mouse model of ev71 infection. in a phylogenetic tree, based on the complete vp1 gene sequence, all six strains grouped into the c4 genotype. the sequence analysis revealed that there are nucleotide ch ...201020398708
enterovirus 71 vaccine: close but still far.enterovirus 71 (ev71), a member of the enterovirus genus of the picornaviridae family, is one of the causative pathogens of hand-foot-and-mouth disease (hfmd) and the most common etiological agent isolated from hfmd patients complicated with neurological disorders. ev71 has become an increasingly important neurotropic enterovirus in the post-poliomyelitis eradication era. effective antiviral agents and vaccines against this virus are currently still under development. we reviewed publications on ...201020400350
[etiology of hand, foot and mouth disease in guangzhou in 2008].to understand the etiology of hand, foot and mouth disease (hfmd) in guangzhou area in 2008.201020426938
[autopsy report of two cases with enterovirus type 71 infection brainstem encephalitis and literature review].to understand clinicopathologic characteristics of hand-foot-and-mouth disease.201020426961
an outbreak of enterovirus 71 in a nursery.in this article we report a nosocomial outbreak of enterovirus 71 (ev71) in a newborn nursery and describe the clinical presentations of infected infants. community outbreaks of ev71 are quite common in epidemic areas, but a nosocomial outbreak of ev71 is a rare occurrence. a total of 7 out of 19 infants (37%) had symptoms. all infants had poor activity, 6 (86%) had fever, 4 (57%) had drowsiness, 3 (43%) had diarrhoea, and 2 (29%) had oral ulcers. four infants (57%) suffered from encephalitis. t ...201020429712
[clinical characteristics and treatment assessments of severe enterovirus 71 infected children].to facilitate early recognition of ominous clinical manifestations, to understand pathophysiology and assess treatment effects in patients with severe enterovirus 71 (ev71) associated hand, foot and mouth disease (hfmd).201020441698
an emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of hand foot and mouth disease in fuyang city of china.hand, foot and mouth disease (hfmd), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. it can be caused by enteroviruses, particularly coxsackieviruses and human enterovirus 71 (hev71) with highly variable clinical manifestations. in the spring of 2008, a large, unprecedented hfmd outbreak in fuyang city of anhui province in the central part of southeastern china resulted in a high aggregation of fatal cases. in this study, ...201020459851
clinical and etiological characteristics of enterovirus 71-related diseases during a recent 2-year period in korea.human enterovirus 71 (ev 71) has caused large-scale outbreaks of hand-foot-and-mouth disease (hfmd), particularly in the asian-pacific region. in this study, we report a major outbreak of ev 71 infection in korea and describe the clinical differences between ev 71 and non-ev 71 enterovirus infections. we prospectively enrolled patients with suspected viral infections during a recent 2-year period through a nationwide surveillance system. we identified 719 patients with suspected hfmd or herpangi ...201020463159
monoclonal antibody induced with inactived ev71-hn2 virus protects mice against lethal ev71-hn2 virus infection.enterovirus 71 (ev71) is a viral pathogen that belongs to the picornaviridae family, ev71-infected children can develop severe neurological complications leading to rapid clinical deterioration and death.201020500892
phylogenetic evidence for a recent spread of two populations of human enterovirus 71 in european countries.human enterovirus 71 (ev-71) is a cause of seasonal epidemics of hand, foot and mouth disease, and of less common but severe neurological manifestations. uncertainty persists regarding the circulation of virus populations in several geographical areas and the timescale of their dissemination. we determined ev-71 sequences at loci 1d (vp1 capsid protein) and 3cd (non-structural proteins) in 86 strains recovered in austria, france and germany and performed an evolutionary genetic study of extant v ...201020505012
[genetic analysis of vp1 sequences of enterovirus 71 isolated from patients of hand, foot and mouth disease in beijing, 2008].to get genetic information of vp1 coding region of hev71 in beijing in 2008.200920518331
the 3c protein of enterovirus 71 inhibits retinoid acid-inducible gene i-mediated interferon regulatory factor 3 activation and type i interferon responses.enterovirus 71 (ev71) is a human pathogen that induces hand, foot, and mouth disease and fatal neurological diseases. immature or impaired immunity is thought to associate with increased morbidity and mortality. in a murine model, ev71 does not facilitate the production of type i interferon (ifn) that plays a critical role in the first-line defense against viral infection. administration of a neutralizing antibody to ifn-alpha/beta exacerbates the virus-induced disease. however, the molecular ev ...201020519382
producing infectious enterovirus type 71 in a rapid strategy.enterovirus 71 (ev71) is an etiologic agent of hand-foot-and-mouth disease (hfmd), and recent hfmd epidemics worldwide have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case-fatality rates. ev71 contains a positive-sense single-stranded genome rna of approximately 7400 bp in length which encodes a polyprotein with a single open reading frame (orf), which is flanked by untranslated regions at both the 5' and 3' ends.201020525351
an investigation of epidemic enterovirus 71 infection in taiwan, 2008: clinical, virologic, and serologic features.enterovirus 71 (ev71) is causing life-threatening hand-foot-mouth disease in asia. in taiwan, ev71 epidemics with different predominant genotypes occurred in 1998 (c2), 2000-2001 (b4), and 2004-2005 (c4). this genotype replacement may have important implications for vaccine development and prediction of epidemics. a nationwide ev71 outbreak occurred again in 2008, which provided a unique opportunity to characterize clinical, virologic, and serologic features of this epidemic.201020543760
emergence of enterovirus 71 "double-recombinant" strains belonging to a novel genotype d originating from southern china: first evidence for combination of intratypic and intertypic recombination events in ev71.hand-foot-mouth disease due to enterovirus 71 (ev71) and coxsackievirus a16 (ca16) has recently caused large outbreaks in mainland china in 2008. we performed complete genome sequencing on two ev71 (sz/hk08-5 and sz/hk08-6) and two ca16 (sz/hk08-3 and sz/hk08-7) strains from patients in shenzhen, china. phylogenetic, similarity plot and bootscan analyses revealed recombination between ev71 genotypes b and c at the 2a-2b junction, and between ev71 genotype b and ca16 strain g-10 in the 3c region ...201020549263
long persistence of ev71 specific nucleotides in respiratory and feces samples of the patients with hand-foot-mouth disease after recovery.ev71 is associated with the fatal cases of brain stem encephalitis during large hfmd outbreaks from 1998 to 2008. ev71 may continuously shed from upper respiratory tracts and feces of hfmd patients for relatively long time after recovery. however, the persistence of viruses in the patients' secretions and excretions is not clear.201020565813
[an analysis of the characteristics and etiology of hand, foot and mouth disease in a guangzhou sentinel hospital from may to december, 2008].to analyze the characteristics and etiology of hand, foot and mouth disease (hfmd) in a sentinel hospital of guangzhou.201020584671
the enterovirus 71 epidemic in 2008--public health implications for hong kong.we compared the epidemiological, clinical and laboratory characteristics of enterovirus 71 (ev71) cases recorded in the epidemic year of 2008 with those of the past decade.201020599410
high expression of vascular endothelial growth factor in ev71-infected patients does not originate from ev71-infected cells.enterovirus (ev) 71 is an important pathogen causing death in children under 5 years of age worldwide. however, the core pathogenesis remains elusive. we reveal that the protein expression level of vascular endothelial growth factor (vegf) in ev71 patients was 2-fold higher than in normal controls. however, the origin of vegf in ev71-infected patients remains unclear.201020606461
performance of detecting igm antibodies against enterovirus 71 for early diagnosis.enterovirus 71 (ev71) infection is more likely to induce severe complications and mortality than other enteroviruses. methods for detection of igm antibody against ev71 had been established for years, however, the performance of the methods in the very early diagnosis of ev71 infection had not been fully evaluated, which is especially meaningful because of the short incubation period of ev71 infection. in this report, the performance of an igm anti-ev71 assay was evaluated using acute sera colle ...201020613983
identification of micrornas involved in the host response to enterovirus 71 infection by a deep sequencing approach.role of microrna (mirna) has been highlighted in pathogen-host interactions recently. to identify cellular mirnas involved in the host response to enterovirus 71 (ev71) infection, we performed a comprehensive mirna profiling in ev71-infected hep2 cells through deep sequencing. 64 mirnas were found whose expression levels changed for more than 2-fold in response to ev71 infection. gene ontology analysis revealed that many of these mrnas play roles in neurological process, immune response, and cel ...201020625495
molecular characterization of enteroviruses detected in gyeong-ju and po-hang provinces of korea in 2003.we identified and characterized enteroviruses by amplifying the partial vp1 gene from pediatric patients with aseptic meningitis and other enterovirus-related diseases from the gyeong-ju and po-hang provinces of korea in 2003. we identified two strains each of coxsackievirus a (ca) 6, ca9, and ca10; three enterovirus 71 (ev71) strains; and six echovirus 30 (e30) strains. the three ev71 strains were characterized as genogroup c4. these results are the first documentation reporting the occurrence ...201020640907
development of polyclonal antisera to clone enterovirus 71 cellular receptor.enterovirus 71 (env71) is a member of picornaviridae family and was shown to be of public health concern in the far east because of the notorious outbreaks it caused, with novel clinical features in the affected patients. in this study we assessed the use of virus capsid protein vp1 in viral receptor research.201020644305
clinical and molecular characterization of hand-foot-and-mouth disease in thailand, 2008-2009.hand-foot-and-mouth disease (hfmd) is caused by a group of enteroviruses, most commonly coxsackievirus a 16 (ca16) and enterovirus 71 (ev71). in general, the disease is mild and self-limited except in the case of ev71 infections, which may incur serious complications. this research focused on virus characterization of hfmd cases in thailand from 2008-2009, related clinical findings and complications of specific enterovirus subtypes. specimens (stool, vesicle fluid, throat swab/sputum) from 48 ca ...201020657060
a bifunctional anti-enterovirus compound that inhibits replication and the early stage of enterovirus 71 infection.enviroxime is an anti-enterovirus compound that targets viral protein 3a and/or 3ab and suppresses a replication step of enterovirus by an unknown mechanism. to date, a number of anti-enterovirus compounds that have little structural similarity to enviroxime but induce common resistance mutations in the 3a-encoding region have been identified. the present study identified a novel type of functionally enviroxime-like compound, an-12-h5. this compound had no structural similarity to enviroxime or ...201020660150
enterovirus type 71 2a protease functions as a transcriptional activator in yeast.enterovirus type 71 (ev71) 2a protease exhibited strong transcriptional activity in yeast cells. the transcriptional activity of 2a protease was independent of its protease activity. ev71 2a protease retained its transcriptional activity after truncation of 40 amino acids at the n-terminus but lost this activity after truncation of 60 amino acids at the n-terminus or deletion of 20 amino acids at the c-terminus. thus, the acidic domain at the c-terminus of this protein is essential for its trans ...201020682079
enterovirus 71 infection of monocytes with antibody-dependent enhancement.enterovirus (ev) is an rna virus that has circulated with different serotypes and genotypes worldwide. enterovirus 71 (ev71) is a major neurotropic virus that causes severe brain stem encephalitis (be) in infants and young children. the most vulnerable age for fatal infection is 6 to 11 months. this is associated with the coincident decline in maternal antibodies. the current report describes our finding that ev71 can infect human peripheral blood monocytes. we were able to show that ev71 infect ...201020685937
[detection and analysis of the enterovirus infection within 159 cases of hand-foot-mouth disease by a real-time reverse transcription-pcr assay].to reveal the enterovirus infection within children suffering hand-foot-mouth disease (hfmd) in the capital institute of pediatrics from aprial to august, 2009, for the sake of clinical diagnosis and treatment.200920718366
epidemiology of hand, foot, and mouth disease and genotype characterization of enterovirus 71 in jiangsu, china.in the spring of 2008, an ev71-caused hand, foot, and mouth disease (hfmd) outbreak occurred in fuyang city, anhui province, china. jiangsu province that borders auhui to the east is presumed as a key station for the spread of ev71 to other regions of the yangtze river delta.201020719557
methylene blue-mediated photodynamic inactivation as a novel disinfectant of enterovirus 71.we tested whether methylene blue, an inexpensive and safe photosensitizer, is feasible for photodynamic inactivation of enterovirus 71 (ev71) in the environment.201020719762
enterovirus 71 virus-like particle vaccine: improved production conditions for enhanced yield.to develop the enterovirus 71 (ev71) vaccine, we previously constructed a recombinant baculovirus (bac-p1-3cd) co-expressing ev71 p1 (under polyhedrin promoter) and 3cd (under p10 promoter) proteins, which caused p1 cleavage by 3cd protease and self-assembly of virus-like particles (vlps) in sf-9 cells. assuming that reducing the 3cd expression can alleviate the competition with p1 expression and elevate the vlps yield, hereby we constructed bac-p1-c3cd and bac-p1-i3cd expressing 3cd under weake ...201020797455
dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus a16 in infants.enterovirus 71 (ev71) and coxsackievirus a16 (cox a16) are major causative agents for hand, foot and mouth disease (hfmd). studies indicate that the frequent hfmd outbreaks result in a few hundreds children's death in china in recent years. the vaccine and other research for hfmd need to be developed urgently. the aims of our study were: to explore dynamic development of mother-source neutralizing antibodies against ev71 and cox a16 in infants from jiangsu province, china, and to provide the fun ...201020819628
fulminant enterovirus 71 infection: case report.a previously healthy 3-year-old boy presented with high-grade fever, dyspnoea, alteration of consciousness, tachycardia and shock. a few erythematous macules and papules were seen on his palms and soles. echocardiogram showed poor left ventricular contraction. cardiac enzymes and pro-b-type natriuretic peptide were elevated. milrinone, low-dose dopamine and intravenous immunoglobulin were administered. the patient recovered after 5 days without cardiac or neurological sequelae. the serological r ...201020828460
combined peptides of human enterovirus 71 protect against virus infection in mice.human enterovirus 71 (ev71) is a cause of hand, foot and mouth disease (hmfd) in children under 6 years old, and could cause serious neurological complications in some patients. numerous large outbreaks of ev71 caused hmfd have occurred recently in asia, especially in china. the cross-reactivity of ev71 with human brain tissue was observed and the cross-reactivity inducing regions were identified in previously study, which suggested that there were two regions in structural proteins of virus sho ...201020831911
[an overview of the evolution of ev71 vaccine].ev71 infection has become a serious public health threat especially among young children. yet, at present, no specific antiviral drug against ev71 infection is available. a number of scientists are studying various kinds of vaccines, including inactivated vaccine, virus-like particle vaccine, dna vaccine, synthetic peptide vaccines, and transgenic oral vaccine. this article reviews the recent advancement in the design of various kinds of vaccine against ev71 as well as their prospective usefulne ...201020842875
[the lost decade of global polio eradication and moving forward].the global polio eradication initiative was aimed to eradicate poliomyelitis by the year 2000, however, polio eradication is still not in sight even in 2010, over 10 years after the initial target date. in 2010, indigenous transmission of wild polioviruses has been interrupted throughout the world except four countries, afghanistan, pakistan, india, and nigeria. despite the intense use of monovalent oral polio vaccines, type 1 and type 3 wild polioviruses still circulate in the four remaining po ...201020848864
forecasting the economic value of an enterovirus 71 (ev71) vaccine.enterovirus 71 (ev71) is a growing public health concern, especially in asia. a surge of ev71 cases in 2008 prompted authorities in china to go on national alert. while there is currently no treatment for ev71 infections, vaccines are under development. we developed a computer simulation model to determine the potential economic value of an ev71 vaccine for children (<5 years old) in china. our results suggest that routine vaccination in china (ev71 infection incidence ≈0.04%) may be cost-effect ...201020923711
passive protection effect of chicken egg yolk immunoglobulins on enterovirus 71 infected mice.the objective of this study is to evaluate the passive protective efficiency of immunoglobulin in yolk (igy) specific against human enterovirus type 71 (ev71). the antibody was raised by intramuscular immunization to 10 white leghorn hens, with inactivated human ev71 serving as the antigen. the titer and specificity of the antibody were analyzed from purified igy in the egg yolks of immunized hens. results indicate that the titer of igy specific against ev71 increased from the third week after t ...201020937321
adaptive mutations in the genomes of enterovirus 71 strains following infection of mouse cells expressing human p-selectin glycoprotein ligand-1.we recently identified human p-selectin glycoprotein ligand-1 (psgl-1) as a functional enterovirus 71 (ev71) receptor and demonstrated psgl-1-dependent replication for some ev71 strains in human leukocytes. here, we report that four out of five psgl-1-binding strains of ev71 replicated poorly in mouse l929 cells stably expressing human psgl-1 (l-psgl-1 cells). therefore, we compared the replication kinetics and entire genomic sequence of five original ev71 strains and the corresponding ev71 vari ...201020943886
significant elevation of b cells at the acute stage in enterovirus 71-infected children with central nervous system involvement.a feature of the large outbreak of human enterovirus 71 (ev71)-associated hand-foot-and-mouth (hfmd) disease in china in 2008 was that severe cases presented with encephalitis. this study was performed to evaluate the immunophenotypic characteristics of patients with neurological involvement. twenty-one patients with encephalitis and 14 with uncomplicated hfmd were recruited. age-matched healthy volunteers were enrolled as controls. peripheral lymphocyte subsets were analyzed by use of 3-colour ...201020950217
the largest outbreak of hand; foot and mouth disease in singapore in 2008: the role of enterovirus 71 and coxsackievirus a strains.during 2008, singapore experienced its largest ever outbreak of hand, foot and mouth disease (hfmd), resulting in 29686 cases, including four cases of encephalitis and one fatality.201020952237
the essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71.little is currently known about the infectious entry process of human enterovirus 71 (hev71) into host cells, which may represent potential anti-viral targeting sites. in this study a targeted small-interfering rna (sirna) screening platform assay was established and validated to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics, and endosomal trafficking essential for hev71 infection. screen evaluation was conducted via the expression of well ch ...201020956521
genetic diversity and c2-like subgenogroup strains of enterovirus 71, taiwan, 2008.human enterovirus 71 (ev-71) is known of having caused numerous outbreaks of hand-foot-mouth disease, and other clinical manifestations globally. in 2008, 989 ev-71 strains were isolated in taiwan.201020959020
strategies for antiviral screening targeting early steps of virus infection.viral infection begins with the entry of the virus into the host target cell and initiates replication. for this reason, the virus entry machinery is an excellent target for antiviral therapeutics. in general, a virus life cycle includes several major steps: cell-surface attachment, entry, replication, assembly, and egress, while some viruses involve another stage called latency. the early steps of the virus life cycle include virus attachment, receptor binding, and entry. these steps involve th ...201020960301
a comparison of the biological characteristics of ev71 c4 subtypes from different epidemic strains.the comparative analysis of the biological characterization and the genetic background study of ev71 circulating strains is commonly recognized as basic work necessary for development of an effective ev71 vaccine. in this study, we sequenced five ev71 circulating strains, isolated from fuyang, hefei, kunming and shenzhen city of china and named them fy-23, fy-22, h44, k9 and s1 respectively. the sequence alignment demonstrated their genotypes be c4. the genetic distance of the vp1 gene from thes ...201020960306
virology, epidemiology, pathogenesis, and control of enterovirus 71.first isolated in california, usa, in 1969, enterovirus 71 (ev71) is a major public health issue across the asia-pacific region and beyond. the virus, which is closely related to polioviruses, mostly affects children and causes hand, foot, and mouth disease with neurological and systemic complications. specific receptors for this virus are found on white blood cells, cells in the respiratory and gastrointestinal tract, and dendritic cells. being an rna virus, ev71 lacks a proofreading mechanism ...201020961813
clinical features, diagnosis, and management of enterovirus 71.although poliomyelitis has been mostly eradicated worldwide, large outbreaks of the related enterovirus 71 have been seen in asia-pacific countries in the past 10 years. this virus mostly affects children, manifesting as hand, foot, and mouth disease, aseptic meningitis, poliomyelitis-like acute flaccid paralysis, brainstem encephalitis, and other severe systemic disorders, including especially pulmonary oedema and cardiorespiratory collapse. clinical predictors of severe disease include high te ...201020965438
developments towards antiviral therapies against enterovirus 71.enterovirus 71 (ev71) has emerged as a clinically important neurotropic virus that can cause acute flaccid paralysis and encephalitis, leading to cardiopulmonary failure and death. recurring outbreaks of ev71 have been reported in several countries. the current lack of approved anti-ev71 therapy has prompted intense research into antiviral development. several strategies--ranging from target-based chemical design to compound library screenings--have been employed, while others revisited compound ...201020974282
enterovirus 71 infection with central nervous system involvement, south korea.we assessed neurologic sequelae associated with an enterovirus 71 (ev71) outbreak in south korea during 2009. four of 94 patients had high signal intensities at brainstem or cerebellum on magnetic resonance imaging. two patients died of cardiopulmonary collapse; 2 had severe neurologic sequelae. severity and case-fatality rates may differ by ev71 genotype or subgenotype.201021029539
epidemiology of human enterovirus 71 infections in france, 2000-2009.human enterovirus 71 (ev-71) emerged as a significant pathogen able to cause large outbreaks involving severe neurological cases and children fatalities in asia.201021035387
retrospective seroepidemiology indicated that human enterovirus 71 and coxsackievirus a16 circulated wildly in central and southern china before large-scale outbreaks from 2008.large nationwide outbreaks of hand, foot, and mouth disease (hfmd) occurred in china from 2008; most of the cases were in children under 5 years. this study aims to identify the situation of natural human enterovirus 71 (hev71) and coxsackievirus a16 (cva16) infections in children before 2008 in china.201021050463
application of a molecular method for the classification of human enteroviruses and its correlation with clinical manifestations.a new molecular classification scheme has recently been adopted that groups all enteroviruses into four species, designated human enterovirus a (hev-a) through d. in this study, we tried to demonstrate the correlation between this molecular classification scheme and clinical manifestations in patients.201021075700
tyrosine sulfation of the amino terminus of psgl-1 is critical for enterovirus 71 infection.enterovirus 71 (ev71) is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, ev71 has been also associated with various neurological diseases including fatal cases in large ev71 outbreaks particularly in the asia pacific region. recently we identified human p-selectin glycoprotein ligand-1 (psgl-1) as a cellular receptor for entry and replication of ev71 in leukocytes. psgl-1 is a sialomucin expressed on the surface of leukocytes, se ...201021079683
novel multiplex oligonucleotide-conjugated bead suspension array for rapid identification of enterovirus 71 subgenogroups.a high-throughput multiplex bead suspension array was developed for the rapid subgenogrouping of ev71 strains, based on single nucleotide polymorphisms observed within the vp1 region with a high sensitivity as low as 1 pfu. of 33 viral isolates and 55 clinical samples, all ev71 strains were successfully detected and correctly subgenogrouped.201021084510
ev71 viral secretion by symptomatic hand foot and mouth disease patients and their asymptomatic close contacts. 201021087628
molecular characterization of enterovirus 71 and coxsackievirus a16 using the 5' untranslated region and vp1 region.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are members of the species human enterovirus a, and are both major and independent aetiological agents of hand-foot-and-mouth disease. the human enterovirus (hev) 5' untranslated region (utr) is fundamentally important for efficient virus replication and for virulence, whilst the vp1 region correlates well with antigenic typing by neutralization, and can be used for virus identification and evolutionary studies. a comparison was undertaken of ...201021148280
optimized development of a candidate strain of inactivated ev71 vaccine and analysis of its immunogenicity in rhesus monkeys.enterovirus type 71 (ev71) is one of the main etiologic agents responsible for periodic epidemics of hand-foot-and-mouth disease (hfmd). the prevention and control of ev71 epidemics with effective anti-viral agents and vaccines is very important for public health. because the pathogenesis of ev71 in the human body is not completely clear and genetic variations in the virus during its replication are difficult to control, we have focused on the development of an inactivated whole-virus vaccine. i ...201021150270
development and evaluation of a reverse transcription-loop-mediated isothermal amplification assay for rapid detection of enterovirus 71.human enterovirus 71 (ev71) is the major etiological agent of hand, foot, and mouth disease (hfmd), which is a common infectious disease in young children and infants. ev71 can cause various clinical manifestations and has been associated with severe neurological complications; it has resulted in fatalities during recent outbreaks in asian-pacific regions since 1997. the early and rapid detection is critical for prevention and control of ev71 infection, since no vaccine or antiviral drugs are cu ...201021177907
structures of ev71 rna-dependent rna polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in china.enterovirus 71 (ev71), one of the major causative agents for hand-foot-and-mouth disease (hfmd), has caused more than 100 deaths among chinese children since march 2008. the ev71 genome encodes an rnadependent rna polymerase (rdrp), denoted 3d(pol), which is central for viral genome replication and is a key target for the discovery of specific antiviral therapeutics. here we report the crystal structures of ev71 rdrp (3d(pol)) and in complex with substrate guanosine-5'-triphosphate and analog 5- ...201021203964
[progress in the pathogenesis of ev71 infection]. 201021215185
biochemical characterization of enterovirus 71 3d rna polymerase.an unusual enterovirus 71 (ev71) epidemic has begun in china since 2008. ev71 rna polymerases (3d(pol)) showed polymerase activity with an mn(2+). little activity was detected with co(2+), and no activity was detected with mg(2+), ca(2+), cu(2+), ni(2+), cd(2+), or zn(2+). it is a primer-dependent polymerase, and the enzyme functioned with both di- and 10-nucleotide rna primers. dna primer, dt15, increased primer activity, similar to other enterovirus 3d(pol). however, ev71 3d(pol) initiated de ...201121220056
evaluation of enterovirus 71 immune status in são paulo state, brazil.antibodies to enterovirus 71 (ev71) were evaluated in são paulo state during 1999-2005. the titer of neutralizing antibodies against ev71 was determined by microneutralization assay, and a titer of ≥ 1:8 was defined as indicative of protected immunity. neutralizing antibodies to ev71 were observed in 12.4% (55/442) of sera samples, a low protective rate, suggesting that ev71 infection is uncommon in this region, but that there is a relatively high susceptibility to ev71 related diseases, which i ...201021225219
sustained high levels of interleukin-6 contribute to the pathogenesis of enterovirus 71 in a neonate mouse model.enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd) in young children and has been consistently associated with the most severe complications of the disease, including central nervous system inflammation and pulmonary edema. increasing frequency and amplitude of ev71 outbreaks have raised awareness and concerns worldwide. previous reports proposed that overwhelming virus replication combined with the induction of massive proinflammatory cytokines is respons ...201121228224
oncolysis of malignant human melanoma tumors by coxsackieviruses a13, a15 and a18.many rna viruses are displaying great promise in the field of oncolytic virotherapy. previously, we reported that the picornavirus coxsackievirus a21 (cva21) possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. in the present study, we demonstrate that three additional group a coxsackieviruses; coxsackievirus a13 (cva13), coxsackievirus a15 (cva15) and coxsackievirus a18 (cva18), also have similar oncolytic activity against malignant mela ...201121241513
neonatal rhesus monkey is a potential animal model for studying pathogenesis of ev71 infection.data from limited autopsies of human patients demonstrate that pathological changes in ev71-infected fatal cases are principally characterized by clear inflammatory lesions in different parts of the cns; nearly identical changes were found in murine, cynomolgus and rhesus monkey studies which provide evidence of using animal models to investigate the mechanisms of ev71 pathogenesis. our work uses neonatal rhesus monkeys to investigate a possible model of ev71 pathogenesis and concludes that this ...201121262515
an enterovirus 71 epidemic in guangdong province of china, 2008: epidemiological, clinical, and virogenic manifestations.enterovirus 71 (ev71) is shown to be a major causative agent in outbreaks of hand, foot, and mouth disease (hfmd) reported in guangdong (gd) province of china in 2008. a total of 48,876 hfmd cases (131 severe and 21 fatal) were reported to the gd hfmd web-based surveillance system, which covers 871 clinics. the main causes of death included central nervous system damage, heart failure, and pulmonary edema. the incidence rate was 52 per 100,000, and the epidemic peak appeared in may and june. ev7 ...201121266750
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