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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
human enterovirus 71 and hand, foot and mouth disease.hand, foot and mouth disease (hfmd) is generally a benign febrile exanthematous childhood disease caused by human enteroviruses. the route of transmission is postulated to be faeco-oral in developing areas but attributed more to respiratory droplet in developed areas. transmission is facilitated by the prolonged environmental survival of these viruses and their greater resistance to biocides. serious outbreaks with neurological and cardiopulmonary complications caused by human enterovirus 71 (he ...201020056019
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
introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3d polymerase.in 1998, an enterovirus 71 (ev71) epidemic in taiwan resulted in 78 deaths; however, the molecular basis of ev71 pathogenicity remains poorly understood. comparison of the deduced amino acid sequences in 3d polymerases of ev71clinical isolates showed the t251v or t251i substitution from 1986 and 1998 outbreaks. an ev71 replicon system showed that introducing an i251t mutation did not affect luciferase activities at 35 degrees c when compared with wild type; however, lower luciferase activities w ...201019906393
formaldehyde-inactivated whole-virus vaccine protects a murine model of enterovirus 71 encephalomyelitis against disease.enterovirus 71 (ev71) causes childhood hand, foot, and mouth disease and neurological complications, and no vaccines or therapeutic drugs are currently available. formaldehyde-inactivated whole-virus vaccines derived from ev71 clinical isolates and a mouse-adapted virus (mav) were tested in a mouse model of ev71 encephalomyelitis. after only two immunizations, given to mice at 1 and 7 days of age, the mav vaccine protected mice at 14 days of age from disease. tissues from immunized mice were neg ...201019864378
presence of high-titer neutralizing antibodies against enterovirus 71 in intravenous immunoglobulin manufactured from chinese donors. 201020001529
emergence and re-emergence of viral diseases of the central nervous system.neurologic disease is a major cause of disability in resource-poor countries and a substantial portion of this disease is due to infections of the cns. a wide variety of emerging and re-emerging viruses contribute to this disease burden. new emerging infections are commonly due to rna viruses that have expanded their geographic range, spread from animal reservoirs or acquired new neurovirulence properties. mosquito-borne viruses with expanding ranges include west nile virus, japanese encephaliti ...201020004230
extracorporeal life support for treatment of children with enterovirus 71 infection-related cardiopulmonary failure.enterovirus 71 (ev71) infection leading to cardiopulmonary failure (cpf) is rare, but usually fatal. in such cases, intensive cardiorespiratory support is essential for survival. in this study, we report our experience in the treatment of ev71-related cpf with extracorporeal life support (ecls).201020033668
development of a high-throughput assay for measuring serum neutralizing antibody against enterovirus 71.enterovirus 71 (ev71) is the main etiologic agent of hand, foot, and mouth disease (hfmd) and causes frequently severe neurological complications and mortality in young children. the serum neutralizing antibody response is the major indicator of ev71 infection and protective immunity. the current serum neutralization test based on inhibition of cytopathic effect (nt-cpe) requires manual microscopic examination, which is time-consuming and labor-intensive. in this study, a high-throughput neutral ...201020036286
detection of non-polio enteroviruses in hungary 2000-2008 and molecular epidemiology of enterovirus 71, coxsackievirus a16, and echovirus 30.human enteroviruses are associated with various clinical syndromes from minor febrile illness to severe, potentially fatal conditions like aseptic meningitis, paralysis, myocarditis, and neonatal enteroviral sepsis. between june 2000 and august 2008 echovirus (e) type 2, 4, 6, 7, 9, 11, 13, 25, 30, coxsackievirus (cv) -a16, -a19, -b5, and enterovirus 71 (ev71) were reported in hungary. in this study, 29 previously enterovirus positive samples from 28 patients diagnosed with hand, foot and mouth ...201020044791
enterovirus 71 induces cox-2 expression via mapks, nf-kappab, and ap-1 in sk-n-sh cells: role of pge(2) in viral replication.the enterovirus 71 (ev71) causes severe neurological diseases that were mediated through cyclooxygenase-2 (cox-2) expression in brain. however, the mechanisms underlying ev71-initiated intracellular signaling pathways leading to cox-2 expression remain unknown in neurons. here we report that exposure of sk-n-sh cells to ev71 increased cox-2 expression and pge(2) generation in a time- and virus titer-dependent manner, revealed by western blot, real-time pcr, and pge(2) analyses. these ev71-induce ...201019800403
risk factors for severe hand foot and mouth disease.hand foot and mouth disease (hfmd) and herpangina are enteroviral infectious diseases caused mainly by coxsackie virus a (ca) or enterovirus 71 (ev71). from 2000 to 2002, many complicated cases were reported in japan, therefore a nationwide questionnaire survey was carried out to assess the situation. the subjects were patients with hfmd or herpangina, or other enterovirus infection from 2000 to 2002, who were either hospitalized over 24 h or who died. the response rates were 41.3% in 2000 and 2 ...201019663940
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
echoviruses are a major cause of aseptic meningitis in infants and young children in kuwait.the etiologic agents of aseptic meningitis (am) often include human enteroviruses. the role of enteroviruses causing am in young children was investigated during a 3-year period in kuwait.201020846386
development of a multiplex polymerase chain reaction assay for simultaneous identification of human enterovirus 71 and coxsackievirus a16.human enterovirus 71 (hev71) and coxsackievirus a16 (cva16) are two major aetiological agents of hand, foot and mouth disease (hfmd) in children. recently there have been several large outbreaks of hfmd in vietnam and the asia-pacific region. in this study, a multiplex rt-pcr assay was developed in order to detect simultaneously hev71, cva16 and other human enteroviruses. enterovirus detection was performed with a mixture of three pairs of oligonucleotide primers: one pair of published primers f ...201020863857
inferring nonneutral evolution from contrasting patterns of polymorphisms and divergences in different protein coding regions of enterovirus 71 circulating in taiwan during 1998-2003.enterovirus (ev) 71 is one of the common causative agents for hand, foot, and, mouth disease (hfmd). in recent years, the virus caused several outbreaks with high numbers of deaths and severe neurological complications. despite the importance of these epidemics, several aspects of the evolutionary and epidemiological dynamics, including viral nucleotide variations within and between different outbreaks, rates of change in immune-related structural regions vs. non-structural regions, and forces d ...201020868512
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
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
[analysis of the epidemic characteristics of the etiological agents in children with hand, foot and mouth disease and its clinical significance].to investigate the epidemic characteristics of etiological agents in children with hand, foot and mouth disease (hfmd) and analyze the differences between the severe and mild cases with hfmd seen from 2008 to 2009 in the children's hospital.201021055092
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
changing epidemiology of hand, foot, and mouth disease in hong kong, 2001-2009.we report the surveillance findings of hand, foot, and mouth disease (hfmd) collected from a general practitioner-based sentinel surveillance system and outbreaks reported by institutions and a laboratory-based enterovirus surveillance system in hong kong from 2001 to 2009. a seasonal peak was detected in the warmer months (may-july), along with a smaller winter peak (october-december) from 2006 onwards. the number of older children (>5 years) infected increased from 25.4% in 2001 to 33.0% in 20 ...201021099093
[analyze the antibody level of enterovirus 71 about children cases of hand-foot-mouse disease outbreak].to analyze the enterovirus 71 infectious status about probably cases of hand-foot-mouse disease (hfmd).201021110438
comparison of reverse transcription loop-mediated isothermal amplification, conventional pcr and real-time pcr assays for japanese encephalitis virus.we developed and evaluated a reverse transcription loop-mediated isothermal amplification (rt-lamp) assay for detecting japanese encephalitis virus (jev). the sensitivity of the jev rt-lamp assay was in concordance with that of real-time rt-pcr and 10-fold more sensitive than that of conventional rt-pcr, which the detection limit was 24 copies/μl. the jev rt-lamp was highly specific, which no cross-reactivity was found with dengue-2 virus, rabies virus, norovirus, astrovirus and human enteroviru ...201021116858
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
simultaneous detection of enteroviruses from surface waters by real-time rt-pcr with universal primers.in order to realize simultaneous quantitative detection of various enteroviruses from water samples, a real-time reverse transcription-polymerase chain reaction (real-time rt-pcr) method was developed with universal primer pairs designed based on the highly conserved non-coding region sequences of genome targeting poliovirus, coxsackievirus and enterovirus 71. the recombinant plasmid was constructed as enterovirus dna standard by cloning poliovirus cdna into a pmd18-t vector. the real-time rt-pc ...201021179967
enterovirus 71 infection: an experience in korea, 2009.enterovirus 71 (ev71) has been recognized as a frequent cause of epidemics of hand-foot-and-mouth disease (hfmd) associated with severe neurological symptoms. in the spring of 2009, hfmd was epidemic in korea. severe cases with complication, including death, have been reported and it has become a public health issue. most symptomatic ev71 infections commonly result in hfmd or herpangina. these clinical manifestations can be associated with neurologic syndromes frequently. neurologic syndromes ob ...201021189926
enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in korea, 2009.hand-foot-mouth disease (hfmd) is a common viral illness in children, which is usually mild and self-limiting. however, in recent epidemics of hfmd in asia, enterovirus 71 (ev71) has been recognized as a causative agent with severe neurological symptoms with or without cardiopulmonary involvement. hfmd was epidemic in korea in the spring of 2009. severe cases with complications including death have been reported. the clinical characteristics in children with neurologic manifestations of ev71 wer ...201021189930
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
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
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
[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
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
broad reactive monoclonal antibodies for rapid identification of enteroviruses show cross-reactivity with chikungunya virus infected cells.in the past decade, enterovirus 71 (ev71) and chikungunya (chik) virus have re-emerged periodically causing serious public health problems in malaysia, since their first emergence in 1997 and 1998 respectively. this study demonstrates that chik virus causes similar patterns of cytopathic effect in cultured vero cells as some enteroviruses. they also show positive cross-reaction on direct immunofluorescence staining using monoclonal antibodies meant for typing enteroviruses. without adequate clin ...201020614726
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
emerging epidemic viral encephalitides with a special focus on henipaviruses.in the last few decades, there is an increasing emergence and re-emergence of viruses, such as west nile virus, enterovirus 71 and henipaviruses that cause epidemic viral encephalitis and other central nervous system (cns) manifestations. the mortality and morbidity associated with these outbreaks are significant and frequently severe. while aspects of epidemiology, basic virology, etc., may be known, the pathology and pathogenesis are often less so, partly due to a lack of interest among pathol ...201020652579
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
[antiviral activities of cycloheximide and its derivatives].cycloheximide (chx) inhibits protein synthesis in most eukaryotic cells and it is a well-known tool commonly used in biochemical research. in this paper, the antiviral spectrum of chx against several dna and rna viruses have been evaluated. chx showed strong inhibitory activities against several rna viruses such as hiv-1, influenza viruses, coxsackie b virus, enterovirus (ev71) and several dna viruses such as hsv and hcmv. especially the strong inhibitory activities of chx against coxsackie b vi ...201021351439
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
[rt-pcr identification and genetic characterizations of vp1 region of human enterovirus 71 isolated in beijing in 2008].to study the genetic characterizations of vp1 region of human enterovirus 71 (hev71) isolated from clinical specimens of hand, foot and mouth disease (hfmd) patients in beijing in 2008.201021604564
[human enterovirus 71 that firstly isolated in qinghai province and their genetic features of vp1 region].to study the genetic characterizations of vp1 gene of human enterovirus 71 (hev71) isolated from clinical specimens of hand, foot and mouth disease (hfmd) patients in qinghai province in 2008.201021604569
clinical characteristics and treatment of severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71 in china.hand-foot-mouth disease has become a major public health issue in children in china. in the present prospective study we investigated the clinical characteristics and emergency management of children with severe encephalitis associated with npe caused by enterovirus 71.201025214951
kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (ires) activity through fubp and hnrp proteins.flavonoids are associated with multiple biological and pharmacological activities, including anti-enterovirus activity. an internal ribosomal entry site (ires) required for viral protein translation is a potential drug target for enterovirus 71 (ev71). regulation translation initiation requires the interaction of ires specific trans-acting host factors with viral ires element. by evaluation of 12 flavonoids against ev71 infection, we found that (a) 7,8-dihydroxyflavone, kaempferol, quercetin, he ...201125212137
in vitro and in vivo characterization of a new enterovirus type 71-specific human intravenous immunoglobulin manufactured from selected plasma donors.background: enterovirus type 71 (ev71) causes large outbreaks with significant mortality among young children, and no specific antiviral treatment is currently available. antibody-based therapy represents a promising alternative strategy for lethal ev71 infection. our previous data has shown that anti-ev71 neutralization antibodies were present in a significant proportion of blood donors in china. objectives: to produce a new human intravenous immunoglobulin (ivig) product containing high titer ...201121641277
the virology and developments toward control of human enterovirus 71.enterovirus 71 (ev71), a member of the enterovirus genus in the picornaviridae family, was first recognized as a dermotrophic virus that usually cause mild, self-limiting hand-foot-and-mouth disease (hfmd). however, ev71 infection can sometimes induce a variety of severe neurological complications and even death. current large outbreaks of ev71 make this virus being a major public health issue. intense effort has been made to address its underlying pathogenesis and to develop effective means for ...201121651436
epidemics of enterovirus infection in chungnam korea, 2008 and 2009.abstract: previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in chungnam, korea from 2005 to 2006. the present study extended these observations to 2008 and 2009. in this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. the most prevalent month was july: 42.9% in 2008 and 31.9% in 2009. the highest rate of enterovirus-positive samples occurred in children < 1-year- ...201121668960
crystal structures of enterovirus 71 3c protease complexed with rupintrivir reveal the roles of the catalytically important residues.ev71 is the primary pathogen causing hfmd, however, the effective antiviral drug is currently unavailable. rupintrivir, an inhibitor against hrv, has potent antiviral activities against ev71. we determined high-resolution crystal structures of ev71 3c(pro)/rupintrivir complex, showing that although rupintrivir interacts with ev71 3c(pro) similarly as with hrv 3c(pro), the c-terminal of the inhibitor cannot accommodate in the leaving group pockets of ev71 3c(pro). our structures reveal that ev71 ...201121813612
enterovirus 71 2c protein inhibits tnf-{alpha}-mediated activation of nf-{kappa}b by suppressing i{kappa}b kinase {beta} phosphorylation.enterovirus 71 (ev71), a single, positive-stranded rna virus, has been regarded as the most important neurotropic enterovirus after the eradication of the poliovirus. ev71 infection can cause hand, foot, and mouth disease or herpangina. cytokine storm with elevated levels of proinflammatory and inflammatory cytokines, including tnf-α, has been proposed to explain the pathogenesis of ev71-induced disease. tnf-α-mediated nf-κb signaling pathway plays a key role in inflammatory response. we hypothe ...201121810613
molecular detection and identification of enteroviruses in children admitted to a university hospital in greece.although enteroviral infections occur frequently during childhood, the circulation of particular serotypes has never been studied in greece. the objectives of the present report were molecular detection and identification of human enteroviruses in children admitted with nonspecific febrile illness or meningitis to a university hospital during a 22-month period. a one-step real-time rt-pcr protocol was used for rapid enterovirus detection in genetic material extracted directly from clinical sampl ...201121803150
circulating coxsackievirus a16 identified as recombinant type a human enterovirus, china.to determine the relationship of coxsackievirus a16 (ca16) to prototype ca16-g10, we conducted a phylogenetic analysis of circulating ca16 strains in china. complex recombinant forms of ca16-related viruses involving multiple human enteroviruses, subgroup a (ca4, ca16, and enterovirus 71), are prevalent among patients with hand, foot, and mouth disease.201121801645
enterovirus 71 and coxsackievirus a16 3c proteases: binding to rupintrivir and their substrate, and anti-hfmd drug design.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hand foot and mouth disease (hfmd) which is prevalent in asia. thus far there are no prophylactic or therapeutic measures against hfmd. the 3c proteases from ev71 and cva16 play important roles in viral replication and are therefore ideal drug targets. by using biochemical, mutational and structural approaches, we broadly characterized both proteases. a series of high-resolution structures of the free or subst ...201121795339
[the genetical evolution of the full length genes of 5 ev 71 strains from 5 shenzhen patients with hand-food-mouth disease associated with ev71 infection].to investigate the characteristics of molecular epidemiology and molecular evolution of 5 ev 71 (enterovirus 71, ev71) strains from 5 shenzhen patients with hand-food-mouth disease associated with ev 71 infection.201121789856
[enterovirus 71 induces apoptosis in a bax dependent manner].to explore the molecular mechanism of apoptosis induced by enterovirus 71 (ev71) infection.201121789855
sumoylation-promoted enterovirus 71 3c degradation correlates with a reduction in viral replication and cell apoptosis.enterovirus (ev) 71, a member of the picornaviridae family, may cause serious clinical manifestations associated with the central nervous system. enterovirus 3c protease is required for virus replication and can trigger host cell apoptosis via cleaving viral polyprotein precursor and cellular proteins, respectively. while the role of the 3c protease in processing viral and cellular proteins has been established, very little is known about the modulation of ev71 3c function by host cellular facto ...201121784861
[seroepidemiology investigation of neutralizing antibody against enterovirus 71 among healthy people in tianjin].to investigate the latent infection caused by enterovirus 71 (ev71) among healthy people in tianjin and to provide evidence on prevention and control hand-food and mouth diseases (hfmd).201121781473
[progress in research on enterovirus type 71]. 201121774260
[sequence and antigenicity analysis for vp4s of ev71 strains isolated from children in beijing].in order to learn about the correlation between the sequences of vp4 of ev71 and clinical symptoms of patients and analyze the antigenicity of vp4 of ev71, as well as the cross-reactivity with vp4 of ca16, the sequences of vp4 gene from 10 ev71 strains isolated from infants and children with hand, foot and mouth diseases (hfmd) during 2007 to 2009 were determined through standard molecular cloning protocols, and the results were analyzed by editseq and megalign of dnastar. full-length genes of v ...201121774244
development and evaluation of reverse transcription-loop-mediated isothermal amplification assay for rapid detection of enterovirus 71.abstract: background: hand, foot, and mouth disease (hfmd) caused by enterovirus 71 (ev71) is very common in china. it is difficult to distinguish between ev71 and coxsackievirus a16 (cva16) infections in clinical hfmd patients. routine laboratory diagnosis of ev71 infection is time-consuming and requires expensive instruments. in this study, we have developed a one-step, single tube, reverse transcription-loop-mediated isothermal amplification (rt-lamp) assay for rapid and sensitive detection o ...201121767352
the seroprevalence and seroincidence of enterovirus71 infection in infants and children in ho chi minh city, viet nam.enterovirus 71 (ev71)-associated hand, foot and mouth disease has emerged as a serious public health problem in south east asia over the last decade. to better understand the prevalence of ev71 infection, we determined ev71 seroprevalence and seroincidence amongst healthy infants and children in ho chi minh city, viet nam. in a cohort of 200 newborns, 55% of cord blood samples contained ev71 neutralizing antibodies and these decayed to undetectable levels by 6 months of age in 98% of infants. th ...201121765891
display of vp1 on the surface of baculovirus and its immunogenicity against heterologous human enterovirus 71 strains in mice.human enterovirus 71 (ev71) is a common cause of hand, foot and mouth disease (hfmd) in young children. it is often associated with severe neurological diseases and has caused high mortalities in recent outbreaks across the asia pacific region. currently, there is no effective vaccine and antiviral agents available against ev71 infections. vp1 is one of the major immunogenic capsid protein of ev71 and plays a crucial role in viral infection. antibodies against vp1 are important for virus neutral ...201121747954
dids blocks a chloride-dependent current that is mediated by the 2b protein of enterovirus 71. 201121747413
partial protection against enterovirus 71 (ev71) infection in a mouse model immunized with recombinant newcastle disease virus capsids displaying the ev71 vp1 fragment.enterovirus 71 (ev71) infection may cause severe neurological complications, particularly in young children. despite the risks, there are still no commercially available ev71 vaccines. hence, a candidate vaccine construct, containing recombinant newcastle disease virus capsids that display an ev71 vp1 fragment (npt-vp1(1-100) ) protein, was evaluated in a mouse model of ev71 infection. previously, it was shown that this protein construct provoked a strong immune response in vaccinated adult rabb ...201121837796
neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications.enterovirus 71 (ev71) has emerged as a significant pathogen causing large outbreaks in china for the past 3 years. developing an ev71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to ev71 infection remains unclear. we examined the neutralizing antibody titers in hfmd patients and compared them to those of asymptomatic healthy children and young adults. we found that 80% of hfmd patients became positive for neutralizing antibodies ag ...201121679417
host factors in enterovirus 71 replication.enterovirus 71 (ev71) infections continue to remain an important public health problem around the world, especially in the asia-pacific region. there is a significant mortality rate following such infections, and there is neither any proven therapy nor a vaccine for ev71. this has spurred much fundamental research into the replication of the virus. in this review, we discuss recent work identifying host cell factors which regulate the synthesis of ev71 rna and proteins. three of these proteins, ...201121715481
cleavage of the adaptor protein trif by enterovirus 71 3c inhibits antiviral responses mediated by toll-like receptor 3.enterovirus 71 (ev71) causes hand-foot-and-mouth disease and neurological complications in young children. although the underlying mechanisms remain obscure, impaired or aberrant immunity is thought to play a role. in infected cells, ev71 suppresses type i interferon responses mediated by retinoid acid-inducible gene i (rig-i). this involves the ev71 3c protein, which disrupts the formation of a functional rig-i complex. in the present study, we report that ev71 inhibits the induction of innate ...201121697485
immunoprotection elicited by an enterovirus type 71 experimental inactivated vaccine in mice and rhesus monkeys.a number of commonly recognized public health issues are associated with ev71 infection, including the induction of severe cases of hand-foot-and-mouth disease (hfmd). because of such issues, research and development of ev71 vaccine candidates is of growing importance. in the present study, an experimental ev71 inactivated vaccine was prepared, and its corresponding immunogenicity was analyzed. the immune responses and immunoprotective effect induced by the vaccine in mice and rhesus monkeys are ...201121722686
evolution of re-emergent virus and its impact on enterovirus 71 epidemics.enterovirus 71 (ev71), a member of the enterovirus genus in the picornaviridae family, has become an emergent infectious disease worldwide, most notably in asia. as a neurotropic virus, ev71 infection occasionally causes neurological diseases with pulmonary edema, which is fatal for children. in this review, we examine the epidemiology of ev71, with three waves of increased ev71 activity since the 1970s and discuss the genotypic changes in phylogeny between the outbreaks or epidemics. genetic ch ...201121715436
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