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expression of enterovirus 71 capsid protein vp1 in escherichia coli and its clinical application.the vpl gene of enterovirus 71 (ev71) was synthesized, construct a recombinant plasmid pet15b/vp1 and expressed in e. coli bl21. the recombinant vp1 protein could specifically react with ev71-infected patient sera without the cross-reaction with serum antibodies of coxsackievirus a16 (ca16), a4, a5, b3 and b5 as well as echovirus 6. in acute and convalescent phases, igm and igg antibodies of 182 serum samples were detected by elisa with recombinant vp1 protein as a coated antigen. the results sh ...201324688514
monoclonal antibodies for diagnosis of enterovirus 71.enterovirus 71 (ev71), one of the major causative agents of hand, foot, and mouth disease (hfmd), is now recognized as an emerging neurotropic virus in asia and may cause severe neurologic complications and mortalities. laboratory diagnosis of ev71 infection must be efficient and accurate, which could be accomplished by various immunoassays. in this study we use a live ev71 isolate, tainan/4643/98, with genotype c2 as an immunogen to sensitize balb/c (h-2(d)) mice and then generate the ev71-spec ...201324328741
seroprevalence of human enterovirus 71 and coxsackievirus a16 in guangdong, china, in pre- and post-2010 hfmd epidemic period.human enterovirus 71 and coxsackie a16 have caused many outbreaks in the last decade in mainland china, resulting in thousands of fatal cases. seroepidemiology which provides important information to document population immunity is rare in china.201324324604
[the pathogenic spectrum of hand, foot and mouth disease and molecular characterizations of human enterovirus 71 in inner mongolia autonomous region in 2010].to study the pathogenic spectrum of hand, foot and mouth disease (hfmd) and the molecular characterizations of human enteroviruses 71 (hev71) isolated from the clinical specimens of hfmd patients in inner mongolia in 2010. a total of 921 clinical specimens including stools and throat swabs were collected from hfmd patients in outpatient service in inner mongolia and then viral isolation was performed, the positive viral isolates were identified by using the real-time pcr method (detecting ev, he ...201323905475
molecular epidemiology of human enterovirus 71 strains in the nanchang region of china in 2011.hand, foot, and mouth disease (hfmd) is caused by enteroviruses, most commonly enterovirus 71 (ev71) and coxsackievirus a16 (ca16). in general, ev71 infection is more likely to induce severe complications and mortality than other enterovirus infections. the present study focuses on the molecular epidemiology of human ev71 strains in the nanchang region of china in 2011. overall, 651 specimens (throat or rectal swabs) were collected, and one-step reverse transcriptase-polymerase chain reaction wa ...201323514913
characterisation of enterovirus 71 replication kinetics in human colorectal cell line, ht29.hand, foot and mouth disease (hfmd), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as enterovirus 71 (ev71) and coxsackievirus a16 (ca16). however some hfmd caused by ev71 may further develop into severe neurological complications such as encephalitis and meningitis. the route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular ...201323875129
hand, foot, and mouth disease caused by coxsackievirus a6, thailand, 2012.in thailand, hand, foot, and mouth disease (hfmd) is usually caused by enterovirus 71 or coxsackievirus a16. to determine the cause of a large outbreak of hfmd in thailand during june-august 2012, we examined patient specimens. coxsackievirus a6 was the causative agent. to improve prevention and control, causes of hfmd should be monitored.201323631943
novel substituted heteroaromatic piperazine and piperidine derivatives as inhibitors of human enterovirus 71 and coxsackievirus a16.a series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein vp1. the preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against ev71 and coxsackievirus a16 with low cytotoxicity.201323629759
a new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease.this study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (hfmd). in this study, 1104 clinically diagnosed hfmd patients were included. enterovirus 71 (ev71), coxsackievirus a16 (ca16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (pcr) or reverse transcriptase pcr (rt-pcr). to evaluate the immune activation in hfmd patients, 8 cytokines and igm ...201323535205
detection of human enterovirus 71 and coxsackievirus a16 in an outbreak of hand, foot, and mouth disease in henan province, china in 2009.during 2009, an outbreak of hand, foot, and mouth disease (hfmd) enrolled 490 people in henan province, causing the death of two children. in order to investigate the pathogens responsible for this outbreak and characterize their genetic characteristics, a total of 508 clinical specimens (stool, throat swab, and vesicle fluid) were collected from the center for disease control and prevention of henan province. virological investigations (virus isolation, conventional reverse transcription pcr, a ...201323080402
an open conformation determined by a structural switch for 2a protease from coxsackievirus a16.coxsackievirus a16 belongs to the family picornaviridae, and is a major agent of hand-foot-and-mouth disease that infects mostly children, and to date no vaccines or antiviral therapies are available. 2a protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4g. here we present the crystal structure of coxsackievirus a16 2a protease, which interestingly forms hexamers in crystal as well a ...201324026848
vp2 dominated cd4+ t cell responses against enterovirus 71 and cross-reactivity against coxsackievirus a16 and polioviruses in a healthy population.enterovirus 71 (ev71)-associated hand-foot-mouth disease has become a major threat to public health in the asia-pacific region. although t cell immunity is closely correlated with clinical outcomes of ev71 infection, little is known about t cell immunity baseline against ev71 and t cell immunogenecity of ev71 ags in the population, which has restricted our understanding of immunoprotection mechanisms. in this study, we investigated the cellular immune responses against the four structural ags of ...201323863902
analysis and solution of false-positives when testing cva16 sera using an antibody assay against the ev71 virus.hand, foot and mouth disease (hfmd) in humans is caused mainly by enterovirus 71(ev71) and coxsackievirus a16 (cva16). ev71 is associated with severe hfmd cases but not cva16. use of igm-capture enzyme-linked immunosorbent assay (elisa) is important for the early diagnosis of ev71 infection, but cross-reactivity of the anti-cva16 igm antibody with ev71 produces false-positive results. in this report, we designed a new ev71 igm-capture elisa method using the ev71 vp1 peptide instead of the ev71 v ...201323707400
the development and application of the two real-time rt-pcr assays to detect the pathogen of hfmd.large-scale hand, foot, and mouth disease (hfmd) outbreaks have frequently occurred in china since 2008, affecting more than one million children and causing several hundred children deaths every year. the pathogens of hfmd are mainly human enteroviruses (hevs). among them, human enterovirus 71 (hev71) and coxsackievirus a16 (cva16) are the most common pathogens of hfmd. however, other hevs could also cause hfmd. to rapidly detect hev71 and cva16, and ensure detection of all hevs causing hfmd, t ...201323637836
coxsackievirus a6 and hand, foot and mouth disease: three case reports of familial child-to-immunocompetent adult transmission and a literature review.hand, foot and mouth disease (hfmd) is a highly contagious viral infection characterized by typical maculopapular or vesicular eruptions on the hands and feet and in the oral cavity. it affects predominantly children and/or immunocompromised adults. it usually follows a benign and self-limiting course. however, hfmd cases with severe or lethal complications such as encephalitis, meningitis, pulmonary edema and myocarditis have also been reported, mostly in children, but also in adults. high infe ...201324019771
novel marker for recombination in the 3'-untranslated region of members of the species human enterovirus a.human enterovirus a (hev-a) is a species in the genus enterovirus. viruses belonging to this species are often responsible for hand, foot and mouth disease and associated acute neurological disease. studies of the 3' untranslated region (utr) of human enterovirus 71 (hev71) revealed a possible role in virus replication. we compared the 3'-utrs of all members of hev-a and confirmed the presence of a secondary structure comprising three stem-loop domains (slds). sld-z is situated closest to the st ...201323178966
development of a coxsackievirus a16 neutralization assay based on pseudoviruses for measurement of neutralizing antibody titer in human serum.serum neutralizing antibody titers are indicative of protective immunity against coxsackievirus a16 (cv-a16) and enterovirus 71 (ev71), the two main etiological agents of hand, foot and mouth disease (hfmd), and provide the basis for evaluating vaccine efficacy. the current cv-a16 neutralization assay based on inhibition of cytopathic effects requires manual microscopic examination, which is time-consuming and labor-intensive. in this study, a high-throughput neutralization assay was developed b ...201323178532
a strain-specific epitope of enterovirus 71 identified by cryo-electron microscopy of the complex with fab from neutralizing antibody.enterovirus 71 (ev71) is a picornavirus that causes outbreaks of hand, foot, and mouth disease (hfmd), primarily in the asia-pacific area. unlike coxsackievirus a16, which also causes hfmd, ev71 induces severe neuropathology leading to high fatalities, especially among children under the age of 6 years. currently, no established vaccines or treatments are available against ev71 infection. the monoclonal antibody ma28-7 neutralizes only specific strains of ev71 that have a conserved glycine at am ...201323946455
accuracy of diagnostic methods and surveillance sensitivity for human enterovirus, south korea, 1999-2011.the epidemiology of enteroviral infection in south korea during 1999-2011 chronicles nationwide outbreaks and changing detection and subtyping methods used over the 13-year period. of 14,657 patients whose samples were tested, 4,762 (32.5%) samples were positive for human enterovirus (human ev); as diagnostic methods improved, the rate of positive results increased. a seasonal trend of outbreaks was documented. genotypes enterovirus 71, echovirus 30, coxsackievirus b5, enterovirus 6, and coxsack ...201323876671
comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.enterovirus 71 (ev71) infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (hfmd). this study aims to further characterize the specific immunological features in ev71-mediated hfmd patients presenting with differing degrees of disease severity.201323840697
atypical hand-foot-mouth disease in children: a hospital-based prospective cohort study.in 2010, we observed children with atypical presentations of hand-foot-mouth disease (hfmd), such as rashes on earlobes and faces, or bullae on trunks and bilateral limbs. hyperpigmentation later developed as the bullous lesions crusted. thus, we intended to study the etiology of the illness and the phylogeny of the pathogens.201323800163
a novel enterovirus and parechovirus multiplex one-step real-time pcr-validation and clinical experience.as the number of new enteroviruses and human parechoviruses seems ever growing, the necessity for updated diagnostics is relevant. we have updated an enterovirus assay and combined it with a previously published assay for human parechovirus resulting in a multiplex one-step rt-pcr assay. the multiplex assay was validated by analysing the sensitivity and specificity of the assay compared to the respective monoplex assays, and a good concordance was found. furthermore, the enterovirus assay was ab ...201323845901
characterization of enterovirus 71 and coxsackievirus a16 isolated in hand, foot, and mouth disease patients in guangdong, 2010.hand, foot, and mouth disease (hfmd) is an acute viral disease caused by human enteroviruses, especially human enterovirus 71 (hev71) and coxsackievirus a16 (cva16), and mainly affects infants and young children. after the outbreak in 2008 in fuyang, china, hfmd was classified as a category c notifiable infectious disease by the ministry of health of china.201323791223
emerging viral infections.this review highlights research and development in the field of emerging viral causes of encephalitis over the past year.201323591683
the antiviral effect of 7-hydroxyisoflavone against enterovirus 71 in vitro.enterovirus 71 (ev71) is the major causative agent of hand foot and mouth disease. and ev71 causes epidemics worldwide, particularly in the asia-pacific region. unfortunately, currently there is no approved vaccine or antiviral drug for ev71-induced disease prevention and therapy. in screening for anti-ev71 candidates, we found that 7-hydroxyisoflavone was active against ev71. 7-hydroxyisoflavone exhibited strong antiviral activity against three different ev71 strains. the 50% inhibitory concent ...201323464760
structural and functional analysis of coxsackievirus a9 integrin αvβ6 binding and uncoating.coxsackievirus a9 (cva9) is an important pathogen of the picornaviridae family. it utilizes cellular receptors from the integrin αv family for binding to its host cells prior to entry and genome release. among the integrins tested, it has the highest affinity for αvβ6, which recognizes the arginine-glycine-aspartic acid (rgd) loop present on the c terminus of viral capsid protein, vp1. as the atomic model of cva9 lacks the rgd loop, we used surface plasmon resonance, electron cryo-microscopy, an ...201323365426
hand, foot, and mouth disease: current scenario and indian perspective.hand, foot, and mouth disease (hfmd), first reported in new zealand in 1957 is caused by coxsackievirus a16 (cva16) and human enterovirus 71 (hev71) and occasionally by coxsackievirus a4-a7, a9, a10, b1-b3, and b5. this is characterized by erythematous papulo vesicular eruptions over hand, feet, perioral area, knees, buttocks and also intraorally mostly in the children. hfmd has been known for its self limiting course. only small scale outbreaks have been reported from united states, europe, aus ...201323442455
phylogenetic analysis of enterovirus 71 circulating in beijing, china from 2007 to 2009.the major pathogens of hand, foot and mouth disease (hfmd) in beijing, china from 2007 to 2009 were identified in this study. a total of 186 hfmd cases were included, and 136 cases (73%) were positive for enterovirus (ev). in 2007, 75% (27/36) were coxsackievirus a16 (ca16) positive and 19% (7/36) were enterovirus 71 (ev71) positive cases. however, ev71 was the predominant virus in 2008, when 56% (31/55) of the cases were positive for ev71 and 22% (12/55) were positive for ca16. in 2009, ev71 an ...201323418551
epidemiology and etiological characteristics of hand, foot and mouth disease in huizhou city between 2008 and 2011.to study epidemiological features and etiological characteristics of hand, foot and mouth disease (hfmd), 42,012 cases were investigated from april 2008 to december 2011 in huizhou, china. the average incidence rate was 21.16 per 10,000. the highest peak of hfmd incidence was detected between april and july each year, accounting for 55.93 % of all reported cases; another peak occurred in october through december, accounting for 24.17 % of the cases. of the reported cases, 89.75 % were in childre ...201323229012
glycyrrhizic acid as the antiviral component of glycyrrhiza uralensis fisch. against coxsackievirus a16 and enterovirus 71 of hand foot and mouth disease.the radices of glycyrrhiza uralensis fisch. and herbal preparations containing glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in china. glycyrrhizic acid (ga) is considered the principal component in glycyrrhiza spp. with a wide spectrum of antiviral activity.201323454684
3c protease of enterovirus 68: structure-based design of michael acceptor inhibitors and their broad-spectrum antiviral effects against picornaviruses.we have determined the cleavage specificity and the crystal structure of the 3c protease of enterovirus 68 (ev68 3c(pro)). the protease exhibits a typical chymotrypsin fold with a cys...his...glu catalytic triad; its three-dimensional structure is closely related to that of the 3c(pro) of rhinovirus 2, as well as to that of poliovirus. the phylogenetic position of the ev68 3c(pro) between the corresponding enzymes of rhinoviruses on the one hand and classical enteroviruses on the other prompted ...201323388726
hepatic damage caused by coxsackievirus b3 is dependent on age-related tissue tropisms associated with the coxsackievirus-adenovirus receptor.coxsackievirus b (cvb) and enterovirus 71 (ev71) are important causes of severe enteroviral diseases in neonates or young children in taiwan. cvb can cause fulminant hepatitis, myocarditis or meningoencephalitis. this study was designed to explore the role of coxsackievirus-adenovirus receptor (car) in the pathogenesis of cvb3-infected hepatocytes via in vitro and mice studies. cvb3 (cvb3/2630) was isolated from liver tissue of a neonate with fulminant hepatitis. cell lines a549, hela, hep2 and ...201323620416
atypical hand-foot-and-mouth disease associated with coxsackievirus a6 infection.hand-foot-and-mouth disease (hfmd) is an acute viral illness commonly caused by coxsackievirus (cv)-a16 and enterovirus 71 infections. recently, atypical hfmd has been reported in association with cv-a6, an uncommon enterovirus strain.201324035209
conformational plasticity of the 2a proteinase from enterovirus 71.the 2a proteinase (2a(pro)) is an enterovirally encoded cysteine protease that plays essential roles in both the processing of viral precursor polyprotein and the hijacking of host cell translation and other processes in the virus life cycle. crystallographic studies of 2a(pro) from enterovirus 71 (ev71) and its interaction with the substrate are reported here. ev71 2a(pro) was comprised of an n-terminal domain of a four-stranded antiparallel β sheet and a c-terminal domain of a six-stranded ant ...201323616646
human astrocytic cells support persistent coxsackievirus b3 infection.enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. here, we investigated the susceptibility of three human brain cell lines, ccf-sttg1, t98g, and sk-n-sh, to infection with three enterovirus serotypes: coxsackievirus b3 (cvb3), enterovirus 71, and coxsackievirus a9. persistent inf ...201324027313
genetic characterization of ev71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype d and recent emergence of a distinct lineage of subgenotype c2 in hong kong.enterovirus 71 (ev71) is a common etiological agent of hand, foot and mouth disease (hfmd) in children. ev71 epidemics have been reported in hong kong in recent years, and yet the genetic information of ev71 strains circulating in our locality is limited. the objective of this study was to investigate the genetic evolution of these ev71 isolates in hong kong over a 7-year period.201323822185
quinacrine impairs enterovirus 71 rna replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.since the 1980s, epidemics of enterovirus 71 (ev71) and other enteroviruses have occurred in asian countries and regions, causing a wide range of human diseases. no effective therapy is available for the treatment of these infections. internal ribosome entry sites (iress) are indispensable for the initiation of translation in enteroviruses. several cellular factors, as well as the ribosome, are recruited to the conserved ires during this process. quinacrine intercalates into the rna architecture ...201323301007
[observation on virus shedding periods of enterovirus-71 and coxsackievirus a 16 monitored by nucleic acids determination in stool samples of children with hand, foot and mouth disease].to observe the duration of enterovirus-71 (ev71) and coxsackievirus a 16 (coxa16) viral shedding in stool samples of children with hand, foot and mouth disease (hfmd) infected with ev71 and coxa16 and to explore the relationship between the duration of intestinal virus shedding and the severity of illness of children with hfmd.201324406235
enterovirus genotypes causing hand foot and mouth disease in shanghai, china: a molecular epidemiological analysis.a rapid expansion of hand, foot, and mouth disease (hfmd) outbreaks has occurred and caused deaths in china in recent years, but little is known about the other etiologic agents except enterovirus 71 (ev71) and coxsackievirus a 16 (ca16). the objective of this study is to determine the genotype compositions of enterovirus causing hfmd in shanghai and identify any associations between enterovirus types and clinical manifestations.201324148902
establishment of cell lines with increased susceptibility to ev71/ca16 by stable overexpression of scarb2.human enterovirus type 71 (ev71) and coxsackievirus a group type 16 (ca16) belong to human enterovirus species a of the family picornaviridae. these viruses are recognized as the major pathogens responsible for epidemics of hand-foot-mouth disease (hfmd), which presents with fever and vesicular eruptions of palms, soles of the feet or mouth. human scavenger receptor class b, member 2 (scarb2) has been identified as the receptor for both ev71 and ca16, as overexpression of scarb2 in cells can enh ...201323919614
seroepidemiology of human enterovirus71 and coxsackievirusa16 among children in guangdong province, china.hand, foot and mouth disease (hfmd) is a common pediatric illness. mainly induced by the enterovirus 71 and coxsackievirus a 16 infections, the frequently occurred hfmd outbreaks have become a serious public health problem in southeast asia. currently,only a few studies have investigated the human immunity to hfmd in china. in this study, we conducted a cohort study in guangdong province, china.201323855481
risk factors for neurologic complications of hand, foot and mouth disease in the republic of korea, 2009.in 2009, the first outbreak of hand, foot and mouth disease (hfmd) or herpangina (hp) caused by enterovirus 71 occurred in the republic of korea. this study inquired into risk factors associated with complications of hfmd or hp. a retrospective medical records review was conducted on hfmd or hp patients for whom etiologic viruses had been verified in 2009. one hundred sixty-eight patients were examined for this investigation. eighty patients were without complications while 88 were accompanied b ...201323341722
characterization of a novel monoclonal antibody reactive against the n-terminal region of enterovirus 71 vp1 capsid protein.hand, foot and mouth disease (hfmd) is a viral infectious disease caused by human enterovirus a, particularly enterovirus 71 (ev71) and coxsackievirus 16 (ca16) serotypes, with ev71 infection associated with severe neurological complications and mortality. lots of attention has been placed on elucidating viral epitopes, which is useful for ev71 viral research. in this study, a murine monoclonal antibody (mab 4) specific for ev71 was generated and mapped to target the n-terminal region of vp1 cap ...201323219932
seroepidemiology of human enterovirus71 and coxsackievirusa16 in jiangsu province, china.the major etiology of hand, foot and mouth disease (hfmd) is infection with human enterovirus a (hev-a). among subtypes of hev-a, coxsackievirusa16 (coxa16) and enterovirus 71 (ev71) are major causes for recurrent hfmd among infants and children in jiangsu province, mainland china. here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human ev71 and coxa16 infections in infants and children aged 0 to 15 years. the results may ...201223102275
challenges to licensure of enterovirus 71 vaccines.human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (ev71), which frequently involve neurological complications. ev71 vaccines are being evaluated in humans. however, several challenges to licensure of ev71 vaccines need to be addressed. firstly, ev71 and coxsackievirus a (ca) are frequently found to co-circulate and cause hand-foot-mouth disease (hfmd). a polyvalent vaccine that can provide protection against ev71 and prevalent ca are desirable. seco ...201222953003
encephalomyocarditis virus viroporin 2b activates nlrp3 inflammasome.nod-like receptors (nlrs) comprise a large family of intracellular pattern- recognition receptors. members of the nlr family assemble into large multiprotein complexes, termed the inflammasomes. the nlr family, pyrin domain-containing 3 (nlrp3) is triggered by a diverse set of molecules and signals, and forms the nlrp3 inflammasome. recent studies have indicated that both dna and rna viruses stimulate the nlrp3 inflammasome, leading to the secretion of interleukin 1 beta (il-1β) and il-18 follow ...201222916014
simultaneous determination of human enterovirus 71 and coxsackievirus b3 by dual-color quantum dots and homogeneous immunoassay.human enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have high risks for morbidity and mortality. a virus quantitation immunoassay has been proposed by employing two colored quantum dots (qds), antibodies of the virus, and graphene oxide (go). the qds are streptavidin-conjugated quantum dots (sa-qds), and the antibodies are biotinylated antibodies. biotinylated ev71 antibody (ab1) was associated with 525 nm green colored sa-qds via biotin-streptavidin interaction forming qds-ab1, whereas bio ...201222390751
copi is required for enterovirus 71 replication.enterovirus 71 (ev71), a member of the picornaviridae family, is found in asian countries where it causes a wide range of human diseases. no effective therapy is available for the treatment of these infections. picornaviruses undergo rna replication in association with membranes of infected cells. copi and copii have been shown to be involved in the formation of picornavirus-induced vesicles. replication of several picornaviruses, including poliovirus and echovirus 11 (ev11), is dependent on cop ...201222662263
antigenic diversity of enteroviruses associated with nonpolio acute flaccid paralysis, india, 2007-2009.because of the broadened acute flacid paralysis (afp) definition and enhanced surveillance, many nonpolio afp (np-afp) cases have been reported in india since 2005. to determine the spectrum of nonpolio enterovirus (npev) serotypes associated with np-afp from polio-endemic and -free regions, we studied antigenic diversity of afp-associated npevs. of fecal specimens from 2,786 children with np-afp in 1 polio-endemic and 2 polio-free states, 823 (29.5%) were positive for npevs in rd cells, of whic ...201223092622
[outbreak of acute enterovirus intestinal infection in sakhalin region in august 2010].the investigation of cases of acute intestinal infections in the sakhalin region of russia in august, 2010 is described. epidemiological and molecular biological studies were conducted. after initial pcr screening and determining the nucleotide sequences of the positive samples the following enteroviruses were found: coxsackie a2 - 42 samples (45%), coxsackie a4--31 sample (34%), enterovirus 71--6 samples (6,5%), coxsackievirus b5--6 samples (6,5%), coxsackie b3--4 samples (4%) and coxsackie b1- ...201222642180
human scarb2-dependent infection by coxsackievirus a7, a14, and a16 and enterovirus 71.human enterovirus species a (hev-a) consists of at least 16 members of different serotypes that are known to be the causative agents of hand, foot, and mouth disease (hfmd), herpangina, and other diseases, such as respiratory disease and polio-like flaccid paralysis. enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the major causative agents of hfmd. cva5, cva6, cva10, and cva12 mainly cause herpangina or are occasionally involved with sporadic cases of hfmd. we have previously shown tha ...201222438546
detection of human enterovirus 71 and coxsackievirus a16 in children with hand, foot and mouth disease in china.the aims of the present study were to investigate the genetic characteristics of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) strains in china and to evaluate the relationship between the genotypes of cva16 and ev71 and their geographical distribution. a total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (hfmd) in zhejiang province. the presence of enteroviruses was determined ...201222218731
enterovirus 71 blocks selectively type i interferon production through the 3c viral protein in mice.type i interferons (ifns) represent an essential innate defense mechanism for controlling enterovirus 71 (ev 71) infection. mice inoculated with ev 71 produced a significantly lower amount of type i ifns than those inoculated with poly (i:c), adenovirus type v, or coxsackievirus b3 (cb3). ev 71 infection, however, mounted a proinflammatory response with a significant increase in the levels of serum and brain interleukin (il)-6, monocyte chemoattractant protein-1, tumor necrosis factor, and ifn-γ ...201222997081
immunological and biochemical characterization of coxsackie virus a16 viral particles.coxsackie virus a16 (cva16) infections have become a serious public health problem in the asia-pacific region. it manifests most often in childhood exanthema, commonly known as hand-foot-and-mouth disease (hfmd). there are currently no vaccine or effective medical treatments available.201223226233
rapid and sensitive identification of rna from the emerging pathogen, coxsackievirus a6.hand, foot and mouth disease (hfmd) is caused by members of the family picornaviridae in the genus enterovirus. it has been reported that coxsackievirus a6 (cva6) infections are emerging as a new and major cause of epidemic hfmd. sporadic hfmd cases positive for cva6 were detected in the mainland of china in recent years. to strengthen the surveillance of cva6 infections and outbreak control, the clinical diagnosis is urgently needed to distinguish the cva6 infection disease from other infection ...201223194501
a novel minicircle vector based system for inhibting the replication and gene expression of enterovirus 71 and coxsackievirus a16.enterovirus 71 (ev 71) and coxsackievirus a16 (ca 16) are two major causative agents of hand, foot and mouth disease (hfmd). they have been associated with severe neurological and cardiological complications worldwide, and have caused significant mortalities during large-scale outbreaks in china. currently, there are no effective treatments against ev 71 and ca 16 infections. we now describe the development of a novel minicircle vector based rna interference (rnai) system as a therapeutic approa ...201222921338
replication kinetics of coxsackievirus a16 in human rhabdomyosarcoma cells.coxsackievirus a16 (cva16), together with enterovirus type 71 (ev71), is responsible for most cases of hand, foot and mouth disease (hfmd) worldwide. recent findings suggest that the recombination between cva16 and ev71, and the co-circulation of these two viruses may have contributed to the increase of hfmd cases in china over the past few years. it is therefore important to further understand the virology, epidemiology, virus-host interactions and host pathogenesis of cva16. in this study, we ...201222899429
[etiology of hand-foot-and-mouth disease seen in nanjing in 2010 and molecular characteristics analysis of ev71].to study the etiological agent of hand-foot-and-mouth disease (hfmd), and to genetically characterize enterovirus 71 (ev71) isolated from clinical specimens of hfmd patients in nanjing in 2010.201222801226
[epidemiology and etiology of hand-foot-and-mouth disease seen in jiangsu province from 2008 to 2010].to analyze the etiological and epidemiological characteristics of hand-foot-and-mouth disease (hfmd) seen in jiangsu province from 2008 to 2010, and provide evidence for its prevention and control.201222801225
antiviral ability of kalanchoe gracilis leaf extract against enterovirus 71 and coxsackievirus a16.pandemic infection or reemergence of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. however, effective therapeutic drugs against ev71 and cva16 are rare. kalanchoe gracilis (l.) dc is used for the treatment of injuries, pain, and inflammation. this study investigated antiviral effects of k. gracilis leaf extr ...201222666293
antigenic characteristics of the complete and truncated capsid protein vp1 of enterovirus 71.the complete vp1 protein of enterovirus 71 (ev71) and a series of truncations were expressed in escherichia coli and their antigenic characteristics were studied. immunoblot analysis showed the major immunoreactive region of the vp1 protein was located in the n-terminal portion at position of amino acid (aa) 1-100. the complete vp1 possessed strong cross-reactivity with antisera against coxsackievirus a16 (ca16) and echovirus 6 (echo6), while the truncated fragment at position 1-100 aa only had ...201222659489
simultaneous detection of enterovirus 71 and coxsackievirus a16 using dual-colour upconversion luminescent nanoparticles as labels.we highlight a novel fluorescence analysis for sensitive and selective detection of ev-71 and cv-a16 by combining labelling technology based on dual-colour upconversion fluorescence nanoparticles (ucnps) with magnetic bioseparation and concentration technology based on magnetite nanoparticles (mnps).201222498910
cellular receptors for human enterovirus species a.human enterovirus species a (hev-a) is one of the four species of hev in the genus enterovirus in the family picornaviridae. among hev-a, coxsackievirus a16 (cva16) and enterovirus 71 (ev71) are the major causative agents of hand, foot, and mouth disease (hfmd). some other types of hev-a are commonly associated with herpangina. although hfmd and herpangina due to hev-a are common febrile diseases among infants and children, ev71 can cause various neurological diseases, such as aseptic meningitis ...201222470371
etiologic and epidemiologic analysis of hand, foot, and mouth disease in guangzhou city: a review of 4,753 cases.this study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (hfmd) cases that occurred between 2008 and 2010 in guangzhou city, to help develop and implement precautionary measures applicable for future outbreaks.201222964289
identification and characterization of a monoclonal antibody recognizing the linear epitope rvadvi on vp1 protein of enterovirus 71.several large outbreaks of hand-foot-mouth disease (hfmd) have occurred in the asian-pacific region since 1997, with enterovirus 71 (ev71) and/or coxsackievirus a16 (cav16) as the main causative agents. despite the close genetic relationship between the two viruses, only ev71 is associated with severe clinical manifestations and deaths. effective antiviral treatment and vaccines are not available. high-quality monoclonal antibodies (mabs) are necessary to improve the accuracy of the diagnosis of ...201222930511
evidences for intertypic and intratypic recombinant events in ev71 of hand, foot and mouth disease during an epidemic in hubei province, china, 2011.humane enterovirus 71 (hev 71) is a common contagious agent of hand, foot and mouth disease (hfmd) which is normally mild but can caused deaths and severe neurological complications. in april 2011, an unpredicted hfmd outbreak in xiangyang city of hubei province in china resulted in a high aggregation of hfmd cases including fatal cases and many severe cases. in this study, 71 clinical specimens were collected according to the different symptoms and rna extraction and rt-pcr amplification were p ...201222922556
comparative genetic analysis of vp4, vp1 and 3d gene regions of enterovirus 71 and coxsackievirus a16 circulating in malaysia between 1997-2008.three genomic regions, vp4 capsid, vp1 capsid and 3d rna polymerase of human enterovirus 71 (ev-71) and coxsackievirus a16 (cv-a16) were sequenced to understand the evolution of these viruses in malaysia. a total of 42 ev-71 and 36 cv-a16 isolates from 1997- 2008 were sequenced. despite the presence of many ev-71 subgenotypes worldwide, only subgenotypes b3, b4, b5, c1 and c2 were present in malaysia. importation of other subgenotypes such as c3, c4/d and c5 from other countries was infrequent. ...201223018509
enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor.enterovirus 71 (ev-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. to date, four ev-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish ev-71 infection, implying that there is an as yet undiscovered receptor(s). since ev-71 has a wide range of tissue tropisms, we hypothesize that ev-71 infections ma ...201223097443
[genetic characteristics of enterovirus 71 vp1 and epidemiology of hand-foot-mouth disease in xinxiang in 2011].the study was performed to examine the enterovirus 71(ev71) vp1 genetic feature and the epidemiology of hand-foot-mouth disease (hfmd) in xinxiang in 2011. real-time rt-pcr was used for the detection of pan-enterovirus, coxsackievirus a 16(ca16) and ev71 from stool specimens of hfmd. the vp1 region was amplified from 10 ev71 positive samples and the products were sequenced. ev71 genotypes were characterized by homology and phylogenetic tree analyses. additionally, epidemic data of xinxiang hfmd ...201223367569
[comparison of different molecular assays for the rapid detection of enterovirus 71 (ev71)].molecular detection of enterovirus (ev)71 rna based on pcr methods is a quick and sensitive approach. at present, different pcr-based methods for ev71 rna detection are available, but comparisons of results obtained using different approaches are limited. this study is to compare the analytical sensitivity and specificity of different real-time reverse transcription-polymerase chain reaction (rrt-pcr) and conventional reverse transcription-polymerase chain reaction (crt-pcr) assays for enterovir ...201223367568
enterovirus 71-induced neurological disorders in young gerbils, meriones unguiculatus: development and application of a neurological disease model.a reliable disease model mimicking enterovirus 71 (ev71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to ev71 infection after they reach the age of 6 days. in this study, 21-day-old gerbils inoculated intraperitoneally (ip) with a non mouse-adapted ev71 strain developed neurological lesion-related s ...201223284845
evaluation of a direct reverse transcription loop-mediated isothermal amplification method without rna extraction for the detection of human enterovirus 71 subgenotype c4 in nasopharyngeal swab specimens.human enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd) worldwide and has been associated with neurological complications which resulted in fatalities during recent outbreak in asia pacific region. a direct reverse transcription loop-mediated isothermal amplification (direct rt-lamp) assay using heat-treated samples without rna extraction was developed and evaluated for the detection of ev71 subgenotype c4 in nasopharyngeal swab specimens. the analytical ...201223272248
[analysis on epidemiology and the main clinical symptoms of viral encephalitis in gansu, 2009-2011].to understand the epidemiological characteristics and the main clinical symptoms of viral encephalitis in gansu.201223363967
[typing and identification of non-polio enterovirus from acute flaccid paralysis cases in ningxia, 1997-2011].to identify the serotype of 73 non-polio enterovirus (npev) strains from acute flaccid paralysis (afp) cases in ningxia province, during 1997 - 2011.201223290905
[etiological detection of severe hand-food-mouth disease and related genetic characteristics of enterovirus type 71 infection in beijing, 2010].to study the etiological detection on samples from severe hand-foot-mouth disease (hfmd) cases and the genetic characteristics of enterovirus type 71 (ev71) isolates from severe patients in beijing, 2010.201223290804
coxsackievirus mutants that can bypass host factor pi4kiiiβ and the need for high levels of pi4p lipids for replication.rna viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are unlikely to mutate in response to therapy. we recently demonstrated that phosphatidylinositol-4-kinase iiiβ (pi4kiiiβ) and its product phosphatidylinositol-4-phosphate (pi4p) are essential for replica ...201222945356
[association of hla-g 14bp gene polymorphisms and plasma shla-g level with susceptibility to ev71 infection in children].explore the relationship between the hla-g 14bp insertion/deletion polymorphism and the infection of enterovirus 71 (ev71) for children.201223627021
[transmission and prevalence patterns of c4a evolutionary lineage of human enterovirus 71 circulating in mainland of china, 2008-2010].to understand the evolutionary relationship between the c4a evolutionary lineage of human enterovirus 71 (hev71) strains circulating in mainland of china during 2008-2010 and 2008 fuyang strains and study the prevalence and transmission patterns of 2008 fuyang strains.201223627020
pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia and now is being recognized as an important neurotropic virus. effective medications and prophylactic vaccine against ev71 infection are urgently needed. based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated ev71 vaccine candidate has been developed and currently in human phase 1 clinical trial.201222529942
production of ev71 vaccine candidates.enterovirus 71 (ev71) is now recognized as an emerging neurotropic virus in asia and with coxsackie virus (cv) it is the other major causative agent of hand-foot-mouth diseases (hfmd). effective medications and/or prophylactic vaccines against hfmd are urgently needed. from a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of d ...201222992566
immunological evaluation and comparison of different ev71 vaccine candidates.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are major causative agents of hand, foot, and mouth diseases (hfmds), and ev71 is now recognized as an emerging neurotropic virus in asia. effective medications and/or prophylactic vaccines against hfmd are not available. the current results from mouse immunogenicity studies using in-house standardized rd cell virus neutralization assays indicate that (1) vp1 peptide (residues 211-225) formulated with freund's adjuvant (cfa/ifa) elicited low v ...201223008736
occurrence of hand-foot-and-mouth disease pathogens in domestic sewage and secondary effluent in xi'an, china.hand, foot and mouth disease (hfmd), caused by a group of enteric viruses such as enterovirus 71 (ev71), coxsackievirus a16 (cva16) and coxsackievirus a10 (cva10), is heavily epidemic in east asia. this research focused on investigating the occurrence of hfmd pathogens in domestic sewage and secondary effluent before disinfection in a wastewater treatment plant (wwtp) in xi'an, the largest megacity in northwest china. in order to simultaneously detect all three hfmd pathogens, a semi-nested rt-p ...201222446307
outbreak of hand, foot and mouth disease/herpangina associated with coxsackievirus a6 and a10 infections in 2010, france: a large citywide, prospective observational study.hand, foot and mouth disease (hfmd) and herpangina (ha) are frequently caused by several distinct serotypes belonging to the human enterovirus a species (heva). enterovirus 71 is considered as a significant public health threat because of rare but fatal neurological complications. a sentinel surveillance system involving paediatricians from clermont-ferrand (france) was set up to determine the clinical and epidemiological characteristics of hfmd/ha associated with enterovirus infections. a stand ...201222404077
evaluation of human enterovirus 71 and coxsackievirus a16 specific immunoglobulin m antibodies for diagnosis of hand-foot-and-mouth disease.abstract: background: hand-foot-and-mouth disease (hfmd) is caused mainly by the human enterovirus type 71 (hev71) and the coxsackievirus a group type 16 (cva16). large outbreaks of disease have occurred frequently in the asia-pacific region. reliable methods are needed for diagnosis of hfmd in childen. igm-capture elisa, with its notable advantages of convenience and low cost, provides a potentially frontline assay. we aimed to evaluate the newly developed igm-capture elisas for hev71 and cva1 ...201222234169
enterovirus 71 disrupts interferon signaling by reducing the interferon receptor i.the recent outbreak of enterovirus 71 (ev71) infected millions of children and caused over 1,000 deaths. to date, neither effective vaccine nor antiviral treatment is available for ev71 infection. interferons (ifns) have been successfully applied for treating patients such as hepatitis b and c viral infections for decades but failed to treat ev71 infections. here, we provide the evidence that ev71 antagonizes type i ifn signaling by reducing the level of interferon receptor 1 (ifnar1). we show t ...201222258259
detection of human enterovirus 71 reverse transcription loop-mediated isothermal amplification (rt-lamp).aims:  in this study, a one-step, single-tube reverse transcription loop-mediated isothermal amplification (rt-lamp) assay was developed and validated for the detection of human enterovirus 71 (ev71), the major aetiological agent of hand, foot and mouth disease (hfmd). methods and results:  reverse transcription loop-mediated isothermal amplification assay was optimized to amplify vp1 gene in the presence of a specific primer set and bst dna polymerase at an isothermal temperature of 63°c for 1  ...201222256968
MEK1-ERKs signal cascade is required for the replication of Enterovirus 71 (EV71).The role of the MEK1-ERK signaling cascade in the replication cycle of Enterovirus 71 (EV71), the primary cause of hand, foot and mouth disease (HFMD), has been analyzed. In vitro infection with EV71 induced a biphasic activation of ERK. The two phases of activation appeared to be triggered by different mechanisms, with the first phase being activated by the binding of viral particles to the membrane receptor of host cells and the second probably being in response to the production of new virus ...201222101247
[cloning, expression and antigenic analysis of vp1-vp4 gene encoding the structural protein of coxsackie virus a16].to clone and express vp1-vp4 genes encoding the structural proteins of coxsackie virus a16 and analyze the antigenicity of the expressed recombinant proteins.201223268395
development and characterization of a stable egfp enterovirus 71 for antiviral screening.enterovirus 71 (ev71) is one of the major causative agents for hand, foot, and mouth disease. there is currently no clinically approved vaccine or antiviral treatment for ev71 infection. to facilitate antiviral drug discovery, we developed an infectious cdna clone of an epidemic strain of ev71 and a stable egfp reporter ev71. the reporter virus was generated by engineering the egfp gene between the 5' untranslated region and vp4 gene of the ev71 genome. vero cells transfected with the cdna clone ...201223267829
Modification of the untranslated regions of human enterovirus 71 impairs growth in a cell-specific manner.Human enterovirus 71 (HEV71) is the causative agent of hand, foot, and mouth disease and associated acute neurological disease. At present, little is known about the genetic determinants of HEV71 neurovirulence. Studies of related enteroviruses have indicated that the untranslated regions (UTRs), which control virus-directed translation and replication, also exert significant influence on neurovirulence. We used an infectious cDNA clone of a subgenogroup B3 strain to construct and characterize c ...201222031931
[detection the pathogens and analysis the clinical characteristics in children with hand, foot and mouth disease in shanghai during 2009-2011].to investigate the epidemic characteristics of etiological agents and analyze the clinic differences in children with hand, foot and mouth diseases in shanghai.201223547454
[isolation and sequence analysis on virus of hfmd with encephalitis in yantal city].to learn about the pathogen spectrum and genetic characterization of hfmd with encephalitis in yantai city.201223547453
enterovirus 71 causes hand, foot and mouth disease outbreak in cambodia. 201223448647
[etiology surveillance of hand-foot-mouth disease in henan province between 2008 and 2011].to understand etiological types and distribution features of hand-foot-mouth disease (hfmd) in henan province between 2008 and 2011.201223363860
in vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection.enterovirus 71(ev71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. more effective antiviral drugs are needed to prevent or reduce ev71-related disease and complications. however, there are no standard models currently in use to evaluate activity against ev71 infection both in vitro and in vivo. in this study, the activity of ribavirin and pleconaril against ev71 infection was evaluated in two models. an in vitro e ...201222245989
far upstream element binding protein 1: a commander of transcription, translation and beyond.the far upstream binding protein 1 (fbp1) was first identified as a dna-binding protein that regulates c-myc gene transcription through binding to the far upstream element (fuse) in the promoter region 1.5 kb upstream of the transcription start site. fbp1 collaborates with tfiih and additional transcription factors for optimal transcription of the c-myc gene. in recent years, mounting evidence suggests that fbp1 acts as an rna-binding protein and regulates mrna translation or stability of genes, ...201222926519
molecular characterization of human enteroviruses in the central african republic: uncovering wide diversity and identification of a new human enterovirus a71 genogroup.human enteroviruses (hev) are among the most common viruses infecting humans. their circulation has been widely studied in most parts of the world but not in sub-saharan africa, where poliomyelitis remains prevalent. we report here the molecular characterization of 98 nonpoliovirus (non-pv) hev strains isolated from 93 randomly selected cell culture-positive supernatants from stool samples collected from 1997 through 2006 from children with acute flaccid paralysis living in the central african r ...201222337981
inhibition of enterovirus 71 (ev-71) infections by a novel antiviral peptide derived from ev-71 capsid protein vp1.enterovirus 71 (ev-71) is the main causative agent of hand, foot and mouth disease (hfmd). in recent years, ev-71 infections were reported to cause high fatalities and severe neurological complications in asia. currently, no effective antiviral or vaccine is available to treat or prevent ev-71 infection. in this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of ev-71. ninety five synthetic peptides (15-mers) overlapping the entire e ...201222563456
distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications.abstract: background: to explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (hfmd) complicated with nervous system disease. 234 hospitalized hfmd patients treated in shengjing hospital, liaoning province were analyzed retrospectively. based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. based on the detected p ...201222230340
characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection.enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease (hfmd) and is associated with severe neurologic complications and mortalities. at present, there is no vaccine or therapeutic available for treatment.201222279543
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