Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
[epidemiological and etiological characteristics of hand-foot-mouth disease in ningbo, zhejiang province, 2008-2011].to analyze the epidemiological characteristics of hand foot and mouth disease (hfmd) in ningbo.201323937841
enterovirus 71 binding to psgl-1 on leukocytes: vp1-145 acts as a molecular switch to control receptor interaction.some strains of enterovirus 71 (ev71), but not others, infect leukocytes by binding to a specific receptor molecule: the p-selectin glycoprotein ligand-1 (psgl-1). we find that a single amino acid residue within the capsid protein vp1 determines whether ev71 binds to psgl-1. examination of capsid sequences of representative ev71 strains revealed that the psgl-1-binding viruses had either a g or a q at residue 145 within the capsid protein vp1 (vp1-145g or q), whereas psgl-1-nonbinding viruses ha ...201323935488
patterns of polymorphism and divergence in the vp1 gene of enterovirus 71 circulating in the asia-pacific region between 1994 and 2013.enterovirus 71 has been implicated in several outbreaks of hand, foot and mouth disease in the asia-pacific region. the present study aimed to achieve comprehensive evolutionary dynamic aspects of ev71 during 1994-2013, based on phylogenetic analyses of the vp1 sequences. the results indicated that 4 genotypes, namely c4, c1, c2 and b4 are the predominant strains, especially in southeast asian countries. no common ancestor was shared in different countries. fourteen sites of substitutions were d ...201323933074
plasma b-type natriuretic peptide study in children with severe enterovirus 71 infection: a pilot study.severe enterovirus 71 (ev71) infections in children can result in acute heart failure. b-type natriuretic peptide (bnp) is a good biomarker of myocardial stress. the purpose of this study was to use plasma bnp for the detection of ev71 infection with cardiac involvement.201323932576
[retrospective analysis of clinical and epidemiological characteristics of hand-foot-and-mouth disease deceased cases in zhejiang province].to understand the clinical and epidemiological characteristics of hand-foot-and-mouth disease (hfmd) deceased cases.201323927799
genetic and antigenic characterization of enterovirus 71 in ho chi minh city, vietnam, 2011.enterovirus 71 (ev71) frequently causes fatal infections in young children in asia. in 2011, ev71 epidemics occurred in southern vietnam. we conducted genetic and antigenic analysis of the ev71 isolates and found that 94% of them were genotype c4a related to two lineages circulating in china and 6% were genotype c5 which have circulated in vietnam since 2003. antigenic variants were not detected. ev71 vaccines are being developed. longitudinal enterovirus surveillance data are critical to formul ...201323922846
identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections.rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. other members of the genus can cause life-threatening acute neurological infections. there is currently no antiviral drug approved for the treatment of such infections. we have identified a series of potent, broad-spectrum antiviral compounds that inhibit the replication of the human rhinovirus, coxsackie virus, poliovirus, and enterovirus-71. the me ...201324900715
[identification and characterization of enterovirus 71 isolated in yunnan province].identification and characterization of eight enterovirus 71 samples isolated from yunnan province.201324579470
characterization of enterovirus 71 capsids using subunit protein-specific polyclonal antibodies.enterovirus 71 (ev71), a member of the enterovirus genus of the picornaviridae family, is one of the major causative agents of hand-foot-and-mouth disease (hfmd), which is prevalent in the asia-pacific region. in this article, a set of capsid subunit protein-specific antibodies was used to characterize the ev71 structural protein processing and to determine the composition and assembly of ev71 capsids. sds-page and western blot analyses showed that the capsids of a purified ev71 preparation, whi ...201323046991
recombinant vp1 protein expressed in pichia pastoris induces protective immune responses against ev71 in mice.human enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease and is also associated with serious neurological diseases in children. currently, there are no effective antiviral drugs or vaccines against ev71 infection. vp1, one of the major immunogenic capsid proteins of ev71, is widely considered to be the candidate antigen for an ev71 vaccine. in this study, vp1 of ev71 was expressed as a secretory protein with an n-terminal histidine tag in the methylotrophi ...201323159634
microrna-548 down-regulates host antiviral response via direct targeting of ifn-λ1.interferon (ifn)-mediated pathways are a crucial part of the cellular response against viral infection. type iii ifns, which include ifn-λ1, 2 and 3, mediate antiviral responses similar to type i ifns via a distinct receptor complex. ifn-λ1 is more effective than the other two members. transcription of ifn-λ1 requires activation of irf3/7 and nuclear factor-kappa b (nf-κb), similar to the transcriptional mechanism of type i ifns. using reporter assays, we discovered that viral infection induced ...201323150165
fluorescent primer-based in vitro transcription system of viral rna-dependent rna polymerases.viral infection is a leading cause of disease and death. although vaccines are the most effective method of controlling viral infections, antiviral drugs are also important. here, we established an in vitro transcription system by using fluorescein isothiocyanate-conjugated primers for rna polymerases of viruses that are important disease-causing human pathogens (influenza, hepatitis c, japanese encephalitis viruses, and enterovirus 71). this technology will allow us to analyze rna polymerase ac ...201323103398
ribavirin-resistant mutants of human enterovirus 71 express a high replication fidelity phenotype during growth in cell culture.it has been shown in animal models that ribavirin-resistant poliovirus with a g64s mutation in its 3d polymerase has high replication fidelity coupled with attenuated virulence. here, we describe the effects of mutagenesis in the human enterovirus 71 (hev71) 3d polymerase on ribavirin resistance and replication fidelity. seven substitutions were introduced at amino acid position 3d-g64 of a hev71 full-length infectious cdna clone (26m). viable clone-derived virus populations were rescued from th ...201323175376
cleavage of interferon regulatory factor 7 by enterovirus 71 3c suppresses cellular responses.enterovirus 71 (ev71) is a positive-stranded rna virus which is capable of inhibiting innate immunity. among virus-encoded proteins, the 3c protein compromises the type i interferon (ifn-i) response mediated by retinoid acid-inducible gene-i (rig-i) or toll-like receptor 3 that activates interferon regulatory 3 (irf3) and irf7. in the present study, we report that enterovirus 71 downregulates irf7 through the 3c protein, which inhibits the function of irf7. when expressed in mammalian cells, the ...201323175366
antigenic analysis of divergent genotypes human enterovirus 71 viruses by a panel of neutralizing monoclonal antibodies: current genotyping of ev71 does not reflect their antigenicity.in recent year, enterovirus 71 (ev71)-associated hand, foot and mouth disease (hfmd) has become an important public health issue in china. ev71 has been classified into genotypes a, b1-b5 and c1-c5. with such genetic diversity, whether the convalescent or recovery antibody responses can cross-protect infections from other genotypes remains a question. understanding of the antigenicity of such diverse genetic ev71 isolates is crucial for the ev71 vaccine development. here, a total of 186 clones a ...201323088887
quantification of the dynamics of enterovirus 71 infection by experimental-mathematical investigation.enterovirus 71 (ev71) is the causative agent of hand-foot-and-mouth disease and can trigger neurological disorders. ev71 outbreaks are a major public health concern in asia-pacific countries. by performing experimental-mathematical investigation, we demonstrate here that viral productivity and transmissibility but not viral cytotoxicity are drastically different among ev71 strains and can be associated with their epidemiological backgrounds. this is the first report demonstrating the dynamics of ...201323097444
lncrna expression signatures in response to enterovirus 71 infection.outbreaks of hand, foot, and mouth disease caused by enterovirus 71 (ev71) have become considerable threats to the health of infants and young children. to identify the cellular long noncoding rnas (lncrnas) involved in the host response to ev71 infection, we performed comprehensive lncrna and mrna profiling in ev71-infected rhabdomyosarcoma cells through microarray. we observed the differential expression of more than 4800 lncrnas during infection. further analysis showed 160 regulated enhancer ...201323220233
impact of endothelial nitric oxide synthase gene polymorphism on severity of enterovirus 71-infection in chinese children.genetic polymorphism g894t on the endothelial nitric oxide synthase (enos) gene has been reported as a susceptibility factor in a number of diseases, but evidence of its effect on enterovirus 71 (ev71) infection is lacking. this study investigated the possible association between this polymorphism (rs1799983) and disease severity in chinese children with ev71 infection.201324140479
adoptive transfer of macrophages from adult mice reduces mortality in mice infected with human enterovirus 71.human enterovirus 71 (ev71) causes hand, foot and mouth disease in children under 6 years of age, and the neurological complications of this virus can lead to death. until now, no vaccines or drugs have been available for the clinical control of this epidemic. macrophages can engulf pathogens and mediate a series of host immune responses that play a role in the defence against infectious diseases. using immunohistochemistry, we observed the localizations of virus in muscle tissues of ev71-infect ...201323065110
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 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
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
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
emerging viral infections.this review highlights research and development in the field of emerging viral causes of encephalitis over the past year.201323591683
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
formalin-inactivated ev71 vaccine candidate induced cross-neutralizing antibody against subgenotypes b1, b4, b5 and c4a in adult volunteers.enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia. no effective ev71 vaccine is available. a randomized and open-label phase i clinical study registered with clinicaltrials.gov #nct01268787, aims to evaluate the safety, reactogenicity and immunogenicity of a formalin-inactivated ev71 vaccine candidate (ev71vac) at 5- and 10-µg doses. in this study we report the cross-neutralizing antibody responses from each volunteer against different subgenotype ...201324278177
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
epidemiology and clinical characteristics of hand foot, and mouth disease in a shenzhen sentinel hospital from 2009 to 2011.we investigated the epidemiological and clinical data of all hand, foot, and mouth disease (hfmd) cases in a sentinel hospital of shenzhen, china from 2009 to 2011.201324225231
[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
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
coxsackievirus a6-induced hand-foot-mouth disease.hand-foot-mouth disease (hfmd) is an acute, self-limited, highly contagious viral illness that commonly affects children younger than 5 years. it is most typically caused by enterovirus 71 or coxsackievirus a16 and results in asymptomatic infection or mild disease. immunocompetent adults are rarely affected. recently, there have been increasing reports of a more severe form of hfmd associated with fevers, joint pains, and widespread painful eruptions. some of these patients required hospitalizat ...201324172861
eupafolin and ethyl acetate fraction of kalanchoe gracilis stem extract show potent antiviral activities against enterovirus 71 and coxsackievirus a16.enterovirus 71 (ev71) and coxsackievirus a16 (coxa16) are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. kalanchoe gracilis, da-huan-hun, is a chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. our prior report (2012) cited k. gracilis leaf extract as moderately active against ev71 and coxa16. this study further rates antienteroviral potent ...201324078828
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
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
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
oral immunization of mice using bifidobacterium longum expressing vp1 protein from enterovirus 71.bifidobacterium longum is an attractive candidate for delivering biologically active proteins by the mucosal route due to its non-pathogenic and colonizing properties. enterovirus 71 (ev71) has aroused widespread attention recently due to several epidemics, and great attention should be paid to the fact that there are currently no effective antiviral drugs or vaccines against ev71 infection. in this report, we described a recombinant b. longum that could be used to develop an oral vaccine agains ...201323275129
adaptation of enterovirus 71 to adult interferon deficient mice.non-polio enteroviruses, including enterovirus 71 (ev71), have caused severe and fatal cases of hand, foot and mouth disease (hfmd) in the asia-pacific region. the development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. in this study, a mouse adapted ev71 strain was produced by conducting serial passages through a129 (α/β interferon (ifn) receptor deficient) and ag129 (α/β, γ ifn receptor deficient) mice. a b2 sub genotype of ...201323527208
human igg subclasses against enterovirus type 71: neutralization versus antibody dependent enhancement of infection.the emerging human enterovirus 71 (ev71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. human intravenous immunoglobulin (ivig) is clinical used in treating severe ev71 infections. however, the discovery of antibody dependent enhancement (ade) of ev71 infection illustrates the complex roles of antibody in controlling ev71 infection. in this study, to identify the distinct role of each igg subclass on neutralization and enhancement of ev ...201323700449
initial evidence on differences among enterovirus 71, coxsackievirus a16 and coxsackievirus b4 in binding to cell surface heparan sulphate.cell surface heparan sulphate (hs) mediates infection for many viruses from diverse families. we demonstrated significant antiviral potencies for a number of hs mimetics against a cloned strain of enterovirus 71 (ev71) in a previous study. thus, the involvement of hs in mediating viral infection of isolates of human enteroviruses was investigated in vero and human neural cells in the present work. in both cell lines, heparin and pentosan polysulphate significantly inhibited both infection and at ...201325674594
rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.the development of vaccines against infectious diseases represents one of the most important contributions to medical science. however, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. the biomimetic nucleating p ...201323589862
children of rural-to-urban migrant workers in china are at a higher risk of contracting severe hand, foot and mouth disease and ev71 infection: a hospital-based study.the incidence and severity of hand, foot and mouth disease have increased in mainland china since 2008. therapies and vaccines are currently at different stages of development. this study aimed to determine the social factors associated with the outbreaks and severity of the disease in chinese children. a multicentre, prospective, case-controlled study was conducted in shanghai, chongqing, guangzhou and shantou to identify the sociodemographic and behavioural risk factors for hand, foot and mout ...201326038441
heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy.although several factors participating in enterovirus 71 (ev71) entry and replication had been reported, the precise mechanisms associated with these events are far from clear. in the present study, we showed that heat shock protein 90 (hsp90) is a key element associated with ev71 entry and replication in a human rhabdomyosarcoma of rd cells. inhibition of hsp90 by pretreating host cells with hsp90β sirna or blocking hsp90 with a hsp90-specific antibody or geldanamycin (ga), a specific inhibitor ...201324098578
human microrna hsa-mir-296-5p suppresses enterovirus 71 replication by targeting the viral genome.enterovirus 71 (ev71) has emerged as a major cause of neurological disease following the near eradication of poliovirus. accumulating evidence suggests that mammalian micrornas (mirnas), a class of noncoding rnas of 18 to 23 nucleotides (nt) with important regulatory roles in many cellular processes, participate in host antiviral defenses. however, the roles of mirnas in ev71 infection and pathogenesis are still unclear. here, hsa-mir-296-5p expression was significantly increased in ev71-infecte ...201323468506
mda5 plays a crucial role in enterovirus 71 rna-mediated irf3 activation.induction of type-i interferons (ifns), ifn-α/β, is crucial to innate immunity against rna virus infection. cytoplasmic retinoic acid-inducible gene i (rig-i)-like receptors, including rig-i and melanoma differentiation-associated gene 5 (mda5), are critical pathogen sensors for activation of type-i ifn expression in response to rna virus infection. mda5 is required for type-i ifn expression in mouse models in response to infection by picornaviruses, such as encephalomyocarditis virus (emcv) and ...201323650567
inhibition of enveloped viruses infectivity by curcumin.curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (ha) activity. this study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. in all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. in contrast, the nonenveloped enterovirus 71 r ...201323658730
a laboratory evaluation of medicinal herbs used in china for the treatment of hand, foot, and mouth disease.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the causative agents of hand, foot, and mouth disease (hfmd). during recent epidemics of hfmd in china, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. there have been no microbiological studies to validate their usefulness for hfmd. we selected 12 commonly used herbs for hfmd from government recommended guidelines as well as published reports and tested fo ...201323554831
protective efficacy of vp1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human scarb2-transgenic mice.hand-foot-mouth diseases (hfmd) caused by enterovirus 71 (ev71) and coxsackievirus 16 (cva16) in children have now become a severe public health issue in the asian-pacific region. recently we have successfully developed transgenic mice expressing human scavenger receptor class b member 2 (hscarb2, a receptor of ev71 and cva16) as an animal model for evaluating the pathogenesis of enterovirus infections. in this study, hscarb2-transgenic mice were used to investigate the efficacy conferred by a p ...201323936115
formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of h5n1/ev71/jev.combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (h5n1/h1n1), enterovirus 71 (ev71), and/or japanese encephalitis virus (jev) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. we demonstrated that the antigeni ...201323838466
enterovirus 2apro targets mda5 and mavs in infected cells.rig-i-like receptors (rlrs) mda5 and rig-i are key players in the innate antiviral response. upon recognition of viral rna, they interact with mavs, eventually inducing type i interferon production. the interferon induction pathway is commonly targeted by viruses. how enteroviruses suppress interferon production is incompletely understood. mda5 has been suggested to undergo caspase- and proteasome-mediated degradation during poliovirus infection. additionally, mavs is reported to be cleaved duri ...201424390337
ev71 vaccine, an invaluable gift for children.enterovirus 71 (ev71) is a major pathogen for severe hand, foot and mouth disease (hfmd). development of vaccines against ev71 would be the most effective approach to prevent the ev71 outbreak. research and development (r&d) of ev71 vaccine was carried out in several asian countries. currently three companies in mainland china have completed phase iii clinical trials of inactivated ev71 whole-virus vaccines, whereas the other two companies have completed phase i clinical trials separately in tai ...201425505956
in vivo time-related evaluation of a therapeutic neutralization monoclonal antibody against lethal enterovirus 71 infection in a mouse model.enterovirus 71 (ev71) is a neurotropic virus capable of inducing severe neurological symptoms and death. no direct targeting antivirals are useful in the treatment of severe ev71 infection. because of low toxicity and good specificity, monoclonal antibodies (mab) are a potential candidate for the treatment of viral infections. therefore, we developed an ev71-specific conformational mab with high in vitro cross-neutralization activity to heterologous ev71 subgenotypes. the in vivo treatment exper ...201425279734
a cytoplasmic rna virus generates functional viral small rnas and regulates viral ires activity in mammalian cells.the roles of virus-derived small rnas (vsrnas) have been studied in plants and insects. however, the generation and function of small rnas from cytoplasmic rna viruses in mammalian cells remain unexplored. this study describes four vsrnas that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. viral infection produced substantial levels (>10(5) copy numbers per cell) of vsrna1, one of the four vsrnas. we also demonstrated that dicer is involved in ...201425352551
protease 2a induces stress granule formation during coxsackievirus b3 and enterovirus 71 infections.stress granules (sgs) are granular aggregates in the cytoplasm that are formed under a variety of stress situations including viral infection. previous studies indicate that poliovirus, a member of picornaviridae, can induce sg formation. however, the exact mechanism by which the picornaviruses induce sg formation is unknown.201425410318
parallel mrna and microrna profiling of hev71-infected human neuroblastoma cells reveal the up-regulation of mir-1246 in association with dlg3 repression.human enterovirus 71 (hev71) has emerged as the leading cause of viral encephalitis in children in most asian countries. the roles of host mirnas in the neurological pathogenesis of hev71 infection remain unknown. in the present study, comprehensive mirna expression profiling in hev71-infected human neuroblastoma sh-sy5y cells was performed using the affymetrix gene chip microarray assay and was validated using real-time rt-pcr. among the 69 differentially expressed mirnas, mir-1246 was specific ...201424739954
inhibition of enterovirus 71 replication by 7-hydroxyflavone and diisopropyl-flavon7-yl phosphate.enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease, which has been continuously prevalent in asia in recent years. in children, severe cases can lead to death, and no prophylactic or therapeutic measures against ev71 infection are available. the 3c proteases of ev71 play an important role in viral replication and are an ideal drug target. in previous work, we resolved the crystal structure for ev71 3cpro. in this report, we took advantage of the automated docking ...201424664133
anti-enterovirus 71 effects of chrysin and its phosphate ester.enterovirus 71 (ev71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. the anti-ev71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. by using the predicting program autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3cpro activity. replication of viral rna and production of viral capsid protein and the infect ...201424598537
er stress, autophagy, and rna viruses.endoplasmic reticulum (er) stress is a general term for representing the pathway by which various stimuli affect er functions. er stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (upr), which compromises the stimulus and then determines whether the cell survives or dies. in recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors ...201425140166
curcumin inhibits the replication of enterovirus 71 in vitro.human enterovirus 71 (ev71) is the main causative pathogen of hand, foot, and mouth disease (hfmd) in children. the epidemic of hfmd has been a public health problem in asia-pacific region for decades, and no vaccine and effective antiviral medicine are available. curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. in this study, we demonstrated that curcumin showed potent antiviral effect again ev71. in vero cells infected ...201426579397
enterovirus-71 virus-like particles induce the activation and maturation of human monocyte-derived dendritic cells through tlr4 signaling.enterovirus 71 (ev71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. we recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with ev71 virus-like particles (vlps), with a morphology resembling that of infectious ev71 virions but not containing a viral genome, which could potentially be safe as a vaccine for ev71. to elucidate the mechanisms through which ev71 vlps induce cell-med ...201425360749
[sequence analysis of vp1 region of coxsackievirus a4 and coxsackievirus a10 in guangzhou city, 2010-2012].to identify the enterovirus from stool samples of patients with hand, foot and mouth disease(hfmd) in guangzhou from 2010 to 2012 and to perform phylogenetic analysis of the vp1 gene sequences of coxsackievirus a4 and coxsackievirus a10.201425219430
prospect and challenges for the development of multivalent vaccines against hand, foot and mouth diseases.enterovirus 71 (ev71), an emerging neurotropic virus and coxsackieviruses (cv) are the major causative agents of hand, foot and mouth diseases (hfmd). these viruses have become a serious public health threat in the asia pacific region. formalin-inactivated ev71 (fi-ev71) vaccines have been developed, evaluated in human clinical trials and were found to elicit full protection against ev71. their failure to prevent cva16 infections could compromise the acceptability of monovalent ev71 vaccines. bi ...201425218294
changing aetiology of hand, foot and mouth disease in linyi, china, 2009-2011.millions of hand, foot and mouth disease cases occur annually and the disease is considered a significant public health threat in china. we have focused on linyi for 3 years to analyse the aetiological spectrum and epidemic changes. the reported number of cases of hfmd in linyi declined in 2011,with the percentage of hev71 dropping to 11%. although cva16 rose to 51% in 2011, the number of cva16 cases did not change significantly compared with the previous 2 years. other types of enteroviruses we ...201423910234
molecular epidemiology of enterovirus 71, coxsackievirus a16 and a6 associated with hand, foot and mouth disease in spain.hand, foot and mouth disease (hfmd) is a childhood illness frequently caused by genotypes belonging to the enterovirus a species, including coxsackievirus (cv)-a16 and enterovirus (ev)-71. between 2010 and 2012, several outbreaks and sporadic cases of hfmd occurred in different regions of spain. the objective of the present study was to describe the enterovirus epidemiology associated with hfmd in the country. a total of 80 patients with hfmd or atypical rash were included. detection and typing ...201424033818
a virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus a16 infections in mice.enterovirus 71(ev71) and coxsackievirus a16 (ca16) are responsible for hand, foot and mouth disease which has been prevalent in asia-pacific regions, causing significant morbidity and mortality in young children. co-circulation of and co-infection by both viruses underscores the importance and urgency of developing vaccines against both viruses simultaneously. here we report the immunogenicity and protective efficacy of a bivalent combination vaccine comprised of ev71 and ca16 virus-like particl ...201424950363
correlation analysis of ev71 detection and case severity in hand, foot, and mouth disease in the hunan province of china.an increase in the incidence of hand, foot and mouth disease (hfmd) cases has been observed in the hunan province of mainland china since 2009 with a particularly higher level of severe cases in 2010-2012. intestinal viruses of the picornaviridae family are responsible for the human syndrome associated with hfmd with enterovirus 71 (ev71) and coxsackievirus a16 (cox a16) being the most common causative strains. hfmd cases associated with ev71 are generally more severe with an increased associati ...201424941257
a combination vaccine comprising of inactivated enterovirus 71 and coxsackievirus a16 elicits balanced protective immunity against both viruses.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are the two major causative agents of hand, foot and mouth disease (hfmd), which is an infectious disease frequently occurring in children. a bivalent vaccine against both ev71 and ca16 is highly desirable. in the present study, we compare monovalent inactivated ev71, monovalent inactivated ca16, and a combination vaccine candidate comprising of both inactivated ev71 and ca16, for their immunogenicity and in vivo protective efficacy. the two mo ...201424657161
improved detection limit in rapid detection of human enterovirus 71 and coxsackievirus a16 by a novel reverse transcription-isothermal multiple-self-matching-initiated amplification assay.rapid detection of human enterovirus 71 (ev71) and coxsackievirus a16 (cva16) is important in the early phase of hand-foot-and-mouth disease (hfmd). in this study, we developed and evaluated a novel reverse transcription-isothermal multiple-self-matching-initiated amplification (rt-imsa) assay for the rapid detection of ev71 and cva16 by use of reverse transcriptase, together with a strand displacement dna polymerase. real-time rt-imsa assays using a turbidimeter and visual rt-imsa assays to det ...201424648558
new coxsackievirus b4 genotype circulating in inner mongolia autonomous region, china.hand, foot, and mouth disease (hfmd) surveillance was initiated in the inner mongolia autonomous region of china in 2007, a crucial scrutiny for monitoring the prevalence of enterovirus serotypes associated with hfmd patients. however, this surveillance mostly focused on enterovirus 71 (ev-a71) and coxsackievirus a16; therefore, information on other enterovirus serotypes is limited. to identify the other circulating enterovirus serotypes in the hfmd outbreaks in inner mongolia in 2010, clinical ...201424595311
coxsackievirus a16: epidemiology, diagnosis, and vaccine.coxsackievirus 16 (ca16) is one of the major pathogens associated with hand, foot, and mouth disease (hfmd) in infants and young children. in recent years, ca16 and human enterovirus 71 (ev71) have often circulated alternatively or together in the western pacific region, which has become an important public health problem in this region. hfmd caused by ca16 infection is generally thought to be mild and self-limiting. however, recently several severe and fatal cases involving ca16 have been repor ...201424231751
Refresh
firstprev
...111213141516171819
nextlast
Displaying items 1001 - 1100 of 1831