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enterovirus-specific anti-peptide antibodies.enterovirus 71 (ev-71) is the main causative agent of hand, foot, and mouth disease (hfmd) which is generally regarded as a mild childhood disease. in recent years, ev71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in asia. a formalin-inactivated ev71 whole virus vaccine has completed phase iii trial in china but is currently unavailable clinically. the high cost of manufacturing and supply problems may limit p ...201526424285
epidemiological characteristics and spatial-temporal clusters of hand, foot, and mouth disease in zhejiang province, china, 2008-2012.hand, foot and mouth disease (hfmd) is one of the major public health concerns in china. being the province with high incidence rates of hfmd, the epidemiological features and the spatial-temporal patterns of zhejiang province were still unknown. the objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. the surveillance data of hfmd during 2008-2012 were collected from the communicable disea ...201526422015
cellular proteome alterations in response to enterovirus 71 and coxsackievirus a16 infections in neuronal and intestinal cell lines.hand, foot and mouth disease is mainly caused by enterovirus a71 (ev-a71) and coxsackievirus a16 (cv-a16), but ev-a71 is also associated with severe neurological complications. host factors may contribute to the different clinical outcomes of ev-a71 and cv-a16 infections. a neurovirulent ev-a71 strain (ev-a71/uh1) from a fatal case, a non-neurovirulent ev-a71 strain (ev-a71/sha66) and a cv-a16 strain (cv-a16/22159) from cases of uncomplicated hfmd were used. replication of the viruses in sk-n-mc ...201526003530
the epidemiological study of coxsackievirus a6 revealing hand, foot and mouth disease epidemic patterns in guangdong, china.enterovirus a71 (eva71) and coxsackievirus a16 (cva16) are regarded as the two major causative pathogens in hand, foot and mouth disease (hfmd) epidemics. however, cva6, previously largely ignored, became the predominant pathogen in china in 2013. in this study, we describe the epidemiological trends of cva6 during the annual hfmd outbreaks from 2008 to 2013 in guangdong, china. the study results show that cva6 has been one of three major causative agents of hfmd epidemics since 2009. the period ...201525993899
type i interferons triggered through the toll-like receptor 3-trif pathway control coxsackievirus a16 infection in young mice.coxsackievirus a16 (cva16) is one of the major etiological agents of hand, foot, and mouth disease (hfmd) in children. the host defense mechanisms against cva16 infection remain almost entirely unknown. unlike previous observations with enterovirus 71 (ev71) infection, here we show that gamma interferon (ifn-γ) or invariant nk t cell deficiency does not affect disease development or the survival of cva16-infected mice. in contrast, type i interferon receptor deficiency resulted in the developmen ...201526292317
construction and characterization of an infectious cdna clone of echovirus 25.echovirus 25 (e-25) is a member of the enterovirus family and a common pathogen that induces hand, foot, and mouth disease (hfmd), meningitis, skin rash, and respiratory illnesses. in this study, we constructed and characterized an infectious full-length e-25 cdna clone derived from the xm0297 strain, which was the first subgenotype d6 strain isolated in xiamen, china. the 5'-untranslated regions (5'-utr), p3 (3a-3b, 3d) and p3 (3c) regions of this e-25 (xm0297) strain were highly similar to ev- ...201526004198
molecular epidemiology of an outbreak of hand, foot, and mouth disease associated with subgenotype c4a of enterovirus a71 in nanchang, china in 2014.an outbreak of hand, foot, and mouth disease was reported through hospital-based surveillance in nanchang, china in 2014. a total of 244 cases were reported, 176 (72.1%) cases were tested positive for enteroviruses by direct reverse transcription-polymerase chain reaction, in which enterovirus a71 (ev-a71), coxsackievirus a16 (cv-a16), and untyped enteroviruses (uev) accounted for 84.1%, 3.4%, and 12.5%, respectively. in this outbreak, children under 5 years old constituted more than 98% of the ...201526058813
time series analysis of reported cases of hand, foot, and mouth disease from 2010 to 2013 in wuhan, china.hand, foot, and mouth disease (hfmd) is an infectious disease caused by a group of enteroviruses, including coxsackievirus a16 (cva16) and enterovirus a71 (ev-a71). in recent decades, asian countries have experienced frequent and widespread hfmd outbreaks, with deaths predominantly among children. in several asian countries, epidemics usually peak in the late spring/early summer, with a second small peak in late autumn/early winter. we investigated the possible underlying association between the ...201526530702
a new ev71 vp3 epitope in norovirus p particle vector displays neutralizing activity and protection in vivo in mice.enterovirus 71 (ev71) and coxsackievirus a16 (cva16), as the main agents causing hand, foot and mouth disease (hfmd), have become a serious public health concern in the asia-pacific region. recently, various neutralizing b cell epitopes of ev71 were identified as targets for promising vaccine candidates. structural studies of picornaviridae indicated that potent immunodominant epitopes typically lie in the hypervariable loop of capsid surfaces. however, cross-neutralizing antibodies and cross-pr ...201526529072
potent antiviral agents fail to elicit genetically-stable resistance mutations in either enterovirus 71 or coxsackievirus a16.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the two major causative agents of hand, foot and mouth disease (hfmd), for which there are currently no licenced treatments. here, the acquisition of resistance towards two novel capsid-binding compounds, nld and ald, was studied and compared to the analogous compound gpp3. during serial passage, ev71 rapidly became resistant to each compound and mutations at residues i113 and v123 in vp1 were identified. a mutation at residue 113 was also ...201526522770
phylogenetic analysis of the major causative agents of hand, foot and mouth disease in suzhou city, jiangsu province, china, in 2012-2013.hand, foot and mouth disease (hfmd) is a serious public health problem that has emerged over the past several decades. pathogen detection by the chinese national hfmd surveillance system has focused mainly on enterovirus 71 (ev71) and coxsackievirus a16 (ca16). therefore, epidemiological information regarding the other causative enteroviruses is limited. to identify the pandemic enterovirus in suzhou, jiangsu province, china, clinical samples from patients with hfmd were collected from 2012 to 2 ...201526038764
seroepidemiology of coxsackievirus a6, coxsackievirus a16, and enterovirus 71 infections among children and adolescents in singapore, 2008-2010.coxsackieviruses a6 (cv-a6) and a16 (cv-a16) and enterovirus 71 (ev-a71) have caused periodic epidemics of hand, foot and mouth disease (hfmd) among children in singapore. we conducted a cross-sectional study to estimate the seroprevalence of these enteroviruses among singapore children and adolescents. the study was conducted between august 2008 and july 2010. it involved 700 singapore residents aged 1-17 years whose residual sera were obtained following the completion of routine biochemical in ...201526011735
enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated enterovirus a71 vaccine in jiangsu, china, 2012-2013.epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. an active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in jiangsu province from 2012 to 2013. fifty-nine infants were randomly selected from 522 non-ev-a71/cv-a16 hfmd patients. we collected 173 throat swabs and 174 rectal swabs from these infants. rt-pcr was used to ampl ...201526010334
risk factors for severe hand, foot and mouth disease.we studied risk factors associated with severe hand, foot and mouth disease (hfmd) caused by enteroviruses among patients aged less than 15 years admitted to king narai hospital, lopburi, thailand during 2011-2013. cases were divided into either mild or severe. severe cases were those with encephalitis, meningitis, myocarditis, pneumonia, pulmonary edema or respiratory failure. risk factors for severe infection were evaluated using univariate and multivariate logistic regression analysis. one hu ...201526521518
structure elucidation of coxsackievirus a16 in complex with gpp3 informs a systematic review of highly potent capsid binders to enteroviruses.the replication of enterovirus 71 (ev71) and coxsackievirus a16 (cva16), which are the major cause of hand, foot and mouth disease (hfmd) in children, can be inhibited by the capsid binder gpp3. here, we present the crystal structure of cva16 in complex with gpp3, which clarifies the role of the key residues involved in interactions with the inhibitor. based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders nld and ald, whi ...201526485389
the fecal virome of children with hand, foot, and mouth disease that tested pcr negative for pathogenic enteroviruses.hand, foot, and mouth disease (hfmd) affects infant and young children. a viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 thai children with clinical diagnosis of hfmd collected during the 2012 outbreak. these children had previously tested negative by pcr for enterovirus 71 and coxsackievirus a16 and a6. deep sequencing revealed nine virus families: picornaviridae, astroviridae, parvoviridae, caliciviridae, paramyxoviridae, adenoviridae, reovirida ...201526288145
structures of coxsackievirus a16 capsids with native antigenicity: implications for particle expansion, receptor binding, and immunogenicity.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the primary causes of the epidemics of hand-foot-and-mouth disease (hfmd) that affect more than a million children in china each year and lead to hundreds of deaths. although there has been progress with vaccines for ev71, the development of a cva16 vaccine has proved more challenging, and the ev71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. the structur ...201526269176
optimization and characterization of candidate strain for coxsackievirus a16 inactivated vaccine.coxsackievirus a16 (ca16) and enterovirus 71 (ev71), both of which can cause hand, foot and mouth disease (hfmd), are responsible for large epidemics in asian and pacific areas. although inactivated ev71 vaccines have completed testing in phase iii clinical trials in mainland china, ca16 vaccines are still under development. a vero cell-based inactivated ca16 vaccine was developed by our group. screening identified a ca16 vaccine strain (cc024) isolated from hfmd patients, which had broad cross- ...201526193302
[prevalence and analyses of the changing etiology of hand, foot and mouth disease in china].hand, foot, and mouth disease (hfmd) is a viral infectious disease regarded to be a public-health problem worldwide. since the 1990s, hfmd began to spread in the asia-pacific region (especially in south-east asia). hfmd outbreaks have occurred in mainland china frequently since 2008, and the morbidity and mortality of hfmd has continued to increase in recent years. in mainland china, enterovirus a serotype enterovirus a71 (ev-a71) and coxsackievirus a16 (cva16) have been the major pathogens of h ...201526738295
coxsackievirus a6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are the predominant pathogens causing outbreaks of hand, foot and mouth disease (hfmd) worldwide. other human enterovirus a (hev-a) serotypes tend to cause only sporadic hfmd cases. however, since a hfmd caused by coxsackievirus a6 broke out in finland in 2008, ca6 has been identified as the responsible pathogen for a series of hfmd outbreaks in europe, north america and asia. because of the severity of the clinical manifestations and the under ...201526112307
[pathogenic and clinical presentation of bullous rash in hand, foot and mouth disease].to investigate the pathogenic and clinical presentation and laboratory tests of bullous rash in hand, foot and mouth disease (hfmd) in xi'an from january 2013 to december 2014 by retrospective analysis.201526717661
clinical and etiological characteristics of atypical hand-foot-and-mouth disease in children from chongqing, china: a retrospective study.hand-foot-and-mouth disease (hfmd) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. to date, no study has been conducted to report the clinical and epidemiological characteristics of atypical hfmd.201526693489
prevalence of coxsackievirus a6 and enterovirus 71 in hand, foot and mouth disease in nanjing, china in 2013.although hand, foot and mouth disease (hfmd) has been strongly associated with enterovirus 71 (ev71), coxsackievirus a16 (cva16) and other enteroviruses, studies regarding coxsackievirus a6 (cva6) infection in hfmd are limited. the aim of this study was to identify the major etiological agents causing hfmd in nanjing in 2013 and explore the clinical and genetic characteristics of the prevalent enterovirus (ev) types in hfmd.201526090576
efficacy of a trivalent hand, foot, and mouth disease vaccine against enterovirus 71 and coxsackieviruses a16 and a6 in mice.hand, foot, and mouth disease (hfmd) has recently emerged as a major public health concern across the asian-pacific region. enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the primary causative agents of hfmd, but other members of the enterovirus a species, including coxsackievirus a6 (cva6), can cause disease. the lack of small animal models for these viruses have hampered the development of a licensed hfmd vaccine or antivirals. we have previously reported on the development of a mous ...201526593938
[research progress on seroepidemiological study of enterovirus 71 and coxsackievirus a16 infection among children].most common causative agents for hand, foot and mouth disease (hfmd) are enterovirus 71 (ev-a71) and coxsackievirus a16 (cv-a16). the symptomatic and asymptomatic cases could transmit the disease in population. many sero-epidemiological surveys were launched to estimate the sero-incidence of ev-a71 and cv-a16 enterovirus, the susceptibility of different sub-population, and to observe the dynamics of neutralizing antibody. a literature search of sero-epidemiological study focused on ev-a71 or cv- ...201526081408
the antiviral and antimicrobial activities of licorice, a widely-used chinese herb.licorice is a common herb which has been used in traditional chinese medicine for centuries. more than 20 triterpenoids and nearly 300 flavonoids have been isolated from licorice. recent studies have shown that these metabolites possess many pharmacological activities, such as antiviral, antimicrobial, anti-inflammatory, antitumor and other activities. this paper provides a summary of the antiviral and antimicrobial activities of licorice. the active components and the possible mechanisms for th ...201526579460
[infection status of enterovirus 71 and coxsackievirus a16 among children receiving health examination for child care setting entrance in beijing and their related medical care seeking practice].to understand the infection status of enterovirus 71 (ev71) and coxsackievirus a16 (cox a16) among children receiving health examination for child care setting entrance in beijing and their related medical care seeking practice and provide evidence for the estimation of disease burden caused by hand foot and mouth disease (hfmd).201526564703
etiology of multiple non-ev71 and non-cva16 enteroviruses associated with hand, foot and mouth disease in jinan, china, 2009-june 2013.hand, foot, and mouth disease (hfmd) is an infectious disease caused by human enterovirus 71 (ev71), coxsackievirus a16 (cva16) and other enteroviruses. it is of interest that other enteroviruses associated with hfmd in jinan have been rarely reported. the aim of the present study is to detect and characterize the circulating serotypes of non-ev71 and non-cva16 enteroviruses associated with hfmd in jinan city, shandong province, china. a total of 400 specimens were collected from clinically diag ...201526562154
itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein.itraconazole (itz) is a well-known antifungal agent that also has anticancer activity. in this study, we identify itz as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus). we demonstrate that itz inhibits viral rna replication by targeting oxysterol-binding protein (osbp) and osbp-related protein 4 (orp4). consistently, osw-1, a specific osbp/orp4 antagonist, also inhibits enterovirus replication. knockdown of osbp inhibits virus replicati ...201525640182
expression of enterovirus 71 virus-like particles in transgenic enoki (flammulina velutipes).no commercial vaccines are currently available for enterovirus 71 (ev71) infection. oral virus-like particle (vlp) vaccines are regarded as a better choice for prevention from food-borne diseases compared with injected whole virus vaccines. unfortunately, the application of oral vlp vaccines produced from transgenic plants was limited due to the concerns of gene contamination. alternatively, using transgenic mushrooms retains the advantages of transgenic plants and tremendously reduce risks of g ...201525957149
hexon-modified recombinant e1-deleted adenoviral vectors as bivalent vaccine carriers for coxsackievirus a16 and enterovirus 71.hand, foot and mouth disease (hfmd) is a major public health concern in asia; more efficient vaccines against hfmd are urgently required. adenoviral (ad) capsids have been used widely for the presentation of foreign antigens to induce specific immune responses in the host. here, we describe a novel bivalent vaccine for hfmd based on the hexon-modified, e1-deleted chimpanzee adenovirus serotype 68 (adc68). the novel vaccine candidate was generated by incorporating the neutralising epitope of coxs ...201526296491
recombinant adeno-vaccine expressing enterovirus 71-like particles against hand, foot, and mouth disease.enterovirus 71 (ev71) and coxsackieviruses (cv) are the major causative agents of hand, foot and mouth disease (hfmd). there is not currently a vaccine available against hfmd, even though a newly developed formalin-inactivated ev71 (fi-ev71) vaccine has been tested in clinical trial and has shown efficacy against ev71. we have designed and genetically engineered a recombinant adenovirus ad-evvlp with the ev71 p1 and 3cd genes inserted into the e1/e3-deleted adenoviral genome. ad-evvlp were produ ...201525855976
microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse-transcription polymerase chain reaction for the rapid detection of enterovirus 71 and coxsackievirus a16 in throat swab specimens.enterovirus 71 and coxsackievirus a16 are the main pathogens causing hand-foot-mouth disease. in this paper, microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse transcript-polymerase chain reaction has been developed for the detection of enterovirus 71 and coxsackievirus a16 in throat swab specimens. the specific reverse transcription-polymerase chain reaction amplicons labeled with sybr orange were separated by microchip capillary electropho ...201525953405
characterization of severe hand, foot, and mouth disease in shenzhen, china, 2009-2013.hand, foot, and mouth disease (hfmd) is caused by human enteroviruses, especially by enterovirus 71 (ev71) and coxsackievirus a16 (ca16). patients infected with different enteroviruses show varied clinical symptoms. the aim of this study was to determine whether the etiological spectrum of mild and severe hfmd changed, and the association between pathogens and clinical features. from 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. a dynami ...201525951788
comparative pathogenicity of coxsackievirus a16 circulating and noncirculating strains in vitro and in a neonatal mouse model.an enterovirus 71 (ev71) vaccine for the prevention of hand, foot, and mouth disease (hmfd) is available, but it is not known whether the ev71 vaccine cross-protects against coxsackievirus (cv) infection. furthermore, although an inactivated circulating cva16 changchun 024 (cc024) strain vaccine candidate is effective in newborn mice, the cc024 strain causes severe lesions in muscle and lung tissues. therefore, an effective cv vaccine with improved pathogenic safety is needed. the aim of this st ...201525831207
crystal structures of enterovirus 71 (ev71) recombinant virus particles provide insights into vaccine design.hand-foot-and-mouth disease (hfmd) remains a major health concern in the asia-pacific regions, and its major causative agents include human enterovirus 71 (ev71) and coxsackievirus a16. a desirable vaccine against hfmd would be multivalent and able to elicit protective responses against multiple hfmd causative agents. previously, we have demonstrated that a thermostable recombinant ev71 vaccine candidate can be produced by the insertion of a foreign peptide into the bc loop of vp1 without affect ...201525492868
towards broadly protective polyvalent vaccines against hand, foot and mouth disease.hand, foot, and mouth disease (hfmd) caused by multiple enterovirus infections is a serious health threat to children in the asia-pacific region. this article reviews progresses in the development of vaccines for hfmd and discusses the need for polyvalent hfmd vaccines for conferring broad-spectrum protection.201525449959
review of enterovirus 71 vaccines.enterovirus 71 (ev71) and coxsackieviruses are the major causative agents of hand, foot, and mouth disease (hfmd) outbreaks worldwide and have a significant socioeconomic impact, particularly in asia. formalin-inactivated (fi) ev71 vaccines evaluated in human clinical trials in china, taiwan, and singapore were found to be safe and to elicit strong neutralizing antibody responses against ev71 currently circulating in asia. the results from 3 different phase 3 clinical trials performed in young c ...201525352588
dynamic constitution of the pathogens inducing encephalitis in hand, foot and mouth disease in kunming, 2009-2011.hand, foot and mouth disease (hfmd), caused by various viral pathogens, is an emerging infectious disease in children in asia. understanding the composition of these pathogens is necessary to prevent and control this disease. in the present study, the pathogens in 436 hfmd patients (from 2009 to 2011) with concurrent clinical indications of encephalitis, meningoencephalitis, or both, were defined using the semi-nested pcr. a systematic analysis of the composition of these pathogens was performed ...201525866107
crystal structures of yeast-produced enterovirus 71 and enterovirus 71/coxsackievirus a16 chimeric virus-like particles provide the structural basis for novel vaccine design against hand-foot-and-mouth disease.human enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the two major causative agents for hand-foot-and-mouth disease (hfmd). previously, we demonstrated that a virus-like particle (vlp) for ev71 produced from saccharomyces cerevisiae is a potential vaccine candidate against ev71 infection, and an ev71/cva16 chimeric vlp can elicit protective immune responses against both virus infections. here, we presented the crystal structures of both vlps, showing that both the linear and conformati ...201525833050
ev71 vaccines: a first step towards multivalent hand, foot and mouth disease vaccines.enterovirus a infections are the primary cause of hand, foot and mouth disease in infants and young children. enterovirus 71 (ev71) and coxsackievirus a16 have emerged as neurotropic viruses responsible for severe neurological complications and a serious public health threat across the asia-pacific region. formalin-inactivated ev71 vaccines have elicited protection against ev71 but not against coxsackievirus a16 infections. the development of a bivalent formalin-inactivated ev71/fi coxsackieviru ...201525536888
antiviral activity of paulownia tomentosa against enterovirus 71 of hand, foot, and mouth disease.the bark, leaves, and flowers of paulownia trees have been used in traditional chinese medicine to treat infectious and inflammatory diseases. we investigated the antiviral effects of paulownia tomentosa flowers, an herbal medicine used in some provinces of p. r. china for the treatment of skin rashes and blisters. dried flowers of p. tomentosa were extracted with methanol and tested for antiviral activity against enterovirus 71 (ev71) and coxsackievirus a16 (cav16), the predominant etiologic ag ...201525744451
novel recombinant chimeric virus-like particle is immunogenic and protective against both enterovirus 71 and coxsackievirus a16 in mice.hand-foot-and-mouth disease (hfmd) has been recognized as an important global public health issue, which is predominantly caused by enterovirus 71 (ev-a71) and coxsackievirus a16 (cva16). there is no available vaccine against hfmd. an ideal hfmd vaccine should be bivalent against both ev-a71 and cva16. here, a novel strategy to produce bivalent hfmd vaccine based on chimeric ev-a71 virus-like particles (chiev-a71 vlps) was proposed and illustrated. the neutralizing epitope sp70 within the capsid ...201525597595
antiviral effects of phyllanthus urinaria containing corilagin against human enterovirus 71 and coxsackievirus a16 in vitro.human enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are major causative agents of hand, foot, and mouth disease (hfmd) especially in infants and children under 5 years of age. despite recent outbreaks of hfmd, there are no approved therapeutics against ev71 and ca16 infection. moreover, in a small percentage of cases, the disease progression can lead to serious complications of the central nervous system. in this study, we investigated the antiviral effect of corilagin and phyllanthus urin ...201524752860
the compatibility of inactivated-enterovirus 71 vaccination with coxsackievirus a16 and poliovirus immunizations in humans and animals.enterovirus 71 (ev71) is the key pathogen for hand, foot, and mouth disease (hfmd) and can result in severe neurological complications and death among young children. three inactivated-ev71 vaccines have gone through phase iii clinical trials and have demonstrated good safety and efficacy. these vaccines will benefit young children under the threat of severe hfmd. however, the potential immunization-related compatibility for different enterovirus vaccines remains unclear, making it hard to inclu ...201525715318
molecular epidemiology of coxsackievirus a6 associated with outbreaks of hand, foot, and mouth disease in tianjin, china, in 2013.since 2008, mainland china has undergone widespread outbreaks of hand, foot, and mouth disease (hfmd). in order to determine the characteristics of epidemics and enteroviruses (ev) associated with hfmd in tianjin, in northern china, epidemiological and virological data from routine surveillance were collected and analyzed. in tianjin, a persistent epidemic of hfmd was demonstrated during 2008-2013, involving 102,705 mild, 179 severe, and 16 fatal cases. overall, 8234 specimens were collected fro ...201525680566
enterovirus 71 mediates cell cycle arrest in s phase through non-structural protein 3d.many viruses disrupt the host cell cycle to facilitate their own growth. we assessed the mechanism and function of enterovirus 71 (ev71), a primary causative agent for recent hand, foot, and mouth disease outbreaks, in manipulating cell cycle progression. our results suggest that ev71 infection induces s-phase arrest in diverse cell types by preventing the cell cycle transition from the s phase into the g2/m phase. similar results were observed for an alternate picornavirus, coxsackievirus a16. ...201525659038
two models for changes of ev71 immunity in infants and young children.human enterovirus 71 (ev71) has been associated with outbreaks of hand-foot-and-mouth disease (hfmd) in china. susceptibility to ev71 is associated with age, but few studies have been accomplished to measure such a relationship. a better understanding of the connection between susceptibility and age is necessary to develop strategies for control of hfmd. in 2010, a survey of an epidemic of ev71 was conducted in a northern city of jiangsu province in china. samples were tested serologically to id ...201525906390
simultaneous point-of-care detection of enterovirus 71 and coxsackievirus b3.human enterovirus 71 (ev71) is one of the pathogens that causes hand, foot, and mouth disease (hfmd), which generally leads to neurological diseases and fatal complications among children. since the early clinical symptoms from ev71 infection are very similar to those from coxsackievirus b3 (cvb3) infection, a robust and sensitive detection method that can be used to distinguish ev71 and cvb3 is urgently needed for prompting medical treatment of related diseases. herein, based on immunomagnetic ...201526461918
the c terminus of the core β-ladder domain in japanese encephalitis virus nonstructural protein 1 is flexible for accommodation of heterologous epitope fusion.ns1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (er), where ns1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. here, by using a trans-complementation assay, we identified the c-terminal end of ns1 derived from japanese encephalitis virus (jev), which ...201526559836
combination of intratypic and intertypic recombinant events in ev71: a novel evidence for the "triple-recombinant" strains of genotype a viruses in mainland china from 2008 to 2010.the first enterovirus 71 (ev71) strain isolated in 1969 was classified as genotype a. it is interesting that the genotype a disappeared nearly 40 years until its re-emergence in mainland china in 2008-2010. few studies on genetic characterization of the re-emerged genotype a viruses have been reported. in this study, a series of analyses were performed on molecular epidemiology and genome recombination of genotype a viruses in china. phylogenetic analysis indicated that except for 17 reported ge ...201525724176
synergistic antiviral activity of gemcitabine and ribavirin against enteroviruses.enteroviruses are major causative agents of various human diseases, and some of them are currently considered to be an enormous threat to public health. however, no effective therapy is currently available for the treatment of these infections. we identified gemcitabine, a nucleoside-analog drug used for cancer treatment, from a screen of bioactive chemicals as a novel inhibitor of coxsackievirus b3 (cvb3) and enterovirus 71 (ev71). gemcitabine potently inhibited the proliferation of cvb3 and ev ...201526526589
formononetin inhibits enterovirus 71 replication by regulating cox- 2/pge₂ expression.the activation of erk, p38 and jnk signal cascade in host cells has been demonstrated to up-regulate of enterovirus 71 (ev71)-induced cyclooxygenase-2 (cox-2)/ prostaglandins e2 (pge₂) expression which is essential for viral replication. so, we want to know whether a compound can inhibit ev71 infection by suppressing cox-2/pge₂ expression.201525890183
unusual skin manifestation of hand, foot and mouth disease associated with coxsackievirus a6: cases report.hand, food, and mouth disease (hfmd) is a highly contagious disease caused by enteroviruses infection. it is a health problem in young children under 5 years of age worldwide. the common causative agents are coxsackievirus a 16 (ca16) and enterovirus 71 (ev71). in recent years, coxsackievirus a6 (ca6) has emerged to be one of the major etiologic agents of hfmd worldwide including in thailand.201526203408
yakammaoto inhibits enterovirus 71 infection by reducing viral attachment, internalization, replication, and translation.enterovirus 71 (ev71) can cause central nervous system infections with mortality and neurologic sequelae. at present, there is no effective therapeutic modality for ev71 infection. the infection is more common in families with poor socioeconomic status. therefore, finding a readily available, cost-effective therapeutic modality would be very helpful to these socioeconomically disadvantaged families. yakammaoto is a cheap and readily available traditional prescription that is proven to have antiv ...201526043408
enhanced enterovirus 71 virus-like particle yield from a new baculovirus design.enterovirus 71 (ev71) is responsible for the outbreaks of hand-foot-and-mouth disease in the asia-pacific region. to produce the virus-like particle (vlp) vaccine, we previously constructed recombinant baculoviruses to co-express ev71 p1 polypeptide and 3cd protease using the bac-to-bac(®) vector system. the recombinant baculoviruses resulted in p1 cleavage by 3cd and subsequent vlp assembly in infected insect cells, but caused either low vlp yield or excessive vlp degradation. to tackle the pro ...201525997678
evaluation of a viral microarray based on simultaneous extraction and amplification of viral nucleotide acid for detecting human herpesviruses and enteroviruses.in this study, a viral microarray based assay was developed to detect the human herpesviruses and enteroviruses associated with central nervous system infections, including herpes simplex virus type 1, type 2 (hsv1 and hsv2), epstein-barr virus (ebv), cytomegalovirus (cmv), enterovirus 71 (ev71), coxsackievirus a 16 (ca16) and b 5(cb5). the dna polymerase gene of human herpesviruses and 5'-untranslated region of enteroviruses were selected as the targets to design primers and probes. human herpe ...201525774509
establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.the aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and imm ...201525263613
exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.the enterovirus genus of the picornaviridae is represented by several viral pathogens that are associated with human disease, namely poliovirus 1, enterovirus 71 and rhinoviruses. enterovirus 71 has been associated with encephalitis, while rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of rhinovirus replication.201526071135
the role of micrornas in enteroviral infections.the genus enterovirus, a member of the picornavirus family, are rna viruses that can cause poliomyelitis, hand-food-mouth disease, viral meningitis or meningoencephalitis, viral myocarditis and so on. micrornas are a class of highly conserved, small noncoding rnas recognized as important regulators of gene expression. recent studies found that micrornas play a significant role in the infection of enterovirus, such as enterovirus 71, coxsackievirus b3 and other enterovirus. enteroviral infection ...201526342975
antiviral activity of chrysin derivatives against coxsackievirus b3 in vitro and in vivo.chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (ev71) by suppressing viral 3c protease (3c(pro)) activity. in the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus b3 (cvb3), which belongs to the same genus (enterovirus) as ev71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. we found that chrysin showed antiviral activity against cvb3 at 10 μm, but exhibited mild ...201526336587
[the etiological and clinical characteristics of hospitalized children with hand, foot and mouth disease in beijing in 2013].to investigate the etiology of hand, foot and mouth disease (hfmd) in beijing during 2013, and study the clinical characteristics of hfmd caused by the main serotypes of enterovirus in the study.201526310558
the rna template channel of the rna-dependent rna polymerase as a target for development of antiviral therapy of multiple genera within a virus family.the genus enterovirus of the family picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. the viral rna-dependent rna polymerase is an attractive target for antiviral therapy. nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. most non-nucleoside inhibitors (nnis) target surface cavities, which are structurally more flexible than the nucleoti ...201525799064
rapid next-generation sequencing of dengue, ev-a71 and rsv-a viruses.accurate characterisation of viral strains constitutes a crucial objective for the management of modern virus collections. next-generation sequencing (ngs) provides technical solution for fast and cost-effective full genome sequencing. here, we report protocols for rapid full-genome characterisation of rna viruses of medical importance: dengue virus, enterovirus a71 and respiratory syncytial virus a, based on a specific amplification step followed by ngs-sequencing. a subset of full-length genom ...201526376168
mapping enterovirus a71 antigenic determinants from viral evolution.human enterovirus a71 (ev-a71) belongs to the enterovirus a species in the picornaviridae family. several vaccines against ev-a71, a disease causing severe neurological complications or even death, are currently under development and being tested in clinical trials, and preventative vaccination programs are expected to start soon. to characterize the potential for antigenic change of ev-a71, we compared the sequences of two antigenically diverse genotype b4 and b5 strains of ev-a71 and identifie ...201526339057
enterovirus a71 meningoencephalitis outbreak, rostov-on-don, russia, 2013.seventy-eight cases of enterovirus infection, including 25 neuroinfections, occurred in rostov-on-don, russia, during may-june 2013. the outbreak was caused by an enterovirus a type 71 (ev-a71) subgenotype c4 lineage that spread to neighboring countries from china ≈3 years earlier. enterovirus associated neuroinfection may emerge in areas with a preceding background circulation of ev-a71 with apparently asymptomatic infection.201526196217
analysis on the sequence of the whole genome of an isolated enterovirus 71 strain.an enterovirus 71 (ev71) strain query was isolated from a patient specimen in 2015. in order to known about its genetic evolution, this study amplified gene fragment of the isolated stain by rt-pct and carried out sequencing of the total genome. the homology and genetic evolution of the gene sequence of the virus strain in the study were analyzed. the results showed that the isolated ev71 strain in this study had higher homology of nucleotide sequence and amino acid sequence with other virus str ...201526884986
[analysis of seroepidemiology of enterovirus 71 diseases in children in jiangsu province].to analyze the dynamic pattern and the distributive characteristics of neutralizing antibody against enterovirus 71 (ev-a71 ) in children aged 6-35 months in jiangsu province from 2012 to 2014.201526887297
[expression and significance of toll-like receptors 7 and 8 in brain and lung tissues of death cases caused by ev71 infection].to study the significance of toll-like receptors (tlr) -7 and -8 in the pathogenesis of infection caused by enterovirus type 71 (ev71) through measuring the expression of tlr7 and tlr8 in brain and lung tissues from the death cases caused by ev71 infection.201526483222
analysis of ev71 infection progression using triple-silac-based proteomics approach.enterovirus 71 (ev71), a member of picornaviridae, causes severe neurological and systemic illness in children. to better understand the virus-host cell interactions, we performed a triple-silac-based quantitative proteomics study monitoring host cell proteome changes after ev71 infection. based on the quantitative data for more than 4100 proteins, ∼17% of the proteins were found as significantly changed (p<0.01) at either 8 or 20 hours post infection. five biological processes and seven protein ...201526306425
association of chemotactic chemokine ligand 5 polymorphisms with the risk of developing severe enterovirus 71 infection.respiratory damage is a main manifestation of severe enterovirus 71 (ev71) infection. polymorphisms of -403g/a (rs2107538), -28c/g (rs2280788), and in1.1t/c (rs2280789) in chemotactic chemokine ligand 5 (ccl5) have linked with many respiratory diseases. in this study, we explored the possible correlation of ccl5 polymorphisms with severe ev71 infection. blood samples were obtained from 87 children hospitalized for ev71 infection. fifty-seven healthy children were enrolled as asymptomatic control ...201526304916
complete genome sequence analysis of enterovirus 71 isolated from children with hand, foot, and mouth disease in thailand, 2012-2014.the complete genomic sequences of 14 enterovirus 71 (ev71) strains isolated from children with hand, foot, and mouth disease in thailand from 2012 to 2014 were determined and compared to enterovirus group a prototypes. phylogenetic analysis revealed that 13 strains resembled the b5 subgroup, while one strain from a fatal case designated tha_1219 belonged to the c4 subgroup. similarity plot and bootscan analyses suggested that tha_1219 underwent recombination in the p2 and p3 regions. full-genome ...201526303899
clinical features for mild hand, foot and mouth disease in china.mild hand, foot and mouth disease (hfmd) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. clinical diagnosis of mild hfmd was made by the presenting symptoms and signs (symptoms in brief) alone. we aim to evaluate the frequencies of symptoms in a retrospective case series study.201526302092
systematic review of economic evaluations of vaccination programs in mainland china: are they sufficient to inform decision making?the purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland china. we searched for economic evaluations of vaccination in china published prior to august 3, 2015 in eight english-language and three chinese-language databases. each article was appraised against the 19-item consensus on health economic criteria list (chec-list). we found 23 papers evaluating vaccines against hepatitis b (8 articles), streptococcus pneumoniae (5 articles), hu ...201526435189
the suramin derivative nf449 interacts with the 5-fold vertex of the enterovirus a71 capsid to prevent virus attachment to psgl-1 and heparan sulfate.nf449, a sulfated compound derived from the antiparasitic drug suramin, was previously reported to inhibit infection by enterovirus a71 (ev-a71). in the current work, we found that nf449 inhibits virus attachment to target cells, and specifically blocks virus interaction with two identified receptors--the p-selectin ligand, psgl-1, and heparan sulfate glycosaminoglycan--with no effect on virus binding to a third receptor, the scavenger receptor scarb2. we also examined a number of commercially a ...201526430888
a bivalent virus-like particle based vaccine induces a balanced antibody response against both enterovirus 71 and norovirus in mice.noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. genogroup ii.4 (gii.4) strains are responsible for the majority of norovirus outbreaks. enterovirus 71 (ev71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in asia-pacific regions, resulting in significant morbidity and mortality in young children. however, no vaccine is commercially availab ...201526424606
similar protective immunity induced by an inactivated enterovirus 71 (ev71) vaccine in neonatal rhesus macaques and children.during the development of enterovirus 71 (ev71) inactivated vaccine for preventing human hand, foot and mouth diseases (hfmd) by ev71 infection, an effective animal model is presumed to be significant and necessary. our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of hfmd, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during ev71 infection. althou ...201526419198
immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy chinese children: a report of further observations.to investigate the long-term effects on immunity of an inactivated enterovirus 71 (ev71) vaccine and its protective efficacy.201526381232
anti-enterovirus 71 agents of natural products.this review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. it covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. in total, 58 naturally-occurring anti-ev71 compounds are recorded.201526370955
seroprevalence of enterovirus 71 antibody among children in china: a systematic review and meta-analysis.hand, foot and mouth disease mostly affects children and carries a substantial disease burden in the western pacific region. enterovirus 71 (ev71) is the most virulent causative agent, and a monovalent vaccine against ev71 will soon become commercially available in china. an improved understanding of ev71 epidemiology would aid policy decisions regarding childhood immunization in china. we aimed to assess and summarize information to date from individual seroepidemiologic studies of ev71 in main ...201526368058
the role of vp1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a cynomolgus monkey model.enterovirus 71 (ev71), a major causative agent of hand, foot, and mouth disease, occasionally causes severe neurological symptoms. we identified p-selectin glycoprotein ligand-1 (psgl-1) as an ev71 receptor and found that an amino acid residue 145 in the capsid protein vp1 (vp1-145) defined psgl-1-binding (pb) and psgl-1-nonbinding (non-pb) phenotypes of ev71. however, the role of psgl-1-dependent ev71 replication in neuropathogenesis remains poorly understood. in this study, we investigated vir ...201526181772
broad protection with an inactivated vaccine against primary-isolated lethal enterovirus 71 infection in newborn mice.circulating enterovirus 71 (ev-a71)-associated hand, foot, and mouth disease is on the rise in the asian-pacific region. although animal models have been developed using mouse-adapted ev-a71 strains, mouse models using primary ev-a71 isolates are scarce. lethal animal models with circulating ev-a71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation.201526169371
[molecular mechanism of action of hnrnp k and rtn3 in the replication of enterovirus 71].enterovirus 71 (ev71) is a neurotropic pathogen that can induce hand, foot and mouth disease in children. there is an appreciable mortality rate after ev71 infections. the mechanism of action of ev71 replication is not known. recent work has identified some of cell factors of the host that participate in the synthesis of the rna and proteins of ev71 (e.g., hnrnp k, reticulon 3 (rtn 3)). in that work, researchers used a competitive assay to show that hnrnp k can interact with ev71 5' utr, which i ...201526164948
tia-1 and tiar interact with 5'-utr of enterovirus 71 genome and facilitate viral replication.enterovirus 71 is one of the major causative pathogens of hfmd in children. upon infection, the viral rna is translated in an ires-dependent manner and requires several host factors for effective replication. here, we found that t-cell-restricted intracellular antigen 1 (tia-1), and tia-1 related protein (tiar) were translocated from nucleus to cytoplasm after ev71 infection and localized to the sites of viral replication. we found that tia-1 and tiar can facilitate ev71 replication by enhancing ...201526363455
development of a specific latex agglutination test to detect antibodies of enterovirus 71.a latex agglutination test (lat) was developed for the rapid detection of antibodies against the vp1 or vp1 proteins of enterovirus 71 (ev71). the proteins of interest including prokaryotically expressed vp1 and two strains of anti-vp1 monoclonal antibody (mcab) against ev71 were covalently linked to carboxylated latex using ethyl-dimethyl-amino-propyl carbodiimide (edc) to prepare sensitized latex beads. lat was evaluated by an enzyme-linked immunosorbent assay (elisa) as a reference test. the ...201526363276
a severe case of co-infection with enterovirus 71 and vaccine-derived poliovirus type ii.enterovirus 71 (ev71) is often identified as the primary pathogen that directly leads to severe cases of hfmd, whereas the association between other enteroviruses and ev71 infection remains largely unclear. here we report a rare case of a 5-year-old boy co-infected with ev71 and vaccine-derived poliovirus (vdpv) type ii, which were identified based on pcr and sequence analysis results and clinical symptoms and were characterized on ct. we determined that the ev71 strain belongs to the c4 subtype ...201526361010
global quantitative proteomic analysis of human glioma cells profiled host protein expression in response to enterovirus type 71 infection.enterovirus 71 (ev71) is one of the leading causes of hand, foot and mouth disease with neurological complications in some cases. to study the pathogenesis of ev71 infection, large-scale analyses of ev71 infected cells have been performed. however, most of these studies employed rhabdomyosarcoma (rd) cells or used transcriptomic strategy. here, we performed silac-based quantitative proteomic analysis of ev71-infected u251 cells, a human glioma cell line. a total of 3125 host proteins were quanti ...201526350028
co-infection of enterovirus 71 and staphylococcus aureus in a 6-month-old male infant. 201526322107
replication and inhibitors of enteroviruses and parechoviruses.the enterovirus (ev) and parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, ev-a71, ev-d68, and human parechoviruses (hpev). they cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. at the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all evs and hpevs due to the great number o ...201526266417
intrinsic apoptosis and proinflammatory cytokines regulated in human astrocytes infected with enterovirus 71.enterovirus 71 (ev71) has emerged as a clinically important neurotropic virus following poliovirus eradication. however, the mechanism of ev71-induced neurological manifestation remains largely unclear. in this study, we showed that human astrocytes were susceptible to ev71 and viral rna was first detected at 12 h post-infection (p.i.), whilst viral proteins were detected at 36 h p.i. ev71-infected astrocytes underwent apoptosis, in which cytochrome c was released from mitochondria to the cytoso ...201526296773
nuclear protein sam68 interacts with the enterovirus 71 internal ribosome entry site and positively regulates viral protein translation.enterovirus 71 (ev71) recruits various cellular factors to assist in the replication and translation of its genome. identification of the host factors involved in the ev71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. in this study, we demonstrated that the cellular factor 68-kda src-associated protein in mitosis (sam68) acts as an internal ribosome entry site (ires) trans-ac ...201526202240
the antiviral effect of baicalin on enterovirus 71 in vitro.baicalin is a flavonoid compound extracted from scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. however, the antiviral effect of baicalin on enterovirus 71 (ev71) is still unknown. in this study, we found that baicalin showed inhibitory activity on ev71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. the expressions of ev71/3d mrna and polymerase were significantly blocked by ...201526295407
inactivated enterovirus 71 vaccine produced by 200-l scale serum-free microcarrier bioreactor system provides cross-protective efficacy in human scarb2 transgenic mouse.epidemics and outbreaks caused by infections of several subgenotypes of ev71 and other serotypes of coxsackie a viruses have raised serious public health concerns in the asia-pacific region. these concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. in this report, we present a platform for the large-scale production of a vaccine based on the inactivated ev71(e59-b4) virus. the ...201526287531
understanding enterovirus 71 neuropathogenesis and its impact on other neurotropic enteroviruses.enterovirus a71 (ev-a71) belongs to the species group a in the enterovirus genus within the picornaviridae family. ev-a71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. the pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. ev-a71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly ...201526276025
antibodies to p-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.p-selectin glycoprotein ligand-1 (psgl-1) has been proved to serve as the functional receptor for enterovirus 71 (ev71). we found the abundant expression of psgl-1 on monocyte-derived dendritic cells (mddcs). however, we have previously demonstrated that mddcs did not support efficient replication of ev71. dendritic cells (dcs) have been described to be subverted by various viruses including ev71 for viral dissemination, we thus explore the potential contribution of psgl-1 on dc-mediated ev71 tr ...201526399965
enterovirus 71 infection caused neuronal cell death and cytokine expression in cultured rat neural cells.fatal enterovirus type-71 (ev71) cases are associated with central nervous system infection characterized by inflammatory cell infiltration and activation, cytokine overproduction, and neuronal cell death. although ev71 antigen has been detected in neurons and glia, the molecular mechanisms underlying ev71-associated neuroinflammation and neuronal cell death are not fully understood. using cultured rodent neural cell models, we found that ev71 infection preferentially caused cell death in neuron ...201526399559
enterovirus 71 2c protein inhibits nf-κb activation by binding to rela(p65).viruses evolve multiple ways to interfere with nf-κb signaling, a key regulator of innate and adaptive immunity. enterovirus 71 (ev71) is one of primary pathogens that cause hand-foot-mouth disease. here, we identify rela(p65) as a novel binding partner for ev71 2c protein from yeast two-hybrid screen. by interaction with ipt domain of p65, 2c reduces the formation of heterodimer p65/p50, the predominant form of nf-κb. we also show that picornavirus 2c family proteins inhibit nf-κb activation an ...201526394554
quinolizidine alkaloids reduced mortality in ev71-infected mice by compensating for the levels of t cells.recent outbreak of hand, foot and mouse disease caused by enterovirus 71 is a serious threat to infants and children in asia-pacific countries. no vaccines or antiviral therapies are available against this infection. in this study, we found that quinolizidine alkaloids could improve the levels of t cells in mice. the structure-activity relationships demonstrated that the oxidation and double bonds are important for the excellent potency. oxysophocarpine, the most effective compound of six quinol ...201526189894
development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human enterovirus-71 vaccine encapsulated carrier.this study introduces a new approach for enhancing immunity toward mucosal vaccines. hev71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific iga & igg levels and viral neutralizing antibody titers. the antibody responses induced in rabbits by the different formulations delivered by a sing ...201526186664
immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates.a vaccine against human enterovirus 71 (ev-a71) is urgently needed to combat outbreaks of ev-a71 and in particular, the serious neurological complications that manifest during these outbreaks. in this study, an ev-a71 virus-like-particle (vlp) based on a b5 subgenogroup (ev-a71-b5 vlp) was generated using an insect cell/baculovirus platform. biochemical analysis demonstrated that the purified vlp had a highly native procapsid structure and initial studies in vivo demonstrated that the vlps were ...201526271825
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