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correction: routine pediatric enterovirus 71 vaccination in china: a cost-effectiveness analysis.[this corrects the article doi: 10.1371/journal.pmed.1001975.].201627050103
genetic evolution of human enterovirus a71 subgenotype c4 in shenzhen, china, 1998-2013.human enterovirus a71 (ev-a71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (hfmd) among children. this study identified the mutations of ev-a71 vp1 amino acid residues over a number of years and explored the possible association of identified mutations and hfmd epidemic outbreaks in shenzhen, china.201627038503
genomic and immunologic factors associated with viral pathogenesis in a lethal ev71 infected neonatal mouse model.hand, foot and mouth disease (hfmd) caused by enterovirus 71 (ev71) has emerged as a major health problem in china and worldwide. the present study aimed to understand the virological features of ev71 and host responses resulting from ev71 infection. six different ev71 strains were isolated from hfmd patients with severe or mild clinical symptoms, and were analyzed for pathogenicity in vitro and in vivo. the results demonstrated that the six virus strains exhibited similar cytopathogenic effects ...201627035332
pulmonary and central nervous system pathology in fatal cases of hand foot and mouth disease caused by enterovirus a71 infection.in the past 17 years, neurological disease associated with enterovirus a71 (ev-a71) has increased dramatically in the asia-pacific region with a high fatality rate in young infants, often due to pulmonary oedema, however the mechanism of this oedema remains obscure. we analysed the brainstem, heart and lungs of 15 fatal cases of confirmed ev-a71 infection in order to understand the pathophysiological mechanism of death and pulmonary oedema. in keeping with other case studies, the main cause of d ...201627020504
cyclical patterns of hand, foot and mouth disease caused by enterovirus a71 in malaysia.enterovirus a71 (ev-a71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (hfmd) in children. in malaysia, since the first ev-a71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2-3 years for reasons that remain unclear. we hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). neutralizing antibody titers against ev-a71 were measured in 2,141 residual serum samples coll ...201627010319
differential regulation of tlr signaling on the induction of antiviral interferons in human intestinal epithelial cells infected with enterovirus 71.enterovirus 71 (ev71) causes hand-foot-and-mouth disease, which can lead to fatal neurological complications in young children and infants. few gastrointestinal symptoms are observed clinically, suggesting the presence of a unique immunity to ev71 in the gut. we reported a robust induction of interferons (ifns) in human intestinal epithelial cells (ht-29), which was suppressed in other types such as rd and hela cells. the underlying mechanism for the apparent difference remains obscure. in this ...201627007979
gan-lu-siao-du-yin, a prescription of traditional chinese medicine, inhibited enterovirus 71 replication, translation, and virus-induced cell apoptosis.gan-lu-siao-du-yin (glsdy) is a prescription of traditional chinese medicine. glsdy contains 11 ingredients and is commonly used for endemic diseases. enterovirus 71 (ev71) is an endemic disease that can cause meningoencephalitis with mortality and neurologic sequelae without any effective management. it is unknown whether glsdy is effective against ev71 infection.201626993050
fragment-wise design of inhibitors to 3c proteinase from enterovirus 71.enterovirus 71 (ev71) is a causative agent of hand, foot and mouth disease (hfmd), which can spread its infection to central nervous and other systems with severe consequence. a key factor in the replication of ev71 is its 3c proteinase (3c(pro)), a significant drug target. peptidomimetics were employed as inhibitors of this enzyme for developing antivirals. however, the peptide bonds in these peptidomimetics are a source of low bioavailability due to their susceptibility to protease digestion. ...201626987809
enterovirus a71 genogroups c and e in children with acute flaccid paralysis, west africa. 201626982072
routine pediatric enterovirus 71 vaccination in china: a cost-effectiveness analysis.china accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (hfmd) cases reported to who during 2010-2014. enterovirus 71 (ev71) is responsible for most of the severe hfmd cases. three ev71 vaccines recently demonstrated good efficacy in children aged 6-71 mo. here we assessed the cost-effectiveness of routine pediatric ev71 vaccination in china.201626978565
bpifb6 regulates secretory pathway trafficking and enterovirus replication.bactericidal/permeability-increasing protein (bpi) fold-containing family b, member 3 (bpifb3) is an endoplasmic reticulum (er)-localized host factor that negatively regulates coxsackievirus b (cvb) replication through its control of the autophagic pathway. here, we show that another member of the bpifb family, bpifb6, functions as a positive regulator of cvb, and other enterovirus, replication by controlling secretory pathway trafficking and golgi complex morphology. we show that similar to bpi ...201626962226
[role of toll-like receptor 7 in the production of inflammatory cytokines in ev-a71-infected human jurkat t cells].to investigate the expression of toll-like receptor (tlr) mrna in enterovirus 71(ev-a71) infected human jurkat t cells and clarify the role of tlrs in the pathogenesis of ev-a71 infection-induced inflammation.201626957247
structural basis for recognition of human enterovirus 71 by a bivalent broadly neutralizing monoclonal antibody.enterovirus 71 (ev71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. we have recently identified a highly potent anti-ev71 neutralizing monoclonal antibody, termed d5. here we investigated the structural basis for recognition of ev71 by the antibody d5. four three-dimensional structures of ev71 particles in complex with igg or fab of d5 were reconstructed by cryo-electron microscopy (cryo-em) single parti ...201626938634
mri signal intensity differentiation of brainstem encephalitis induced by enterovirus 71: a classification approach for acute and convalescence stages.the objective of this study is to assess standardized histograms of signal intensities of t1 signal and t2 signal on sagittal view without enhancement during (1) acute stage, and (2) convalescence stage of pediatric patients with enterovirus 71 related brainstem encephalitis (be), and with respect to (3) healthy normal.201626917424
pilot surveillance for childhood encephalitis in australia using the paediatric active enhanced disease surveillance (paeds) network.we aimed to assess the performance of active surveillance for hospitalized childhood encephalitis in new south wales (nsw) using the paediatric active enhanced disease surveillance (paeds) network to inform methodology for the nationwide australian childhood encephalitis (ace) study. we piloted active surveillance for suspected encephalitis from may to december 2013 at the children's hospital at westmead, sydney, nsw. cases were ascertained using four screening methods: weekday nurse screening o ...201626916674
synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3c protease inhibitors.α-keto amide derivatives as enterovirus 71 (ev71) 3c protease (3c(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (sar) study indicated that small moieties were primarily tolerated at p1' and the introduction of para-fluoro benzyl at p2 notably improved the potency of inhibitor. inhibitors 8v, 8w and 8x exhibited satisfactory activity (ic50=1.32±0.26μm, 1.88±0.35μm and 1.52±0.31μm, respectively) and favorable cc50 ...201626916437
pyruvate carboxylase activates the rig-i-like receptor-mediated antiviral immune response by targeting the mavs signalosome.when retinoic acid-inducible gene 1 protein (rig-i)-like receptors sense viral dsrna in the cytosol, rig-i and melanoma differentiation-associated gene 5 (mda5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (mavs) and initiate antiviral immune responses. in this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (pc) plays an essential role in the virus-triggered activation of nuclear factor kappa b (nf-κb) signaling mediat ...201626906558
intravenous magnesium sulfate for the management of severe hand, foot, and mouth disease with autonomic nervous system dysregulation in vietnamese children: study protocol for a randomized controlled trial.over the last 15 years, hand, foot, and mouth disease (hfmd) has emerged as a major public health burden across the asia-pacific region. a small proportion of hfmd patients, typically those infected with enterovirus 71 (ev71), develop brainstem encephalitis with autonomic nervous system (ans) dysregulation and may progress rapidly to cardiopulmonary failure and death. although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a ...201626896318
ambulatory pediatric surveillance of hand, foot and mouth disease as signal of an outbreak of coxsackievirus a6 infections, france, 2014-2015.the clinical impact of enteroviruses associated with hand, foot and mouth disease (hfmd) is unknown outside asia, and the prevalence of enterovirus a71 (ev-a71) in particular might be underestimated. to investigate the prevalence of enterovirus serotypes and the clinical presentations associated with hfmd in france, we conducted prospective ambulatory clinic-based surveillance of children during april 2014-march 2015. throat or buccal swabs were collected from children with hfmd and tested for t ...201627767012
development and evaluation of a non-ribosomal random pcr and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens.hand, foot and mouth disease (hfmd) has become a major public health problem across the asia-pacific region, and is commonly caused by enterovirus a71 (ev-a71) and coxsackievirus a6 (cv-a6), cv-a10 and cv-a16. generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. the frequent replacements among ev serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping pcrs for whole-genome sequencing. we developed ...201627388326
synthesis of pyrazine-1,3-thiazine hybrid analogues as antiviral agent against hiv-1, influenza a (h1n1), enterovirus 71 (ev71), and coxsackievirus b3 (cvb3).a novel series of pyrazine-1,3-thiazine hybrid conjugates were synthesized in excellent yield. these derivatives were subsequently tested against human immunodeficiency virus (hiv-1); hemagglutinin type 1 and neuraminidase type 1-'influenza' a (h1n1) virus; enterovirus 71 (ev71); and coxsackievirus b3. the effect of these conjugates on the key enzymes responsible for the progression of these viral infections was also illustrated via enzyme-based assay, such as hiv-1 reverse transcriptase (rt) an ...201627062664
enteroviruses in the early 21st century: new manifestations and challenges.enteroviruses cause a wide variety of diseases with neurologic, respiratory, skin, and gastrointestinal findings. the purpose of this review is to clarify changes in the classification of enteroviruses, provide information about recent disease outbreaks, and to summarize progress toward the treatment and prevention of these infections.201626709690
isolation of an imported subgenotype b5 strain of human enterovirus a71 in chongqing city, china, 2014.enterovirus a71 (ev-a71) is the main pathogen responsible for large outbreaks of hand, foot, and mouth disease (hfmd) in mainland china, and the dominant ev-a71 strains belong to subgenotype c4. to date, only one imported subgenotype b5 of ev-a71 has been reported in xiamen city fujian province, 2009.201627357279
human sentinel surveillance of influenza and other respiratory viral pathogens in border areas of western cambodia.little is known about circulation of influenza and other respiratory viruses in remote populations along the thai-cambodia border in western cambodia. we screened 586 outpatients (median age 5, range 1-77) presenting with influenza-like-illness (ili) at 4 sentinel sites in western cambodia between may 2010 and december 2012. real-time reverse transcriptase (rrt) pcr for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral suscept ...201627028323
functional assessment and structural basis of antibody binding to human papillomavirus capsid.persistent high-risk human papillomavirus (hpv) infection is linked to cervical cancer. two prophylactic virus-like particle (vlp)-based vaccines have been marketed globally for nearly a decade. here, we review the hpv pseudovirion (psv)-based assays for the functional assessment of the hpv neutralizing antibodies and the structural basis for these clinically relevant epitopes. the psv-based neutralization assay was developed to evaluate the efficacy of neutralization antibodies in sera elicited ...201626676802
direct identification of enteroviruses in cerebrospinal fluid of patients with suspected meningitis by nested pcr amplification.enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. in the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. we developed rt-nested pcr amplification of the genomic region coding viral structural protein vp1 for direct identification ...201626751470
predominance of enterovirus b and echovirus 30 as cause of viral meningitis in a uk population.enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. with reports of unusually severe neurological disease in some patients infected with enterovirus d68 in north america, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this uk midlands population, a retrospective regional surveillance study was performed.201627367546
erratum to: antiviral activity of lactobacillus reuteri protectis against coxsackievirus a and enterovirus 71 infection in human skeletal muscle and colon cell lines. 201627855715
inhibition of enterovirus vp4 myristoylation is a potential antiviral strategy for hand, foot and mouth disease.the hand, foot and mouth disease (hfmd) can result from infections by a plethora of human enteroviruses of the species enterovirus a and b. these infections are highly contagious, resulting in regular outbreaks especially in the asia-pacific region in the recent decade. although this disease is generally a childhood affliction which manifests as a mild, febrile illness accompanied by the vesicles on the hands, feet and mouth, permanent morbidity or even fatality can result from severe forms of t ...201627520386
antiviral activity of lactobacillus reuteri protectis against coxsackievirus a and enterovirus 71 infection in human skeletal muscle and colon cell lines.recurrence of hand, foot and mouth disease (hfmd) pandemics continues to threaten public health. despite increasing awareness and efforts, effective vaccine and drug treatment have yet to be available. probiotics have gained recognition in the field of healthcare worldwide, and have been extensively prescribed to babies and young children to relieve gastrointestinal (gi) disturbances and diseases, associated or not with microbial infections. since the faecal-oral axis represents the major route ...201627341804
neurologic manifestations of enterovirus 71 infection in korea.enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. here, we aimed to describe the clinical features, magnetic resonance imaging (mri) findings, and cerebrospinal fluid (csf) profiles of patients presenting with neurologic complications of enterovirus 71 infection. we retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infectio ...201627051240
ev71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (hfmd).on december 3rd 2015, the china food and drug administration (cfda) approved the first inactivated enterovirus 71 (ev71) whole virus vaccine for preventing severe hand, foot and mouth disease (hfmd). as one of the few preventive vaccines for children's infectious diseases generated by the developing countries in recent years, ev71 vaccine is a blessing to children's health in china and worldwide. however, there are still a few challenges facing the worldwide use of ev71 vaccine, including the ap ...201626732723
paediatric active enhanced disease surveillance inaugural annual report, 2014.the paediatric active enhanced disease surveillance (paeds) network is a hospital-based active surveillance system employing prospective case ascertainment of selected uncommon vaccine preventable diseases and potential adverse events following immunisation (aefi). paeds enhances other australian surveillance systems by providing prospective detailed clinical and laboratory data for the same child.201628278415
evaluation of antiviral activity of zanthoxylum species against picornaviruses.human rhinoviruses and enteroviruses (family picornaviridae) infect millions of people worldwide each year, but little is known about effective therapeutical treatment for the infection caused by these viruses. we sought to determine whether or not zanthoxylum (rutaceae) species can exhibit antiviral activity against picornaviruses. the leaf parts of four zanthoxylum species were extracted with methanol, and the extracts were investigated for their antiviral activity against picornaviruses using ...201628053847
epidemiologic features of enterovirus 71-associated hand-foot-and-mouth disease from 2009 to 2013 in zhejiang, china.enterovirus 71 (ev71) usually causes hand-foot-and-mouth disease (hfmd) with severe clinical symptoms and even deaths in china. there is no efficient antiviral drug to protect against severe ev71-associated hfmd, making the development of ev71 vaccines therefore a priority. however, the potential target subject population(s) to be immunized with ev71 vaccine are not well understood. in this study, we characterized the epidemiology regarding ev71-associated hfmd on the basis of provincial-level s ...201628042848
changes of circulating th22 cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection.interleukin (il)-22+cd4+t (th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of th22 cells remains largely unclear in children with hand, foot, and mouth disease (hfmd) caused by enterovirus 71 (ev71). this study aims to explore the role of circulating il-22+il-17a-cd4+t (cth22) cells in children with ev71-associated hfmd. we found that during the acute stage of illness, the frequencies of cth22 and circulating il-22+il-17a+cd4+t ...201628030850
galectin-3 and its genetic variation rs4644 modulate enterovirus 71 infection.galectin-3, a chimeric type β-galactoside-binding protein, is known to modulate viral infection; however, its role in enterovirus 71 (ev71) infection has not been investigated. we generated galectin-3 null rhabdomyosarcoma (rd) cells and evaluated whether ev71 infection would be affected. in galectin-3 null cells, the released and intracellular ev71 viral loads were suppressed after 24 h of infection, and cell death rates were significantly lower, while cell proliferation remained unaltered. in ...201628002441
[surveillance on the epidemiological and etiological characteristics of hand-foot-mouth disease during the outbreaks in three cities of jiangsu province, 2012-2015].objective: to analyze the epidemiological and etiological characteristics through monitoring the outbreaks of hand-foot-mouth disease (hfmd), in three cities of jiangsu province from 2012 to 2015 and to provide evidence for prevention and control of the disease. methods: data related to cases of hfmd during the outbreaks was collected through active surveillance programs in three cities of jiangsu province, under the guidelines of clusters and outbreaks of hfmd (2012 edition hfmd). features rela ...201627998408
characterization of enterovirus 71 infection and associated outbreak of hand, foot, and mouth disease in shawo of china in 2012.infection of enterovirus 71 (ev71) and associated hand, foot, and mouth disease (hfmd) are recognized as emerging public health issues worldwide. hundreds of thousands of children are annually infected with ev71 and develop hfmd in china alone. studies of ev71 infection are critical to the treatment and prevention of the associated hfmd outbreaks. in this report, we studied an outbreak of 105 hfmd cases in shawo township of china between september to october 2012. more than 90% of cases were chi ...201627941929
comparative genomic analysis of enterovirus 71 revealed six new potential neurovirulence-associated sites.in the present study, the complete genomes of four common (4/ev71/wenzhou/chn/2014, 15/ ev71/wenzhou/chn/2014, 116/ev71/wenzhou/ chn/2014, and 120/ev71/wenzhou/chn/2014) and two virulent (11/ev71/wenzhou/chn/2014 and 109/ev71/wenzhou/chn/2014) enterovirus 71 (ev71) isolates were sequenced and described. they are 7405 bp in length and belong to ev71 sub-genotype c4 (c4a cluster). nucleotide sequence alignment revealed six nucleotide variations (gp151→tp151, gp199→ap199, gp261→tp261, ap328→cp328, ...201627927278
severe paediatric conditions linked with ev-a71 and ev-d68, france, may to october 2016.we report 59 cases of severe paediatric conditions linked with enterovirus (ev)-a71 and ev-d68 in france between may and october 2016. fifty-two children had severe neurological symptoms. ev sequence-based typing for 42 cases revealed ev-a71 in 21 (18 subgenotype c1, detected for the first time in france) and ev-d68 in eight. clinicians should be encouraged to obtain stool and respiratory specimens from patients presenting with severe neurological disorders for ev detection and characterisation.201627918268
motor coordination and balance measurements reveal differential pathogenicity of currently spreading enterovirus 71 strains in human scarb2 transgenic mice.enterovirus 71 (ev71) has caused large-scale epidemics with neurological complications in the asia-pacific region. the c4a and b5 strains are the two major genotypes circulating in many countries recently. this study used a new protocol, a motor coordination task, to assess the differential pathogenicity of c4a and b5 strains in human scarb2 transgenic mice. we found that the pathogenicity of c4a viruses was more severe than that of b5 viruses. moreover, we discovered that an increased level of ...201627902385
hand, foot, and mouth disease in hunan province, china, 2009-2014: epidemiology and death risk factors.hand, foot, and mouth disease (hfmd) is an arising public health problem in asia, including china. epidemiological data is necessary to enable judicious public health responses and interventions. we analyzed the epidemiological and laboratory data of 759,301 hfmd cases reported to the hunan provincial center for disease control and prevention from 1 january 2009 to 31 december 2014. univariate and multivariable conditional logistic regression analyses were used to identify risk factors of fatali ...201627898715
identification of molecular determinants of cell culture growth characteristics of enterovirus 71.hand, foot and mouth disease is caused by enterovirus 71 (ev-a71) and coxsackieviruses. ev-a71 infection is associated with high fever, rashes and ulcers but more severe symptoms such as cardiopulmonary failure and death have been reported. the lack of vaccines highlighted the urgency of developing preventive agents against ev-a71. the molecular determinants of virulent phenotypes of ev-a71 is unclear. it remains to be investigated if specific molecular determinants would affect the cell culture ...201627894305
inhibitory effects of bee venom and its components against viruses in vitro and in vivo.bee venom (bv) from honey bee (apis melifera l.) contains at least 18 pharmacologically active components including melittin (mlt), phospholipase a2 (pla2), and apamin etc. bv is safe for human treatments dose dependently and proven to possess different healing properties including antibacterial and antiparasitidal properties. nevertheless, antiviral properties of bv have not well investigated. hence, we identified the potential antiviral properties of bv and its component against a broad panel ...201627888461
sirt1 inhibits ev71 genome replication and rna translation by interfering with the viral polymerase and 5'utr rna.enterovirus 71 (ev71) possesses a single-stranded positive rna genome that contains a single open reading frame (orf) flanked by a 5' untranslated region (5'utr) and a polyadenylated 3'utr. here, we demonstrated that ev71 activates the production of silent mating type information regulation 2 homolog 1 (sirt1), a histone deacetylase (hdac). ev71 further stimulates sirt1 sumoylation and deacetylase activity, and enhances sirt1 translocation from the nucleus to the cytoplasm. more interestingly, a ...201627875274
enterovirus 71 infection of motor neuron-like nsc-34 cells undergoes a non-lytic exit pathway.enterovirus 71 (ev71) causing hand, foot and mouth disease, is regarded as the most important neurotropic virus worldwide. ev71 is believed to replicate in muscles and infect motor neurons to reach the central nervous system (cns). to further investigate the mechanisms involved, we have employed the motor neuron cell line nsc-34. nsc-34 cells were permissive to ev71 and virus production yields were strain-dependent with differential efficacy at the entry, replication and egress steps. furthermor ...201627849036
enterovirus-71 genotype c isolated in peru between 2006 and 2009.enterovirus-71 (ev71) was first isolated in california, united states in 1969, belongs to the genus enterovirus, family picornaviridae. although infection normally causes mild, often undiagnosed illness, it can cause central nervous system infections that could turn fatal. based on vp1 gene analysis, ev71 has been classified into six separate genotypes. although the molecular epidemiology of ev71 has been well described via studies originating from asia and europe, it is mostly unknown in south ...201627833060
enterovirus 71 infection and neurological complications.since the outbreak of the enterovirus 71 (ev71) infection in malaysia in 1997, large epidemics of ev71 have occurred in the asia-pacific region. many children and infants have died from serious neurological complications during these epidemics, and ev71 infection has become a serious public health problem in these areas. ev71 infection causes hand, foot and mouth disease (hfmd) in children, and usually resolves spontaneously. however, ev71 occasionally involves the central nervous system (cns), ...201627826325
children's caregivers and public playgrounds: potential reservoirs of infection of hand-foot-and-mouth disease.hand-foot-and-mouth disease (hfmd) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in china. this study aimed to exploring the effects on hfmd transmission of children's caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. total children's 257 samples (98 children's caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71 ...201627819276
epidemiological characteristics and influential factors of hand, foot and mouth disease (hfmd) reinfection in children in anhui province.hand, foot and mouth disease (hfmd) is an acute contagious condition caused by a spectrum of human enteroviruses. hfmd reinfection is common in the absence of cross-protection from other virus subtypes. this study focused on reinfection in children in anhui province, china between 2008 and 2013 using surveillance system data. we classified 8960 cases as reinfected, corresponding to a rate of 2·02%. the reinfection rate was higher in boys than in girls [odds ratio (or) 1·27, 95% confidence interv ...201626027435
peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3c protease: a p2-p4 study.enterovirus 71 (ev71) is a highly infectious pathogen primarily responsible for hand, foot, and mouth disease, particularly among children. currently, no approved antiviral drug has been developed against this disease. the ev71 3c protease is deemed an attractive drug target due to its crucial role in viral polyprotein processing. rupintrivir, a peptide-based inhibitor originally developed to target the human rhinovirus 3c protease, was found to inhibit the ev71 3c protease. in this communicatio ...201625792507
a comprehensive procedure for antiviral inhibitor discovery using ev71 as an example.the prevalence of chronic viral infectious diseases, the emergence and re-emergence of new viral infections, and in particular, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. in this work, we introduce a comprehensive system using enteroviruses ...201726942222
ocular pathology: role of emerging viruses in the asia-pacific region-a review.the role of viral infections in ocular pathology varies greatly, involving all the components of the eye. some viruses like herpes simplex, herpes zoster, adenovirus, enterovirus 70, influenza virus, human immunodeficiency virus, and cytomegalovirus are well-known for their role in ocular pathology. in recent years, emerging and resurging viral infections represent an important public health problem. the asia-pacific region has witnessed a number of pandemic and epidemic outbreaks caused by thes ...201726107917
predicting severe enterovirus 71 infection: age, comorbidity, and parental behavior matter.enterovirus 71 (ev71) is one of the major pathogens that cause severe enteroviral infections. our aim was to study the behavioral and household risk factors for its serious complications.201725678038
dynamic interaction of enterovirus 71 and dendritic cells in infected neonatal rhesus macaques.enterovirus 71 (ev71) is one of the main pathogens responsible for hand, foot, and mouth disease (hfmd). infection with ev71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. based on the previous pathological study of ev71 infections in neonatal rhesus macaques, our work using this animal model and an ev71 chimera that expresses enhanced green fluorescent protein (egfp-ev71) primarily explored where ev71 localizes and prolif ...201728540257
a novel combined vaccine based on monochimeric vlp co-displaying multiple conserved epitopes against enterovirus 71 and varicella-zoster virus.chicken pox and hand, foot and mouth disease (hfmd) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. varicella-zoster virus (vzv) and enterovirus 71 (ev71), respectively, are the principal epidemic pathogens causing these two diseases. to investigate the possibility of developing a novel combined vaccine to prevent chicken pox and hfmd, we constructed three chimeric virus-like particles (vlps) (termed hbc-v/1/2, hbc-2/v/1 and hbc- ...201728408118
pulmonary edema following central nervous system lesions induced by a non- mouse-adapted ev71 strain in neonatal balb/c mice.enterovirus (ev) infection has been a serious health issue in asia-pacific region. it has been indicated that the occurrence of fatal hand foot and mouth disease (hfmd) cases following ev71 infection is mainly attributed to pulmonary edema. however, the development of pulmonary disorders after ev71 infection remains largely unknown. to establish an ev71-infected animal model and further explore the underlying association of central nervous system (cns) invasion with pulmonary edema, we isolated ...201729282065
n-terminal pro-b-type natriuretic peptide for the prognostic prediction of severe enterovirus 71-associated hand, foot, and mouth disease.the aim of this study was to determine whether n-terminal pro-b-type natriuretic peptide (nt-probnp) can predict impending brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, cardiopulmonary failure, and death in children with severe enterovirus 71 (ev71)-associated hand, foot, and mouth disease (hfmd).201727818360
glucocorticoids prevent enterovirus 71 capsid protein vp1 induced calreticulin surface exposure by alleviating neuronal er stress.severe hand-foot-and-mouth disease (hfmd) caused by enterovirus 71 (ev71) always accompanies with inflammation and neuronal damage in the central nervous system (cns). during neuronal injuries, cell surface-exposed calreticulin (ecto-crt) is an important mediator for primary phagocytosis of viable neurons by microglia. our data confirmed that brainstem neurons underwent neuronophagia by glia in ev71-induced death cases of hfmd. ev71 capsid proteins vp1, vp2, vp3, or vp4 did not induce apoptosis ...201727848175
enterovirus 71 3c promotes apoptosis through cleavage of pinx1, a telomere binding protein.enterovirus 71 (ev71) is an emerging pathogen causing hand, foot, and mouth disease (hfmd) and fatal neurological diseases in infants and young children due to their underdeveloped immunocompetence. ev71 infection can induce cellular apoptosis through a variety of pathways, which promotes ev71 release. the viral protease 3c plays an important role in ev71-induced apoptosis. however, the molecular mechanism responsible for 3c-triggered apoptosis remains elusive. here, we found that ev71 3c direct ...201727847364
rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.human enterovirus 71 (ev71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (hfmd) in asia. currently, there are no drugs available for the prevention and treatment of hfmd. in this study, we compared the anti-ev71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from chinese herbs chinese rhubarb, artemisia carvifolia and astragalus, respectively, which have been traditionally used for the treatment and ...201727840410
development of a fluorescence resonance energy transfer-based intracellular assay to identify novel enterovirus 71 antivirals.enterovirus 71 (ev71) is considered one of the most virulent pathogens in the family picornaviridae. however, there have been no effective treatments for the severe complications caused by ev71. development of new drugs against targets that are essential for viral replication often requires screening large collections of compounds, for which a high-throughput screening platform is needed. in this study, a drug-screening platform was developed based on a genetically engineered cell line that disp ...201727873071
immunoreactivity analysis of the nonstructural proteins of human enterovirus 71.human enterovirus 71 (ev-a71) is one of the main etiological agents of hand, foot, and mouth disease (hfmd), which has been prevalent mainly in the asia-pacific region in the past several decades. the nonstructural proteins of ev-a71 will be expressed significantly during viral replication in host cells after ev-a71 infection. for the determination of the antibodies response against nonstructural proteins of ev-a71, in this study, the complete 2abc, 3abc, and 3d proteins were expressed in escher ...201727870604
clinically isolated enterovirus a71 subgenogroup c4 strain with lethal pathogenicity in 14-day-old mice and the application as an ev-a71 mouse infection model.the enterovirus a71 (ev-a71) subgenogroup c4 is prevalent in china. ev-a71 causes hand, foot and mouth disease (hfmd) in children and may lead to severe neurological diseases. the development of antiviral and protective vaccines against ev-a71 is significantly hindered by the lack of suitable animal models to recapitulate human neurological symptoms. in this study, gz-cii, a highly virulent ev-a71 subgenogroup c4 strain, was isolated from hospitalized children with hfmd. intraperitoneal infectio ...201727864074
vp1 residues around the five-fold axis of enterovirus a71 mediate heparan sulfate interaction.enterovirus a71 (ev-a71) is a neurotropic enterovirus that uses heparan sulfate as an attachment receptor. the molecular determinants of ev-a71-heparan sulfate interaction are unknown. with in silico heparin docking and mutagenesis of all possible lysine residues in vp1, we identified that k162, k242 and k244 are responsible for heparin interaction and inhibition. ev-a71 mutants with k242a and k244a rapidly acquired compensatory mutations, t100k or e98a, and q145r-t237n respectively, which resto ...201727875780
an elaborate landscape of the human antibody repertoire against enterovirus 71 infection is revealed by phage display screening and deep sequencing.enterovirus 71 (ev71) causes outbreaks of hand, foot and mouth disease (hfmd), primarily in the asia-pacific area, that are often associated with complications of severe to fatal neurological symptoms. there are currently no anti-viral therapies or vaccines available for the treatment of ev71 infection. illustrating human antibody responses neutralizing ev71 infection could potentially provide valuable information for the development of effective therapies and vaccines. here, we constructed a co ...201727929745
structure-activity relationship studies on a trp dendrimer with dual activities against hiv and enterovirus a71. modifications on the amino acid.we have recently described a new class of dendrimers with tryptophan (trp) on the surface that show dual antiviral activities against hiv and ev71 enterovirus. the prototype compound of this family is a pentaerythritol derivative with 12 trps on the periphery. here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. with this aim, novel dendrimers containing different amino acids (aromatic and non-a ...201728017762
lithium chloride inhibits early stages of foot-and-mouth disease virus (fmdv) replication in vitro.foot-and-mouth disease virus (fmdv) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. fmd vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. however, the use of fmd vaccines to protect early infection is limited. therefore, the alternative strategy of applying antiviral agents is required to control the spread of fmdv in outbreak situations. as previously reported, licl ha ...201728390158
epidemics and aetiology of hand, foot and mouth disease in xiamen, china, from 2008 to 2015.over the past 8 years, human enteroviruses (hevs) have caused 27 227 cases of hand, foot and mouth disease (hfmd) in xiamen, including 99 severe cases and six deaths. we aimed to explore the molecular epidemiology of hfmd in xiamen to inform the development of diagnostic assays, vaccines and other interventions. from january 2009 to september 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription pcr that targeted the hev 5' untranslated region and viral protei ...201728367766
outbreak of brainstem encephalitis associated with enterovirus-a71 in catalonia, spain (2016): a clinical observational study in a children's reference centre in catalonia.to describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (ev) infection in catalonia (spain), a setting where these manifestations were uncommon.201728344164
enterovirus 71 neutralizing antibodies seroepidemiological research among children in guangzhou, china between 2014 and 2015: a cross-sectional study.a hand-foot-mouth disease outbreak occurred in 2014 around guangdong. the purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. serum specimens were collected from children in communities from january 2014 to march 2015 in guangzhou. a total of 197 serum s ...201728335535
efficacy and safety evaluation of a chlorine dioxide solution.in this study, a chlorine dioxide solution (uc-1) composed of chlorine dioxide was produced using an electrolytic method and subsequently purified using a membrane. uc-1 was determined to contain 2000 ppm of gaseous chlorine dioxide in water. the efficacy and safety of uc-1 were evaluated. the antimicrobial activity was more than 98.2% reduction when uc-1 concentrations were 5 and 20 ppm for bacteria and fungi, respectively. the half maximal inhibitory concentrations (ic50) of h1n1, influenza vi ...201728327506
squamous epitheliotropism of enterovirus a71 in human epidermis and oral mucosa.hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by enterovirus a71 (genus: enterovirus, family: picornaviridae). typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of enterovirus a71 in human skin and oral mucosa are unknown. in enterovirus a71-infect ...201728322333
the golgi protein acbd3 facilitates enterovirus 71 replication by interacting with 3a.enterovirus 71 (ev71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. although ev71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. by screening human cdna library, we uncover that the golgi resident protein acyl-coenzyme a binding domain-containing 3 (acbd3) serves as a target of the 3a protein of ev71. this interaction occurs in cells expressing 3a or i ...201728303920
best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review.hand, foot, and mouth disease continues to cause seasonal epidemics in the asia-pacific region. since the current enterovirus 71 vaccines do not provide cross-protection for all enterovirus species that cause hand, foot, and mouth disease, there is an urgent need to identify appropriate detection tools and best practice to prevent its transmission and to effectively control its outbreaks. this systematic review aimed to identify characteristics of outbreak and assess the impact and effectiveness ...201728302925
a novel benzo-heterocyclic amine derivative n30 inhibits influenza virus replication by depression of inosine-5'-monophospate dehydrogenase activity.influenza virus is still a huge threat to the world-wide public health. host inosine-5'- monophosphate dehydrogenase (impdh) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative n30, which was designed to inhibit impdh.201728298229
the uncoupling of catalysis and translocation in the viral rna-dependent rna polymerase.the nucleotide addition cycle of nucleic acid polymerases includes two major events: the pre-chemistry active site closure leading to the addition of one nucleotide to the product chain; the post-chemistry translocation step moving the polymerase active site one position downstream on its template. in viral rna-dependent rna polymerases (rdrps), structural and biochemical evidences suggest that these two events are not tightly coupled, unlike the situation observed in a-family polymerases such a ...201728277928
enhancing enterovirus a71 vaccine production yield by microcarrier profusion bioreactor culture.hand, foot and mouth diseases (hfmd) are mainly caused by enterovirus a71 (ev-a71) infections. clinical trials in asia conducted with formalin-inactivated ev-a71 vaccine candidates produced from serum-free vero cell culture using either roller bottle or cell factory technology, are found to be safe and highly efficacious. to increase vaccine yields and reduce the production costs, the bioprocess improvement for ev-a71 vaccine manufacturing is currently being investigated. the parameters that cou ...201728274636
report from the world health organization's third product development for vaccines advisory committee (pdvac) meeting, geneva, 8-10th june 2016.the third meeting of who's product development for vaccines advisory committee (pdvac) was held in june 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase iii trials of a ...201728262332
correction: enterovirus 71 protease 2apro targets mavs to inhibit anti-viral type i interferon responses.[this corrects the article doi: 10.1371/journal.ppat.1003231.].201728253362
microrna screening identifies mir-134 as a regulator of poliovirus and enterovirus 71 infection.micrornas (mirnas) regulate virus replication through multiple mechanisms. poliovirus causes a highly debilitating disease and though global efforts to eradicate polio have sharply decreased polio incidence, unfortunately three countries (afghanistan, nigeria and pakistan) remain polio-endemic. we hypothesize that understanding the host factors involved in polio replication will identify novel prophylactic and therapeutic targets against polio and related viruses. in this data set, employing gen ...201728248924
recombinant heat shock protein 78 enhances enterovirus 71 propagation in vero cells and is induced in sk-n-sh cells during the infection.enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease (hfmd), which mainly occurs in children. children with ev71 infection can develop severe neurological diseases. heat shock protein 78 (hsp78) facilitates proper protein folding during viral propagation and is induced during virus infection. nevertheless, the role that hsp78 plays during ev71 infection is still unclear. in this study, recombinant hsp78 protein was expressed in a prokaryotic expression syste ...201728236071
flos farfarae inhibits enterovirus 71-induced cell injury by preventing viral replication and structural protein expression.enterovirus 71 (ev71) infection can cause airway symptoms, brainstem encephalitis, neurogenic shock, and neurogenic pulmonary edema with high morbidity and mortality. there is no proven therapeutic modality. flos farfarae is the dried flower bud of tussilago farfara l. that has been used to manage airway illnesses for thousands of years. it has neuro-protective activity and has been used to manage neuro-inflammatory diseases. however, it is unknown whether flos farfarae has activity against ev71 ...201728231741
human enterovirus 68 interferes with the host cell cycle to facilitate viral production.enterovirus d68 (ev-d68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the united states and other countries. little is known about the relationship between ev-d68 virus and host cells. in this study, we assessed the effect of the host cell cycle on ev-d68 viral production, as well as the ability of ev-d68 to manipulate host cell cycle progression. the results suggest that synchronization in g0/g1 phase, but not s phase, promotes viral production, ...201728229049
human enterovirus 71 protein interaction network prompts antiviral drug repositioning.as a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (ev71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, ev71-host protein interactions have not ...201728220872
a novel enterovirus 71 (ev71) virulence determinant: the 69th residue of 3c protease modulates pathogenicity.human enterovirus type 71 (ev71), the major causative agent of hand-foot-and-mouth disease, has been known to cause fatal neurological complications. unfortunately, the reason for neurological complications that have been seen in fatal cases of the disease and the relationship between ev71 virulence and viral genetic sequences remains largely undefined. the 3c protease (3c(pro)) of ev71 plays an irreplaceable role in segmenting the precursor polyprotein during viral replication, and intervening ...201728217559
[analysis of the clinical features of infections caused by enterovirus a71 (ev-a71) in balearic islands]. 201728215717
rapid detection and quantification of enterovirus 71 by a portable surface plasmon resonance biosensor.this study presents the first report on a label-free detection and rapid quantification method for human enterovirus 71 (ev71) using a portable surface plasmon resonance (spr) system. the spr sensor instrument was configured to run on low power in a miniaturized platform to improve the device portability for a wider application both in laboratories and in the field. a color tunable organic light emitting diode in red spectrum was attached on a trapezoidal prism for the disposable light source mo ...201728214745
clinical manifestations of severe enterovirus 71 infection and early assessment in a southern china population.enterovirus 71 (ev-a71) shows a potential of rapid death, but the natural history of the infection is poorly known. this study aimed to examine the natural history of ev-a71 infection.201728212620
association of toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in chinese children.enterovirus 71 (ev71) infection has become one of the major threats to children globally in recent years. toll-like receptor 3 (tlr3) plays an essential role in host defense against ev71 infection. this study was designed to assess the possible association between the tlr3c.1377c/t polymorphism and disease severity in chinese children with ev71 infection. the tlr3c.1377c/t gene polymorphism was identified in ev71-infected patients (n = 177), including mild cases (n = 99) and severe cases (n = 78 ...201728190199
the impact of hand, foot and mouth disease control policies in singapore: a qualitative analysis of public perceptions.hand foot and mouth disease (hfmd) is a widespread pediatric disease in asia. most cases are relatively mild and caused by coxsackie viruses, but in epidemics caused by enterovirus 71, severe complications can occur. in response to the deaths of dozens of children in a 1997 outbreak (podin in bmc public health 6:180,1 abubakar in virus res 61(1):1-9,2 who in3), singapore practices childcare centre surveillance, case-isolation, and short-term closure of centres. we conducted 44 in-depth interview ...201728179628
an ultrasensitive biosensing platform employing acetylcholinesterase and gold nanoparticles.enzyme-linked immunosorbent assay (elisa) is a well-known strategy for biomarker detection with a color change, which can be seen by the naked eyes. however, the moderate sensitivity of conventional elisa limits its applications in many cases where the concentrations of biomarker are very low, such as cancer diagnosis. here we describe an ultrasensitive colorimetric assay based on acetylcholinesterase (ache)-catalyzed hydrolysis reaction, whose products trigger the aggregation of gold nanopartic ...201728150210
interferon-α and inosine pranobex-mediated inhibition of reploication of human rna viruses in vitro.interferon- a (ifn-a), produced by immune cells, exhibits pleiotropic anti- viral activity. inosine pranobex (pi), a synthetic derivative of a purine, shows direct anti- viral activity, and also acts indirectly, by activation of immune cells. the aim of this study was to evaluate an in vitro inhibition of coxackievirus a16 (cai6), enterovirus 71 (ev71) and human parainfluenza virus 4 (hpiv-4) replication by pi in combination with ifn-a.201728146624
antiviral activity of acid beta-glucosidase 1 on enterovirus 71, a causative agent of hand-foot-mouth disease.enterovirus 71 (ev71) is a causative agent of hand-foot-mouth disease (hfmd). ev71 causes fever, rash, diarrhea, and, in some cases, acute encephalopathy/encephalitis, which can be fatal. no specific treatment is currently available for ev71 infection. here, we conducted a cdna library screen and identified acid β-glucosidase 1 (gba1; also known as β-glucocerebrosidase) as an ev71 resistance factor. the anti-ev71 function of gba1 was verified by gene transduction and knockdown experiments. cerez ...201728141506
hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells.human enterovirus 71 (ev71) causes severe hand, foot and mouse disease, accompanied by neurological complications. during the interaction between ev71 and the host, the virus subverts host cell machinery for its own replication. however, the roles of micrornas (mirnas) in this process remain obscure.201728101327
[association of tlr3-1377c/t gene polymorphisms and expression with susceptibility to enterovirus 71 encephalitis in children].to investigate the association of gene polymorphisms of toll-like receptor 3 (tlr3)-1377c/t and expression of tlr3 with the susceptibility to enterovirus 71 (ev71) encephalitis in children.201728100320
berberine inhibits enterovirus 71 replication by downregulating the mek/erk signaling pathway and autophagy.the mek-erk signaling pathway and autophagy play an important role for enterovirus71(ev71) replication. inhibition of mek-erk signaling pathway and autophagy is shown to impair ev71 replication. berberine (bbr), an isoquinoline alkaloid isolated from berberis vulgaris l., has been reported to have ability to regulate this signaling pathway and autophagy. herein, we want to determine whether berberine can inhibit ev71 infection by downregulating the mek/erk signaling pathway and autophagy.201728081706
2-year efficacy, immunogenicity, and safety of vigoo enterovirus 71 vaccine in healthy chinese children: a randomized open-label study.this study evaluated the 2-year efficacy, immunogenicity, and safety of the vigoo enterovirus 71 (ev71) vaccine.201728077584
enterovirus 71 induces apoptosis by directly modulating the conformational activation of pro-apoptotic protein bax.enterovirus 71 (eva71), a virus of the genus enterovirus in the family picornaviridae, is one of the main causative agents of hand, foot and mouth disease in infected infants and young children. in this study, we report that cells with eva71 infection exhibit increased levels of cytochrome c release and caspase-3 activation. eva71 infection induces the conformational activation of pro-apoptotic protein bax and the subsequent formation of oligomers of bax in mitochondria. inhibitors that block ca ...201728073399
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