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alumina-encapsulated vaccine formulation with improved thermostability and immunogenicity.developing vaccine formulations with excellent thermostability and immunogenicity remains a great challenge. by in situ encapsulating a live-attenuated strain of human enterovirus 71 (ev71) in alumina, we obtained a robust vaccine formulation named ev71@nanoalum, which features significantly enhanced thermostability and immunogenicity. this attempt follows a material-based tactic for vaccine improvement.201627098047
in vitro and in vivo studies of a potent capsid-binding inhibitor of enterovirus 71.enterovirus 71 (ev-a71) is an important pathogen that can cause severe neurological symptoms and even death. our aim was to identify potent anti-ev-a71 compounds and study their underlying mechanisms and in vivo activity.201627098012
direct detection and identification of enteroviruses from faeces of healthy nigerian children using a cell-culture independent rt-seminested pcr assay.recently, a cell-culture independent protocol for detection of enteroviruses from clinical specimen was recommended by the who for surveillance alongside the previously established protocols. here, we investigated whether this new protocol will show the same enterovirus diversity landscape as the established cell-culture dependent protocols. faecal samples were collected from sixty apparently healthy children in ibadan, nigeria. samples were resuspended in phosphate buffered saline, rna was extr ...201627087810
[etiology study on severe cases caused by hand-foot-mouth disease in children from henan province, 2014].to investigate the etiology of severe hand-foot-mouth disease (hfmd) in children in henan province.201627087228
[molecular epidemiology of hand-foot-mouth disease associated pathogen coxsackievirus a10 identified in fujian province, 2011-2014].to study the molecular epidemiology of hand-foot-mounth disease (hfmd) associated coxsackievirus a10 (cox a10) identified in fujian province.201627087227
structural characterization and antiviral activity of a novel heteropolysaccharide isolated from grifola frondosa against enterovirus 71.a novel heteropolysaccharide from grifola frondosa mycelia was extracted and purified using deae sephadex a-50 and sephadex g-200 chromatography. fourier transform infrared (ft-ir) spectroscopy and nuclear magnetic resonance ((1)h nmr and (13)c nmr) spectroscopy were used to decipher the structure of the purified g. frondosa polysaccharide (gfp1). chemical and spectral analysis revealed that gfp1, with an average molecular weight of 40.5kda, possessed a 1,6-β-d-glucan backbone with a single 1,3- ...201627083830
pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.it has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. this study demonstrated that administration of heat-killed enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. the influenza-mediated morbidity and lung inflammation in e. faecalis-treated mice decreased significantly compared with those of the control mice. furthermore, we found that the protection is associated wit ...201727072606
establishment of an animal challenge model as a potency assay for an inactivated enterovirus type 71 vaccine.enterovirus 71 (ev71) belongs to the enterovirus genus of the picornaviridae family, and its occurrence in asia is associated with hand-foot-and-mouth disease (hfmd), leading to death in some cases, in young children. an effective ev71 vaccine is therefore urgently needed. in this study, we established a two-step ev71 vaccine potency model. intraperitoneal injections in 2-day-old suckling mice were used to establish the ld50 of ev71 b4, b5, c2, c4, and c5 subgenotypes. only c4 caused hind limb p ...201627068365
characterization of coxsackievirus a6- and enterovirus 71-associated hand foot and mouth disease in beijing, china, from 2013 to 2015.etiology surveillance of hand foot and mouth disease (hfmd) in beijing showed that coxsackievirus a6 (cva6) became the major pathogen of hfmd in 2013 and 2015. in order to understand the epidemiological characteristics and clinical manifestations of cva6-associated hfmd, a comparison study among cva6-, ev71- (enterovirus 71), and cva16- (coxsackievirus a16) associated hfmd was performed.201627065963
milrinone in enterovirus 71 brain stem encephalitis.enterovirus 71 (ev71) was implicated in a widespread outbreak of hand-foot-and-mouth disease (hfmd) across the asia pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. neurogenic shock with pulmonary edema (pe) is a fatal complication of ev71 infection. among inotropic agents, milrinone is selected as a therapeutic agent for ev71- induced pe due to its immunopathogenesis. milrinone is a type iii phosphodiesterase inhibitor that has both inotr ...201627065870
susceptibilities of enterovirus d68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.compounds were evaluated for antiviral activity in rhabdomyosarcoma (rd) cells against a recent 2014 clinical isolate of enterovirus d68 (ev-d68), a 1962 strain of ev-68d, rhinovirus 87 (rv-87, serologically the same as ev-d68), and enterovirus 71 (ev-71). test substances included known-active antipicornavirus agents (enviroxime, guanidine hcl, pirodavir, pleconaril, and rupintrivir), nucleobase/nucleoside analogs (3-deazaguanine and ribavirin), and three novel epidithiodiketopiperazines (kcn-2, ...201627063860
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
the nuclear protein sam68 is recruited to the cytoplasmic stress granules during enterovirus 71 infection.our previous study found that the nuclear protein, 68-kda src-associated in mitosis protein (sam68), is translocated to the cytoplasm and forms punctate pattern during enterovirus 71 (ev71) infection [virus research, 180 (2014), 1-11]. however, the exact function of this punctate pattern in cytoplasm during ev71 infection remains unknown. in this study, we firstly have examined this punctate pattern of sam68 re-localization in the cytoplasm, and observed the obvious recruitments of sam68 to the ...201627057671
elevated expression of circulating mir876-5p is a specific response to severe ev71 infections.human enterovirus 71 (ev71) is a major causative agent of hand, foot, and, mouth disease, accounting for more than 65% of recent outbreaks. following enteroviral infection, the host responses are crucial indicators for the development of a diagnosis regarding the clinical severity of ev71 infections. in this study, we implemented nanostring ncounter technology to characterize the responses of serum microrna (mirna) profiles to various ev71 infection diseases. upon ev71 infection, 44 mirnas were ...201627052555
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
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
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
serum cholinesterase: a potential assistant biomarker for hand, foot, and mouth disease caused by enterovirus 71 infection.hand, foot, and mouth disease (hfmd) caused by enterovirus 71 (ev71) is a potentially life-threatening infectious disease that commonly occurs in children. diagnosis of hfmd caused by ev71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from hfmd. serum cholinesterase (sche) activity has frequently been reported as a potential biomarker for solid central nervous system tumors, chronic heart failure, and liver cirrhosis. however, its ...201627025584
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
meteorological factors affect the hand, foot, and mouth disease epidemic in qingdao, china, 2007-2014.hand, foot, and mouth disease (hfmd) has caused public health concerns worldwide. we aimed to investigate the effect of meteorological factors on the hfmd epidemic in qingdao, a port city in china. a total of 78641 cases were reported in qingdao between january 2007 and december 2014. of those, 71084 (90·39%) occurred in children aged 0-5 years, with an incidence of 1691·2/100000. the incidence increased from early spring, peaked between spring and summer, and decreased in late summer. aetiologi ...201627018924
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
enterovirus 71 induces dsrna/pkr-dependent cytoplasmic redistribution of grp78/bip to promote viral replication.grp78/bip is an endoplasmic reticulum (er) chaperone protein with the important function of maintaining er homeostasis, and the overexpression of grp78/bip alleviates er stress. our previous studies showed that infection with enterovirus 71 (ev71), a (+)rna picornavirus, induced grp78/bip upregulation; however, ectopic grp78/bip overexpression in er downregulates virus replication and viral particle formation. the fact that a virus infection increases grp78/bip expression, which is unfavorable f ...201627004760
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
status of research and development of vaccines for enterovirus 71.although outbreaks of hand, foot, and mouth disease (hfmd) in young children have long been recognized worldwide, the occurrence of rare and life-threatening neurological, respiratory, and cardiac complications has propelled this common condition into the spotlight as a major public health problem in the affected countries. various enteroviruses cause hfmd, but the severe complications have been mostly associated with enterovirus 71 (ev71). medical treatment is supportive and measures to interru ...201626973065
development and evaluation of a real-time method for testing human enteroviruses and coxsackievirus a16.hand, foot, and mouth disease (hfmd) is a common infectious disease caused by a group of the human enteroviruses (hev), including coxsackievirus a16 (ca16) and enterovirus 71 (ev71). in recent years, another hev-a serotype, ca6 or ca10, has emerged to be one of the major etiologic agents that can induce hfmd worldwide. the objective of this study is to develop specific, sensitive, and rapid methods to help diagnose hev and ca16 specifically by using simultaneous amplification testing (sat) based ...201626971632
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
2c proteins of enteroviruses suppress ikkβ phosphorylation by recruiting protein phosphatase 1.the nf-κb signaling network, which is an ancient signaling pathway, plays a pivotal role in innate immunity and constitutes a first line of defense against invading pathogens, including viruses. however, numerous viruses possess evolved strategies to antagonize the activation of the nf-κb signaling pathway. our previous study demonstrated that the nonstructural protein 2c of enterovirus 71 (ev71), which is the major pathogen of hand, foot, and mouth disease, inhibits tumor necrosis factor alpha ...201626962213
[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
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
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
serological detection and analysis of anti-vp1 responses against various enteroviruses (ev) (ev-a, ev-b and ev-c) in chinese individuals.the overall serological prevalence of ev infections based on elisa remains unknown. in the present study, the antibody responses against vp1 of the ev-a species (enterovirus 71 (ev71), coxsackievirus a16 (ca16), coxsackievirus a5 (ca5) and coxsackievirus a6 (ca6)), of the ev-b species (coxsackievirus b3 (cb3)), and of the ev-c species (poliovirus 1 (pv1)) were detected and analyzed by a neibm (novel evolved immunoglobulin-binding molecule)-based elisa in shanghai blood donors. the serological pr ...201626917423
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
development and evaluation of rapid point-of-care tests for detection of enterovirus 71 and coxsackievirus a16 specific immunoglublin m antibodies.two colloidal gold immunochromatographic assays (cgias) for detection of ev71- and ca16- immunoglobulin m (igm) were developed and evaluated. a total of 1465 sera collected from children with hand, foot, and mouth disease (hfmd), non-hfmd patients and healthy children. the sensitivity of igm cgia tests for ev71 and ca16 were 97.6% (330/338) and 91.6% (296/323) respectively, compared to those who were viral rna positive by pcr. their performances were comparable to those of commercial elisa kits, ...201626912234
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
immunological and biochemical characterizations of coxsackievirus a6 and a10 viral particles.childhood exanthema caused by different serotypes of coxsackievirus (cv-a) and enterovirus a71 (ev-a71) has become a serious global health problem; it is commonly known as hand, foot, and mouth disease (hfmd). current ev-a71 vaccine clinical trials have demonstrated that human antibody responses generated by ev-a71 vaccinations do not cross-neutralize coxsackievirus a16 (cv-a16). an effective multivalent hfmd vaccine is urgently needed. from molecular epidemiological studies in southeast asia, c ...201626899790
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
[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
sirna targeting the 2apro genomic region prevents enterovirus 71 replication in vitro.enterovirus 71 (ev71) is the most important etiological agent of hand, foot, and mouth disease (hfmd) in young children, which is associated with severe neurological complications and has caused significant mortalities in recent hfmd outbreaks in asia. however, there is no effective antiviral therapy against ev71. in this study, rna interference (rnai) was used as an antiviral strategy to inhibit ev71 replication. three small interfering rnas (sirnas) targeting the 2apro region of the ev71 genom ...201626886455
identification and structure-activity relationships of diarylhydrazides as novel potent and selective human enterovirus inhibitors.enterovirus 71 (ev71) plays an important role in hand-foot-and-mouth disease. in this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of sar led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an ec50 value of 0.02 μm against ev71. it is very interesting that this class of diarylhydrazides exhibits activities against a series of human enteroviruses at the picomolar level, including ev ...201626885567
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
hand, foot, and mouth disease in china: modeling epidemic dynamics of enterovirus serotypes and implications for vaccination.hand, foot, and mouth disease (hfmd) is a common childhood illness caused by serotypes of the enterovirus a species in the genus enterovirus of the picornaviridae family. the disease has had a substantial burden throughout east and southeast asia over the past 15 y. china reported 9 million cases of hfmd between 2008 and 2013, with the two serotypes enterovirus a71 (ev-a71) and coxsackievirus a16 (cv-a16) being responsible for the majority of these cases. three recent phase 3 clinical trials sho ...201626882540
clinical efficacy of therapy with recombinant human interferon α1b in hand, foot, and mouth disease with enterovirus 71 infection.a rapid expansion of hfmd with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in china, but no vaccine or antiviral drug is currently available for ev71 infection. this study aims to provide treatment programs for hfmd patients. we conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rhuifn-α1b in hfmd patients with ev71 infection. there were statistical differences in outcomes including the fever clearance time ...201626882102
idarubicin is a broad-spectrum enterovirus replication inhibitor that selectively targets the virus internal ribosomal entry site.enterovirus 71 (ev71) causes life-threatening diseases with neurological manifestations in young children. however, the treatment of ev71 infections remains an unmet medical need. idarubicin (idr) is an anthracycline compound that is used therapeutically for certain types of tumour. in this study, we identified idr as an ev71 inhibitor, which displayed antiviral potency in the submicromolar range and substantially protected cells from the cytopathic effects and cell death caused by ev71 infectio ...201626879094
pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71.some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially coxsackie virus. however, no case of human enterovirus 71 (ev71) associated with pancreatitis has been reported so far. we here report a case of ev71-induced hand-foot-and-mouth disease (hfmd) presenting with pancreatitis in a 2-year-old girl. this is the first report of a patient with acute pancreatitis in hfmd caused by ev71. we treated the patient conservatively with nasogast ...201626877620
carnitine palmitoyl transferase 2 polymorphism may be associated with enterovirus 71 severe infection in a chinese population.genetic polymorphism in the carnitine palmitoyl transferase 2 (cpt2) gene has been reported to be a susceptibility factor in a number of syndromes of acute encephalopathy with various infectious diseases, but evidence of its effect on enterovirus 71 (ev71) infection is lacking. the goal of this study was to examine the relationship between genetic polymorphism of cpt2 and severity of ev71 infection in a chinese population. pcr of five exons of the cpt2 gene was carried out to identify single-nuc ...201626874509
luteoloside acts as 3c protease inhibitor of enterovirus 71 in vitro.luteoloside is a member of the flavonoids family that exhibits several bioactivities including anti-microbial and anti-cancer activities. however, the antiviral activity of luteoloside against enterovirus 71 (ev71) and the potential mechanism(s) responsible for this effect remain unknown. in this study, the antiviral potency of luteoloside against ev71 and its inhibitory effects on 3c protease activity were evaluated. first, we investigated the cytotoxicity of luteoloside against rhabdomyosarcom ...201626870944
risk factors for enterovirus a71 seropositivity in rural indigenous populations in west malaysia.enterovirus a71 (ev-a71), which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. in malaysia, the indigenous rural community (orang asli) has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. this cross-sectional study compared the seroepidemiology of ev-a71 among rural orang asli and urban kuala lumpur populations in west malaysia, and determined the risk factors associat ...201626866912
impact of human enterovirus 71 genotypes in meningoencephalitis in iran.since the importance of poliovirus has diminished, as a result of its elimination in the majority of countries, non-polioviruses are emerging as causative agents of severe central nervous system (cns) involvement. outbreaks of enterovirus 71 (ev71)-associated cns infections have recently been reported in asia, australia, and europe.201526865943
identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of coxsackievirus a16.coxsackievirus a16 (ca16) and enterovirus 71 (ev71) are two main causative pathogens of hand, foot and mouth disease (hfmd). unlike ev71, virulence determinants of ca16, particularly within 5' untranslated region (5'utr), have not been investigated until now. here, a series of nucleotides present in 5'utr of lethal but not in non-lethal ca16 strains were screened by aligning nucleotide sequences of lethal circulating changchun ca16 and the prototype g10 as well as non-lethal shzh05 strains. a re ...201626861413
modification of the length and structure of the linker of n(6)-benzyladenosine modulates its selective antiviral activity against enterovirus 71.very recently, we demonstrated that n(6)-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. the present study is devoted to the structure optimization of another natural compound: n(6)-benzyladenosine. we mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the d-ribose residue. more than 30 analogues of n(6)-benzyladenosi ...201626854380
oblongifolin m, an active compound isolated from a chinese medical herb garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of erp57.there is no effective drug to treat ev71 infection yet. traditional chinese herbs are great resources for novel antiviral compounds. here we showed that oblongifolin m (om), an active compound isolated from garcinia oblongifolia, potently inhibited ev71 infection in a dose dependent manner. to identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. further studies showed that knockdown of ...201626848777
high-throughput characterization of virus-like particles by interlaced size-exclusion chromatography.the development and manufacturing of safe and effective vaccines relies essentially on the availability of robust and precise analytical techniques. virus-like particles (vlps) have emerged as an important and valuable class of vaccines for the containment of infectious diseases. vlps are produced by recombinant protein expression followed by purification procedures to minimize the levels of process- and product-related impurities. the control of these impurities is necessary during process deve ...201626845741
enterovirus 71 transmission by exosomes establishes a productive infection in human neuroblastoma cells.exosomes are small secreted cellular vesicles for intercellular communications which contain proteins, mrnas, and micrornas (mirnas). recent studies have shown that exosomes play an important role in the transmission of infectious agents including hepatitis c virus, human immunodeficiency virus, and so on. however, the role of exosomes in the transfer of enterovirus 71 (ev71) between host cells remains unknown. in this study, we show that the exosomes derived from ev71-infected rhabdomyosarcoma ...201626837894
comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase iii clinical trial.human enterovirus 71 (ev71) is a causative agent of hand, foot, and mouth disease (hfmd). in a previous phase iii trial in children, a human diploid cell-based inactivated ev71 vaccine elicited ev71 specific immune responses and protection against ev71 associated hfmd. this study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. this was a randomized, double-blinded, placebo-controlled, phase iii clinical trial of a human diploid vaccine carr ...201626837471
chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity.enterovirus 71 (ev71) is one of the causative agents of hand, foot, and mouth disease (hfmd), which sometimes leads to severe neurological disease and death in the asia-pacific region. in chinese medicine, hfmd is caused mainly by an accumulation of damp-heat and toxicity in the body. no effective drugs are currently available for the treatment and prevention of ev71 infection. this review summarizes the potential chinese herbal extracts and isolated compounds with antiviral activity against ev7 ...201626834824
protein microarray-mediated detection of antienterovirus antibodies in serum.to utilize prokaryotic gene expression and protein microarray to develop and evaluate a sensitive, accurate protein microarray assay for detecting antienterovirus antibodies in serum samples from patients with hand, foot and mouth disease (hfmd). enterovirus 71 (ev71) and coxsackievirus a16 (ca16), two common causative agents for hfmd, were used for assay development.201626831405
the autophagic machinery in enterovirus infection.the enterovirus genus of the picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus a71, and enterovirus d68. they cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. currently, no effective vaccine is available against enteroviruses except for poliovirus. enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. some enteroviruses spread between cells via ...201626828514
a consistent orally-infected hamster model for enterovirus a71 encephalomyelitis demonstrates squamous lesions in the paws, skin and oral cavity reminiscent of hand-foot-and-mouth disease.enterovirus a71 (ev-a71) causes self-limiting, hand-foot-and-mouth disease (hfmd) that may rarely be complicated by encephalomyelitis. person-to-person transmission is usually by fecal-oral or oral-oral routes. to study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of hfmd and ev-a71 encephalomyelitis. tissues from orally-infected, 2-week-ol ...201626815859
ev71 virus-like particles produced by co-expression of capsid proteins in yeast cells elicit humoral protective response against ev71 lethal challenge.enterovirus 71 (ev71) is the most common causative pathogens of hand, foot and mouth disease (hfmd) associated with severe neurological complications. there is a great need to develop prophylactic vaccine against ev71 infection.201626809443
clinical characteristics and functional motor outcomes of enterovirus 71 neurological disease in children.enterovirus 71 (ev71) causes a spectrum of neurological complications with significant morbidity and mortality. further understanding of the characteristics of ev71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines.201626785318
innate immunity evasion by enteroviruses: insights into virus-host interaction.enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (ev) a71, ev-d68 and rhinovirus. infection with evs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. evs, which are positive-sense single-stranded rna viruses, trigger activation of the host antiviral innate immune responses through pathogen re ...201626784219
a real-time rt-pcr assay for rapid detection of coxsackievirus a10.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) have been the primary causative agents of hand, foot, and mouth disease (hfmd) outbreaks in mainland china in the past. hence, the surveillance of hfmd has mostly focused on these viruses. however, in recent years, coxsackievirus a10 (ca10) has also been associated with the increasing sporadic hfmd cases and outbreaks. therefore, a sensitive assay for rapid detection of the ca10 rna is necessary for disease control. here, we have developed a sp ...201526782393
genome analysis of enterovirus 71 strains differing in mouse pathogenicity.enterovirus 71 (ev71) is a major causative agent of hand, foot, and mouth disease (hfmd) and is occasionally associated with severe neurological diseases. the investigation of virulence determinants of ev71 is rudimentary. therefore, it is important to understand the relationship between ev71 virulence and genomic information. in this study, a series of analyses about full-length genomic sequence were performed on six ev71 strains isolated from hfmd patients with either severe or mild clinical s ...201626781949
disease burden of enterovirus infection in taiwan: implications for vaccination policy.this study aimed to assess the disease burden and economic impacts of human nonpolio enteroviruses (npev) and enterovirus a71 (ev-a71) infection in taiwan.201626768128
the effects of weather factors on hand, foot and mouth disease in beijing.the morbidity and mortality of hand, foot and mouth disease (hfmd) are increasing in beijing, china. previous studies have indicated an association between incidents of hfmd and weather factors. however, the seasonal influence of these factors on the disease is not yet understood, and their relationship with the enterovirus 71 (ev71) and coxsackie virus a16 (cv-a16) viruses are not well documented. we analysed 84,502 hfmd cases from 2008 to 2011 in beijing to explore the seasonal influence of we ...201626755102
validation and evaluation of serological correlates of protection for inactivated enterovirus 71 vaccine in children aged 6-35 months.a primary goal of this study was to establish the serological mechanistic correlate of protection (mcop) for an inactivated enterovirus 71 (ev71) vaccine.201626751765
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
pluripotent human embryonic stem cell derived neural lineages for in vitro modelling of enterovirus 71 infection and therapy.the incidence of neurological complications and fatalities associated with hand, foot & mouth disease has increased over recent years, due to emergence of newly-evolved strains of enterovirus 71 (ev71). in the search for new antiviral therapeutics against ev71, accurate and sensitive in vitro cellular models for preliminary studies of ev71 pathogenesis is an essential prerequisite, before progressing to expensive and time-consuming live animal studies and clinical trials.201626738773
[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
[inactivation of ev71 by exposure to heat and ultraviolet light].enterovirus 71 (ev71) is a major agent of hand, foot and mouth disease that can cause a severe burden of disease to children. to identify an effective method for the control and prevention of ev71, we studied the effect of exposure to heat and ultraviolet (uv) light upon ev71 inactivation. we found that exposure to 50 degrees c could not inactivate the infectivity of ev71. however, exposure to 60 degrees c and 70 degrees c could inactivate ev71 effectively. ev71 could be inactivated after exposu ...201526738287
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
development of novel vaccines against enterovirus-71.the hand, foot and mouth disease is caused by a group of enteroviruses such as enterovirus 71 (ev-a71) and coxsackievirus cv-a5, cv-a8, and cv-a16. mild symptoms of ev-a71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. the lack of vaccines and antiviral drugs against ev-a71 highlights the urgency of developing preventive and treat ...201526729152
interferon-mediated antiviral activities of angelica tenuissima nakai and its active components.angelica tenuissima nakai is a widely used commodity in traditional medicine. nevertheless, no study has been conducted on the antiviral and immune-modulatory properties of an aqueous extract of angelica tenuissima nakai. in the present study, we evaluated the antiviral activities and the mechanism of action of an aqueous extract of angelica tenuissima nakai both in vitro and in vivo. in vitro, an effective dose of angelica tenuissima nakai markedly inhibited the replication of influenza a virus ...201626727903
antiviral effects of reduning injection against enterovirus 71 and possible mechanisms of action.the present study was designed to evaluate the protective effects of reduning injection against enterovirus 71 (ev71) in vero cells and in mice. the vero cells were infected with 100 and 50 tcid50 (50% tissue culture infective dose) of ev71, respectively. the inhibition of reduning injection on cytopathic effect (cpe) was detected. meanwhile, a mouse model produced by intraperitoneal ev71-infection (10(6) tcid50), was used to investigate the protective effects of reduning injection. the total su ...201526721706
[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
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
glucose-6-phosphate dehydrogenase enhances antiviral response through downregulation of nadph sensor hscarg and upregulation of nf-κb signaling.glucose-6-phosphate dehydrogenase (g6pd)-deficient cells are highly susceptible to viral infection. this study examined the mechanism underlying this phenomenon by measuring the expression of antiviral genes-tumor necrosis factor alpha (tnf-α) and gtpase myxovirus resistance 1 (mx1)-in g6pd-knockdown cells upon human coronavirus 229e (hcov-229e) and enterovirus 71 (ev71) infection. molecular analysis revealed that the promoter activities of tnf-α and mx1 were downregulated in g6pd-knockdown cell ...201526694452
innate immunity and immune evasion by enterovirus 71.enterovirus 71 (ev71) is a major infectious disease affecting millions of people worldwide and it is the main etiological agent for outbreaks of hand foot and mouth disease (hfmd). infection is often associated with severe gastroenterological, pulmonary, and neurological diseases that are most prevalent in children. currently, no effective vaccine or antiviral drugs exist against ev71 infection. a lack of knowledge on the molecular mechanisms of ev71 infection in the host and the virus-host inte ...201526694447
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
seroepidemiology of human enterovirus 71 infection among children, cambodia.enterovirus 71 is reported to have emerged in cambodia in 2012; at least 54 children with severe encephalitis died during that outbreak. we used serum samples collected during 2000-2011 to show that the virus had been widespread in the country for at least a decade before the 2012 outbreak.201626690000
a functional polymorphism in ifnar1 gene is associated with susceptibility and severity of hfmd with ev71 infection.enterovirus 71 (ev71), one of the major pathogens of hand, foot and mouth disease (hfmd), results in millions of infections and hundreds of deaths each year in southeast asia. biased infection and variable clinical manifestations of ev71 hfmd indicated that host genetic background played an important role in the occurrence and development of the disease. we identified the mrna profiles of ev71 hfmd patients, which type i interferon (ifn) pathway related genes were down-regulated. four single nuc ...201526679744
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
recent progress towards novel ev71 anti-therapeutics and vaccines.enterovirus 71 (ev71) is a group of viruses that belongs to the picornaviridae family, which also includes viruses such as polioviruses. ev71, together with coxsackieviruses, is widely known for its association with hand foot mouth disease (hfmd), which generally affects children age five and below. besides hfmd, ev71 can also trigger more severe and life-threatening neurological conditions such as encephalitis. considering the lack of a vaccine and antiviral drug against ev71, together with the ...201526670245
studies on inhibition of proliferation of enterovirus-71 by compound yz-ly-0.in recent years, hand-foot-and-mouth disease (hfmd), which is caused by enteroviruses, has emerged as a serious illness. it affects mainly children under the age of five and results in high fatality rates. enterovirus 71 (ev71) is the main causative agent of hfmd in china and currently there are no effective anti-viral drugs available to treat hfmd. in the present study, we screened compounds for inhibition of proliferation of ev71. compound yz-ly-0 stalled the life cycle of ev71. the inhibitor ...201526640412
implications of age-dependent immune responses to enterovirus 71 infection for disease pathogenesis and vaccine design.epidemics of enterovirus serotype 71 (ev71) infection in asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. efforts are underway to develop an effective ev71 vaccine. however, the immunologic correlates of protection against ev71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. severe disease and death typically occur only ...201326619463
relationship between serologic response and clinical symptoms in children with enterovirus 71-infected hand-foot-mouth disease.this study aimed to explore the correlation between clinical symptoms, including rash and fever, and serum antibody reaction to enterovirus 71 (ev71) infection in children hospitalized due to hand-foot-mouth disease (hfmd). from may 2014 to july 2014, a total of 547 children hospitalized due to hfmd in children's hospital of fudan university were enrolled retrospectively. rna levels of ev71 and ca16 in fecal, serum, and cerebrospinal fluid specimens were measured using quantitative real-time rt- ...201526617898
a conserved inhibitory mechanism of a lycorine derivative against enterovirus and hepatitis c virus.enterovirus 71 (ev71) (picornaviridae family) and hepatitis c virus (hcv) (flaviviridae family) are the causative agents of human hand, foot, and mouth disease (hfmd) and hepatitis c, resulting in a severe pandemic involving millions of infections in the asia-pacific region and worldwide. the great impact of ev71 and hcv on public health highlights the need to further our understanding of the biology of these two viruses and develop effective therapeutic antivirals. here, we evaluated a total of ...201526596952
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
[inosine pranobex - cytotoxic activities and effect of on replication of human parainfluenza viruses (hpiv-2, hpiv-4), entroviruses (ca16, ev71) and adenoviruses (hadv-2, hadv-5) in vitro].there are no specific antivirals designed for many viral infections. inosine pranobex (pi) is a purine nucleoside that is involved in a wide variety of intracellular biochemical processes. the mechanism of action in human body is still unclear but numerous studies have demonstrated that this drug inhibits viral replication and exhibit pleiotropic effect. we evaluated in vitro effect of inosine pranobex (pi) on replication of human viruses: parainfluenza viruses (hpiv-2, hpiv-4), entroviruses a ( ...201526591662
association between angiopoietin-2 and enterovirus 71 induced pulmonary edema.to characterize pulmonary edema (pe) fluid induced by enterovirus 71 (ev71) infection, elucidate the relationship between angiopoietin-2 (ang-2) and pe, and explore the pathogenesis of pe.201626590154
engineering enhanced vaccine cell lines to eradicate vaccine-preventable diseases: the polio end game.vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. to enhance vaccine production at reduced costs, a genome-wide rna interference (rnai) screen was performed to identify gene knockdown events that enhanced poliovirus replication. primary screen hits were validated in a vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. multiple single and dual gene silencing events i ...201526581994
host microrna mir-197 plays a negative regulatory role in the enterovirus 71 infectious cycle by targeting the ran protein.enterovirus 71 (ev71), a member of picornaviridae, is associated with severe central nervous system complications. in this study, we identified a cellular microrna (mirna), mir-197, whose expression was downregulated by viral infection in a time-dependent manner. in mir-197 mimic-transfected cells, ev71 replication was inhibited, whereas the internal ribosome entry site (ires) activity was decreased in ev71 strains with or without predicted mir-197 target sites, indicating that mir-197 targets h ...201526581983
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