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enterovirus 71 infection cleaves a negative regulator for viral internal ribosomal entry site-driven translation.far-upstream element-binding protein 2 (fbp2) is an internal ribosomal entry site (ires) trans-acting factor (itaf) that negatively regulates enterovirus 71 (ev71) translation. this study shows that ev71 infection cleaved fbp2. live ev71 and the ev71 replicon (but not uv-inactivated virus particles) induced fbp2 cleavage, suggesting that viral replication results in fbp2 cleavage. the results also showed that virus-induced proteasome, autophagy, and caspase activity co-contribute to ev71-induced ...201323345520
immunogenicity and safety of an enterovirus 71 vaccine in healthy chinese children and infants: a randomised, double-blind, placebo-controlled phase 2 clinical trial.enterovirus 71 (ev71) outbreaks are a socioeconomic burden, especially in the western pacific region. results of phase 1 clinical trials suggest an ev71 vaccine has a clinically acceptable safety profile and immunogenicity. we aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this ev71 vaccine in healthy chinese children.201323352749
inhibition of enterovirus 71 infections and viral ires activity by fructus gardeniae and geniposide.fructus gardeniae has long been used by traditional chinese medical practitioners for its anti-inflammatory, anti-oxidant, anti-tumor and anti-hyperlipidemic characteristics. here we describe our finding that f. gardeniae greatly reduces anti-enterovirus 71 (ev71) activity, resulting in significant decreases in ev71 virus yields, ev71 infections, and internal ribosome entry site activity. we also found that geniposide, a primary f. gardeniae component, inhibited both ev71 replication and viral i ...201323353754
[etiology surveillance of hand-foot-mouth disease in henan province between 2008 and 2011].to understand etiological types and distribution features of hand-foot-mouth disease (hfmd) in henan province between 2008 and 2011.201223363860
[analysis on epidemiology and the main clinical symptoms of viral encephalitis in gansu, 2009-2011].to understand the epidemiological characteristics and the main clinical symptoms of viral encephalitis in gansu.201223363967
structural and functional analysis of coxsackievirus a9 integrin αvβ6 binding and uncoating.coxsackievirus a9 (cva9) is an important pathogen of the picornaviridae family. it utilizes cellular receptors from the integrin αv family for binding to its host cells prior to entry and genome release. among the integrins tested, it has the highest affinity for αvβ6, which recognizes the arginine-glycine-aspartic acid (rgd) loop present on the c terminus of viral capsid protein, vp1. as the atomic model of cva9 lacks the rgd loop, we used surface plasmon resonance, electron cryo-microscopy, an ...201323365426
[comparison of different molecular assays for the rapid detection of enterovirus 71 (ev71)].molecular detection of enterovirus (ev)71 rna based on pcr methods is a quick and sensitive approach. at present, different pcr-based methods for ev71 rna detection are available, but comparisons of results obtained using different approaches are limited. this study is to compare the analytical sensitivity and specificity of different real-time reverse transcription-polymerase chain reaction (rrt-pcr) and conventional reverse transcription-polymerase chain reaction (crt-pcr) assays for enterovir ...201223367568
[genetic characteristics of enterovirus 71 vp1 and epidemiology of hand-foot-mouth disease in xinxiang in 2011].the study was performed to examine the enterovirus 71(ev71) vp1 genetic feature and the epidemiology of hand-foot-mouth disease (hfmd) in xinxiang in 2011. real-time rt-pcr was used for the detection of pan-enterovirus, coxsackievirus a 16(ca16) and ev71 from stool specimens of hfmd. the vp1 region was amplified from 10 ev71 positive samples and the products were sequenced. ev71 genotypes were characterized by homology and phylogenetic tree analyses. additionally, epidemic data of xinxiang hfmd ...201223367569
study of the integrated immune response induced by an inactivated ev71 vaccine.enterovirus 71 (ev71), a major causative agent of hand-foot-and-mouth disease (hfmd), causes outbreaks among children in the asia-pacific region. a vaccine is urgently needed. based on successful pre-clinical work, phase i and ii clinical trials of an inactivated ev71 vaccine, which included the participants of 288 and 660 respectively, have been conducted. in the present study, the immune response and the correlated modulation of gene expression in the peripheral blood mononuclear cells (pbmcs) ...201323372725
development of a sensitive and specific epitope-blocking elisa for universal detection of antibodies to human enterovirus 71 strains.human enterovirus 71 (ev71) is a common cause of hand, foot and mouth disease (hfmd) in young children. it is often associated with severe neurological diseases and mortalities in recent outbreaks across the asia pacific region. currently, there is no efficient universal antibody test available to detect ev71 infections.201323383215
hexamethonium reverses the lethal cardiopulmonary damages in a rat model of brainstem lesions mimicking fatal enterovirus 71 encephalitis.among enterovirus 71 infections, brainstem encephalitis progressing abruptly to cardiac dysfunction and pulmonary edema causes rapid death within several hours. however, no currently known early indicators and treatments can monitor or prevent the unexpectedly fulminant course. we investigate the possible mechanisms and treatment of fatal enterovirus 71 infections to prevent the abrupt progression to cardiac dysfunction and pulmonary edema by using an animal model.201323388515
3c protease of enterovirus 68: structure-based design of michael acceptor inhibitors and their broad-spectrum antiviral effects against picornaviruses.we have determined the cleavage specificity and the crystal structure of the 3c protease of enterovirus 68 (ev68 3c(pro)). the protease exhibits a typical chymotrypsin fold with a cys...his...glu catalytic triad; its three-dimensional structure is closely related to that of the 3c(pro) of rhinovirus 2, as well as to that of poliovirus. the phylogenetic position of the ev68 3c(pro) between the corresponding enzymes of rhinoviruses on the one hand and classical enteroviruses on the other prompted ...201323388726
recombinant baculovirus associated with bilosomes as an oral vaccine candidate against hev71 infection in mice.human enterovirus 71 (hev71) is one of the major pathogen responsible for hand, foot and mouth disease (hfmd). currently no effective vaccine or antiviral drugs are available. like poliovirus, ev71 is transmitted mainly by the feco-oral route. to date the majority of the studied ev71 vaccine candidates are administered parenterally. injectable vaccines induce good systemic immunity but mucosal responses are often unsatisfactory, whereas mucosal vaccines provide both systemic and mucosal immunity ...201323390538
efficacy of alcohols and alcohol-based hand disinfectants against human enterovirus 71.human enterovirus 71 (hev71) infections are a significant public health threat in the asia-pacific region and occasionally cause severe neurological complications and even death in children. although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against hev71 are still lacking.201323399482
antiviral activity of isatis indigotica root-derived clemastanin b against human and avian influenza a and b viruses in vitro.clemastanin b, 7s,8r,8'r-(-)-lariciresinol-4,4'-bis-o-β-d-glucopyranoside, is one of the major lignans extracted from isatis indigotica root (iir). in this study, the anti-influenza activities of clemastanin b were evaluated in vitro. clemastanin b was found to inhibit different subtypes of human (h1n1, including swine-origin h1n1; h3n2 and influenza b) and avian influenza viruses (h6n2, h7n3, h9n2) at different magnitudes of activity (ic50 0.087-0.72 mg/ml) while this compound was inactive agai ...201323403777
subneutralizing antibodies to enterovirus 71 induce antibody-dependent enhancement of infection in newborn mice.antibody-dependent enhancement (ade) of virus infections can be induced by subneutralizing concentrations of specific antibodies. we recently demonstrated ade in human monocytes infected with enterovirus 71 (ev71). the current study was designed to extend these observations by determining the effect of ade on the pathogenesis of ev71 infection in newborn mice. we compared the clinical manifestations, mortality, virus titer, histopathology, and serum levels of cytokines and chemokines in newborn ...201323408291
phylogenetic analysis of enterovirus 71 circulating in beijing, china from 2007 to 2009.the major pathogens of hand, foot and mouth disease (hfmd) in beijing, china from 2007 to 2009 were identified in this study. a total of 186 hfmd cases were included, and 136 cases (73%) were positive for enterovirus (ev). in 2007, 75% (27/36) were coxsackievirus a16 (ca16) positive and 19% (7/36) were enterovirus 71 (ev71) positive cases. however, ev71 was the predominant virus in 2008, when 56% (31/55) of the cases were positive for ev71 and 22% (12/55) were positive for ca16. in 2009, ev71 an ...201323418551
the interplays between autophagy and apoptosis induced by enterovirus 71.enterovirus 71 (ev71) is the causative agent of human diseases with distinct severity, from mild hand, foot and mouth disease to severe neurological syndromes, such as encephalitis and meningitis. the lack of understanding of viral pathogenesis as well as lack of efficient vaccine and drugs against this virus impedes the control of ev71 infection. ev71 virus induces autophagy and apoptosis; however, the relationship between ev71-induced autophagy and apoptosis as well as the influence of autopha ...201323437282
complete genome analysis of the c4 subgenotype strains of enterovirus 71: predominant recombination c4 viruses persistently circulating in china for 14 years.genetic recombination is a well-known phenomenon for enteroviruses. to investigate the genetic characterization and the potential recombination of enterovirus 71 (ev71) circulating in china, we determined the 16 complete genome sequences of ev71 isolated from hand foot mouth disease (hfmd) patients during the large scale outbreak and non-outbreak years since 1998 in china. the full length genome sequences of 16 chinese ev71 in present study were aligned with 186 genome sequences of ev71 availabl ...201323441179
hand, foot, and mouth disease: current scenario and indian perspective.hand, foot, and mouth disease (hfmd), first reported in new zealand in 1957 is caused by coxsackievirus a16 (cva16) and human enterovirus 71 (hev71) and occasionally by coxsackievirus a4-a7, a9, a10, b1-b3, and b5. this is characterized by erythematous papulo vesicular eruptions over hand, feet, perioral area, knees, buttocks and also intraorally mostly in the children. hfmd has been known for its self limiting course. only small scale outbreaks have been reported from united states, europe, aus ...201323442455
enterovirus 71 causes hand, foot and mouth disease outbreak in cambodia. 201223448647
human scarb2 transgenic mice as an infectious animal model for enterovirus 71.enterovirus 71 (ev71) and coxsackievirus (cva) are the most common causative factors for hand, foot, and mouth disease (hfmd) and neurological disorders in children. lack of a reliable animal model is an issue in investigating ev71-induced disease manifestation in humans, and the current clinical therapies are symptomatic. we generated a novel ev71-infectious model with hscarb2-transgenic mice expressing the discovered receptor human scarb2 (hscarb2). the challenge of hscarb2-transgenic mice wit ...201323451246
neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype c4 inhibit infection at pre- and post-attachment steps.enterovirus 71 (ev71) is a major causative agent of hand, foot and mouth disease, which has been prevalent in asia-pacific regions, causing significant morbidity and mortality in young children. antibodies elicited by experimental ev71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. however, how neutralizing antibodies inhibit infection in vitro remains unclear.201323451250
glycyrrhizic acid as the antiviral component of glycyrrhiza uralensis fisch. against coxsackievirus a16 and enterovirus 71 of hand foot and mouth disease.the radices of glycyrrhiza uralensis fisch. and herbal preparations containing glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in china. glycyrrhizic acid (ga) is considered the principal component in glycyrrhiza spp. with a wide spectrum of antiviral activity.201323454684
cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.recently, enterovirus 71 (ev71) has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in asian children with unknown mechanism. ev71 has one single serotype but can be phylogenetically classified into 3 main genogroups (a, b and c) and 11 genotypes (a, b1∼b5 and c1∼c5). in taiwan, nationwide ev71 epidemics with different predominant genotypes occurred in 1998 (c2), 2000-2001 (b4), 2004-2005 (c4), and 2008 (b5). in this study, sera were collected to measur ...201323459633
the antiviral effect of 7-hydroxyisoflavone against enterovirus 71 in vitro.enterovirus 71 (ev71) is the major causative agent of hand foot and mouth disease. and ev71 causes epidemics worldwide, particularly in the asia-pacific region. unfortunately, currently there is no approved vaccine or antiviral drug for ev71-induced disease prevention and therapy. in screening for anti-ev71 candidates, we found that 7-hydroxyisoflavone was active against ev71. 7-hydroxyisoflavone exhibited strong antiviral activity against three different ev71 strains. the 50% inhibitory concent ...201323464760
human microrna hsa-mir-296-5p suppresses enterovirus 71 replication by targeting the viral genome.enterovirus 71 (ev71) has emerged as a major cause of neurological disease following the near eradication of poliovirus. accumulating evidence suggests that mammalian micrornas (mirnas), a class of noncoding rnas of 18 to 23 nucleotides (nt) with important regulatory roles in many cellular processes, participate in host antiviral defenses. however, the roles of mirnas in ev71 infection and pathogenesis are still unclear. here, hsa-mir-296-5p expression was significantly increased in ev71-infecte ...201323468506
display of the viral epitopes on lactococcus lactis: a model for food grade vaccine against ev71.in this study, we have developed a system for display of antigens of enterovirus type 71 (ev71) on the cell surface of l. lactis. the viral capsid protein (vp1) gene from a local viral isolate was utilized as the candidate vaccine for the development of oral live vaccines against ev71 using l. lactis as a carrier. we expressed fusion proteins in e. coli and purified fusion proteins were incubated with l. lactis. we confirmed that mice orally fed with l. lactis displaying these fusion proteins on ...201323476790
crystal structure of enterovirus 71 rna-dependent rna polymerase complexed with its protein primer vpg: implication for a trans mechanism of vpg uridylylation.picornavirus rna replication is initiated by vpg uridylylation, during which the hydroxyl group of the third tyrosine residue of the virally encoded protein vpg is covalently linked to two ump molecules by rna-dependent rna polymerase (rdrp; also known as 3d(pol)). we previously identified site 311, located at the base of the palm domain of the enterovirus 71 (ev71) rdrp, to be the site for ev71 vpg binding and uridylylation. here we report the crystal structure of ev71 3d(pol) complexed with vp ...201323487447
structure of human enterovirus 71 in complex with a capsid-binding inhibitor.human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. as of now, no cure is available for enterovirus 71 infections. small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. here we report a 3.2-å-resolution x-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibit ...201323509286
molecular epidemiology of human enterovirus 71 strains in the nanchang region of china in 2011.hand, foot, and mouth disease (hfmd) is caused by enteroviruses, most commonly enterovirus 71 (ev71) and coxsackievirus a16 (ca16). in general, ev71 infection is more likely to induce severe complications and mortality than other enterovirus infections. the present study focuses on the molecular epidemiology of human ev71 strains in the nanchang region of china in 2011. overall, 651 specimens (throat or rectal swabs) were collected, and one-step reverse transcriptase-polymerase chain reaction wa ...201323514913
calcium flux and calpain-mediated activation of the apoptosis-inducing factor contribute to enterovirus 71-induced apoptosis.enterovirus 71 (ev71) is a causative agent of an array of childhood diseases with severe neurological manifestations implicated. ev71 infection is known to induce caspase-dependent apoptosis in cell cultures and animal models. however, whether an alternative apoptotic pathway independent of caspase activation can be triggered by ev71 infection has not been explored. in this study, we showed that calcium (ca²⁺)-activated calpains are capable of mediating caspase-independent pathway activation dur ...201323515028
neutralization of five subgenotypes of enterovirus 71 by taiwanese human plasma and taiwanese plasma derived intravenous immunoglobulin.enterovirus 71 (ev71) commonly occurs in children, causing hand, foot and mouth disease (hfmd) in about 29% of patients. studies have suggested that patients develop meningitis and encephalopathy with a mortality rate of 4-26%. ev71 subgenotypes including b4, b5, c2, c4 and c5 have caused hfmd epidemics in taiwan. in terms of therapeutical strategy, intravenous immunoglobulin (ivig) has been shown to improve patient conditions. in this study, the ev71 neutralizing titer was evaluated in 75 human ...201323515089
impact of extracorporeal membrane oxygenation support on clinical outcome of pediatric patients with acute cardiopulmonary failure: a single-center experience.conventional therapy against acute pediatric cardiopulmonary failure (apcpf) caused by a variety of disease entities remains unsatisfactory with extremely high morbidity and mortality. for refractory apcpf, extracorporeal membrane oxygenation (ecmo) is one of the last resorts.201423515152
synthesis and antiviral activity of n-phenylbenzamide derivatives, a novel class of enterovirus 71 inhibitors.a series of novel n-phenylbenzamide derivatives were synthesized and their anti-ev 71 activities were assayed in vitro. among the compounds tested, 3-amino-n-(4-bromophenyl)-4-methoxybenzamide (1e) was active against the ev 71 strains tested at low micromolar concentrations, with ic50 values ranging from 5.7 ± 0.8-12 ± 1.2 μm, and its cytotoxicity to vero cells (tc50 = 620 ± 0.0 μm) was far lower than that of pirodavir (tc50 = 31 ± 2.2 μm). based on these results, compound 1e is a promising lead ...201323519203
association of interleukin-17f gene polymorphism with enterovirus 71 encephalitis in patients with hand, foot, and mouth disease.enterovirus 71 (ev71) is one of the common pathogenic agents of hand, foot, and mouth disease (hfmd) and is associated with severe complications including encephalitis. interleukin (il)-17f plays an important role in tissue inflammation by inducing release of proinflammatory cytokines and chemokines. we investigated the association between ev71 encephalitis and of il-17f 7488t/c (rs763780) gene polymorphism, which is known to cause a his-to-arg substitution at amino acid 161. the study was perfo ...201323519962
adaptation of enterovirus 71 to adult interferon deficient mice.non-polio enteroviruses, including enterovirus 71 (ev71), have caused severe and fatal cases of hand, foot and mouth disease (hfmd) in the asia-pacific region. the development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. in this study, a mouse adapted ev71 strain was produced by conducting serial passages through a129 (α/β interferon (ifn) receptor deficient) and ag129 (α/β, γ ifn receptor deficient) mice. a b2 sub genotype of ...201323527208
a new factor influencing pathogen detection by molecular assay in children with both mild and severe hand, foot, and mouth disease.this study aimed to find novel information concerning pathogen detection and some probable coinfection factors in hand, foot, and mouth disease (hfmd). in this study, 1104 clinically diagnosed hfmd patients were included. enterovirus 71 (ev71), coxsackievirus a16 (ca16), and 14 different respiratory pathogens were examined from nasopharyngeal swabs using polymerase chain reaction (pcr) or reverse transcriptase pcr (rt-pcr). to evaluate the immune activation in hfmd patients, 8 cytokines and igm ...201323535205
beta-actin variant is necessary for enterovirus 71 replication.enterovirus 71 (ev71) is one of the main etiological agents of the hand, foot and mouth disease (hfmd) and has been known to cause fatal neurological complications such as herpangina, aseptic meningitis, poliomyelitis-like paralysis and encephalitis. ev71 is endemic in the asia-pacific region and causes occasional epidemics. in order to better understand ev71 infection, we compared the proteome between ev71-susceptible and ev71-resistant human rhabdomyosarcoma (rd) cell line. we found significan ...201323535377
a phase i, randomized, open-label study to evaluate the safety and immunogenicity of an enterovirus 71 vaccine.large-scale outbreaks of enterovirus 71 (ev71) infections have occurred in asia-pacific regions. severe complications include encephalitis and poliomyelitis-like paralysis, cardiopulmonary collapse, and death, necessitating an effective vaccine against ev71.201323541623
[isolation and sequence analysis on virus of hfmd with encephalitis in yantal city].to learn about the pathogen spectrum and genetic characterization of hfmd with encephalitis in yantai city.201223547453
[detection the pathogens and analysis the clinical characteristics in children with hand, foot and mouth disease in shanghai during 2009-2011].to investigate the epidemic characteristics of etiological agents and analyze the clinic differences in children with hand, foot and mouth diseases in shanghai.201223547454
a laboratory evaluation of medicinal herbs used in china for the treatment of hand, foot, and mouth disease.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the causative agents of hand, foot, and mouth disease (hfmd). during recent epidemics of hfmd in china, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. there have been no microbiological studies to validate their usefulness for hfmd. we selected 12 commonly used herbs for hfmd from government recommended guidelines as well as published reports and tested fo ...201323554831
enterovirus 71 protease 2apro targets mavs to inhibit anti-viral type i interferon responses.enterovirus 71 (ev71) is the major causative pathogen of hand, foot, and mouth disease (hfmd). its pathogenicity is not fully understood, but innate immune evasion is likely a key factor. strategies to circumvent the initiation and effector phases of anti-viral innate immunity are well known; less well known is whether ev71 evades the signal transduction phase regulated by a sophisticated interplay of cellular and viral proteins. here, we show that ev71 inhibits anti-viral type i interferon (ifn ...201323555247
the enterovirus 71 a-particle forms a gateway to allow genome release: a cryoem study of picornavirus uncoating.since its discovery in 1969, enterovirus 71 (ev71) has emerged as a serious worldwide health threat. this human pathogen of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. upon binding to a host receptor on the cell surface, the virus begins a two-step uncoating process, first forming an expanded, altered "a-particle", which is primed for genome release. in a second step after endocyto ...201323555253
chlorine dioxide inactivation of enterovirus 71 in water and its impact on genomic targets.to control the waterborne transmission of enterovirus 71(ev71), which is associated with hand foot and mouth disease (hfmd), it is essential to know the inactivation effectiveness of disinfectants on ev71 in water. in this article, we present a comparative analysis of the effects on ev71 following exposure to chlorine dioxide (clo2) under different doses, ph, and temperature conditions. we show that the ev71 exhibited strong resistance to clo2 (more than the ms2 standard) and that ct value range ...201323560857
immune responses to baculovirus-displayed enterovirus 71 vp1 antigen.the increased distribution and neurovirulence of enterovirus 71 is an important health threat for young children in asia pacific. vaccine design has concentrated on inactivated virus with the most advanced undergoing phase iii clinical trials. by using a subunit vaccine approach, production costs could be reduced by lowering the need for biocontainment. in addition, novel mutations could be rapidly incorporated to reflect the emergence of new enterovirus 71 subgenogroups. to circumvent the probl ...201323560917
mri characteristics of brainstem encephalitis in hand-foot-mouth disease induced by enterovirus type 71--will different mri manifestations be helpful for prognosis?the mri characteristics of 21 hfmd patients with brainstem encephalitis resulting from ev71 infection were examined to identify lesion patterns helpful in disease classification and prognosis. the author reviewed the clinical and mri data of 21 children with brainstem encephalitis infected during the ev71 outbreak in hainan, china from may 2008 to september 2010. thirteen cases of brainstem encephalitis were classified as type i based on unilateral or bilateral symmetrical patch-like hyperintens ...201323561930
iridoid and bis-iridoid glucosides from the fruit of gardenia jasminoides.three new iridoid glucosides, 6″-o-trans-feruloylgenipin gentiobioside (1), 2'-o-trans-caffeoylgardoside (2), jasmigeniposide a (3), and one new bis-iridoid glucoside, jasmigeniposide b (4), along with six known analogues (5-10), were isolated from the fruit of gardenia jasminoides. their structures were established on the basis of spectroscopic analyses and chemical methods. anti-virus activity of isolated compounds were evaluated in vitro and only compound 9 showed moderate inhibitory activity ...201323567862
a safety study of inactivated enterovirus 71 vaccine.enterovirus 71 (ev71) is one of the major causative agents for hand, foot and mouth disease (hfmd) in childhood. nowadays, hfmd or ev71 infections have already become an important public health issue throughout the world. vaccination may be the most effective measure to control the transmission of the virus. therefore, to pave ev71 vaccine into human clinical trial, in the present study a comprehensive preclinical safety assessment of inactivated ev71 vaccine including single- and repeat-dose to ...201323571172
complete genome sequencing and analysis of six enterovirus 71 strains with different clinical phenotypes.hand, foot and mouth diseases (hfmd) caused by enterovirus 71(ev71) presents a broad spectrum of clinical manifestations ranging from mild febrile disease to fatal neurolocal disease. however, the mechanism of virulence is unknown.201323577963
rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.the development of vaccines against infectious diseases represents one of the most important contributions to medical science. however, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. the biomimetic nucleating p ...201323589862
emerging viral infections.this review highlights research and development in the field of emerging viral causes of encephalitis over the past year.201323591683
microrna-23b inhibits enterovirus 71 replication through downregulation of ev71 vpl protein.enterovirus 71 (ev71) is one of the causative pathogens of hand-foot-and-mouth disease and effective antiviral agents and vaccines against this virus have, to date, not been available. micrornas (mirnas) are a recently discovered class of rnas with the function of post-transcriptional gene expression regulation. it has been demonstrated that mirnas play important roles in the complicated interaction network between virus and host, while few studies have explored the role of mirnas in ev71 infect ...201323594713
elevation of human leukocyte antigen-g expression is associated with the severe encephalitis associated with neurogenic pulmonary edema caused by enterovirus 71.enterovirus 71 (ev71) infection can develop devastating clinical outcomes such as brain stem encephalitis (be) and pulmonary edema (pe). alteration of human leukocyte antigen-g (hla-g) expression or cytokine production was considered playing important roles in virus-related pathogenesis. however, clinical relevance of hla-g in ev71 infection remains unknown. in the current study, patients were stratified by disease severity as be (n = 107) and pe (n = 18). hla-g expression on peripheral blood mo ...201423605689
conformational plasticity of the 2a proteinase from enterovirus 71.the 2a proteinase (2a(pro)) is an enterovirally encoded cysteine protease that plays essential roles in both the processing of viral precursor polyprotein and the hijacking of host cell translation and other processes in the virus life cycle. crystallographic studies of 2a(pro) from enterovirus 71 (ev71) and its interaction with the substrate are reported here. ev71 2a(pro) was comprised of an n-terminal domain of a four-stranded antiparallel β sheet and a c-terminal domain of a six-stranded ant ...201323616646
hepatic damage caused by coxsackievirus b3 is dependent on age-related tissue tropisms associated with the coxsackievirus-adenovirus receptor.coxsackievirus b (cvb) and enterovirus 71 (ev71) are important causes of severe enteroviral diseases in neonates or young children in taiwan. cvb can cause fulminant hepatitis, myocarditis or meningoencephalitis. this study was designed to explore the role of coxsackievirus-adenovirus receptor (car) in the pathogenesis of cvb3-infected hepatocytes via in vitro and mice studies. cvb3 (cvb3/2630) was isolated from liver tissue of a neonate with fulminant hepatitis. cell lines a549, hela, hep2 and ...201323620416
inflammatory, vascular, and infectious myelopathies in children.acute nontraumatic myelopathies of childhood include inflammatory, infectious, and vascular etiologies. inflammatory immune-mediated disorders of the spinal cord can be categorized as idiopathic isolated transverse myelitis, neuromyelitis optica, and multiple sclerosis. in recent years, human t-cell lymphotropic virus type 1, west nile virus, enterovirus-71, and lyme disease have been increasingly recognized as infectious etiologies of myelopathy, and poliomyelitis remains an important etiology ...201323622308
[transmission and prevalence patterns of c4a evolutionary lineage of human enterovirus 71 circulating in mainland of china, 2008-2010].to understand the evolutionary relationship between the c4a evolutionary lineage of human enterovirus 71 (hev71) strains circulating in mainland of china during 2008-2010 and 2008 fuyang strains and study the prevalence and transmission patterns of 2008 fuyang strains.201223627020
[association of hla-g 14bp gene polymorphisms and plasma shla-g level with susceptibility to ev71 infection in children].explore the relationship between the hla-g 14bp insertion/deletion polymorphism and the infection of enterovirus 71 (ev71) for children.201223627021
novel substituted heteroaromatic piperazine and piperidine derivatives as inhibitors of human enterovirus 71 and coxsackievirus a16.a series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein vp1. the preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against ev71 and coxsackievirus a16 with low cytotoxicity.201323629759
hand, foot, and mouth disease caused by coxsackievirus a6, thailand, 2012.in thailand, hand, foot, and mouth disease (hfmd) is usually caused by enterovirus 71 or coxsackievirus a16. to determine the cause of a large outbreak of hfmd in thailand during june-august 2012, we examined patient specimens. coxsackievirus a6 was the causative agent. to improve prevention and control, causes of hfmd should be monitored.201323631943
structures of enterovirus 71 3c proteinase (strain e2004104-tw-cdc) and its complex with rupintrivir.the crystal structure of 3c proteinase (3c(pro)) from enterovirus 71 (ev71) was determined in space group c2221 to 2.2 å resolution. the fold was similar to that of 3c(pro) from other picornaviruses, but the difference in the β-ribbon reported in a previous structure was not observed. this β-ribbon was folded over the substrate-binding cleft and constituted part of the essential binding sites for interaction with the substrate. the structure of its complex with rupintrivir (ag7088), a peptidomim ...201323633597
structures of the procapsid and mature virion of enterovirus 71 strain 1095.enterovirus 71 (ev71) is an important emerging human pathogen with a global distribution and presents a disease pattern resembling poliomyelitis with seasonal epidemics that include cases of severe neurological complications, such as acute flaccid paralysis. ev71 is a member of the picornaviridae family, which consists of icosahedral, nonenveloped, single-stranded rna viruses. here we report structures derived from x-ray crystallography and cryoelectron microscopy (cryo-em) for the 1095 strain o ...201323637404
the development and application of the two real-time rt-pcr assays to detect the pathogen of hfmd.large-scale hand, foot, and mouth disease (hfmd) outbreaks have frequently occurred in china since 2008, affecting more than one million children and causing several hundred children deaths every year. the pathogens of hfmd are mainly human enteroviruses (hevs). among them, human enterovirus 71 (hev71) and coxsackievirus a16 (cva16) are the most common pathogens of hfmd. however, other hevs could also cause hfmd. to rapidly detect hev71 and cva16, and ensure detection of all hevs causing hfmd, t ...201323637836
chebulagic acid, a hydrolyzable tannin, exhibited antiviral activity in vitro and in vivo against human enterovirus 71.human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. presently, no vaccines or antiviral drugs have been clinically available to employ against ev71. in this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an ic50 of 12.5 μg/ml. the utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to effi ...201323644889
mda5 plays a crucial role in enterovirus 71 rna-mediated irf3 activation.induction of type-i interferons (ifns), ifn-α/β, is crucial to innate immunity against rna virus infection. cytoplasmic retinoic acid-inducible gene i (rig-i)-like receptors, including rig-i and melanoma differentiation-associated gene 5 (mda5), are critical pathogen sensors for activation of type-i ifn expression in response to rna virus infection. mda5 is required for type-i ifn expression in mouse models in response to infection by picornaviruses, such as encephalomyocarditis virus (emcv) and ...201323650567
inhibition of enveloped viruses infectivity by curcumin.curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (ha) activity. this study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. in all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. in contrast, the nonenveloped enterovirus 71 r ...201323658730
enterovirus 71 encephalitis: a new vaccine on the horizon? 201323668563
robust antiviral responses to enterovirus 71 infection in human intestinal epithelial cells.enterovirus 71 (ev71) is a single-stranded rna virus that belongs to picornaviridae family. it causes the hand-foot-and-mouth disease and fatal neurological diseases in young children and infants. the mechanism of ev71 pathogenesis remains obscure. the intestinal tract is the initial site of ev71 replication, but no or only mild gastrointestinal symptoms are observed clinically, suggesting that host immune responses of the intestinal epithelium to ev71 may be unique, which, however, remains rare ...201323685430
milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3b) is associated with rapid mortality in children. in a small pilot study, we found that milrinone reduced early mortality compared with historical controls. this prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3b enterovirus 71 infections.201323685637
substituted 3-benzylcoumarins as allosteric mek1 inhibitors: design, synthesis and biological evaluation as antiviral agents.in order to find novel antiviral agents, a series of allosteric mek1 inhibitors were designed and synthesized. based on docking results, multiple optimizations were made on the coumarin scaffold. some of the derivatives showed excellent mek1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the erk pathway in a cellular assay. these compounds also significantly inhibited virus (ev71) replication in hek293 and rd cells. several compounds showed poten ...201323698055
human igg subclasses against enterovirus type 71: neutralization versus antibody dependent enhancement of infection.the emerging human enterovirus 71 (ev71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. human intravenous immunoglobulin (ivig) is clinical used in treating severe ev71 infections. however, the discovery of antibody dependent enhancement (ade) of ev71 infection illustrates the complex roles of antibody in controlling ev71 infection. in this study, to identify the distinct role of each igg subclass on neutralization and enhancement of ev ...201323700449
analysis and solution of false-positives when testing cva16 sera using an antibody assay against the ev71 virus.hand, foot and mouth disease (hfmd) in humans is caused mainly by enterovirus 71(ev71) and coxsackievirus a16 (cva16). ev71 is associated with severe hfmd cases but not cva16. use of igm-capture enzyme-linked immunosorbent assay (elisa) is important for the early diagnosis of ev71 infection, but cross-reactivity of the anti-cva16 igm antibody with ev71 produces false-positive results. in this report, we designed a new ev71 igm-capture elisa method using the ev71 vp1 peptide instead of the ev71 v ...201323707400
heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly.molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in human enterovirus 71 (ev71). here we describe the specific association of heat shock protein-90-beta (hsp90β), but not alpha form (hsp90α), with ev71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. the reduction of the hsp90β protein using rna inter ...201323711381
[establishment of ev71 animal models with 2-week-old balb/c mice].animal model is very important for anti-ev71 (enterovirus 71) drug and vaccine development. 1-day-old suckling ev71 mouse model is the main in vivo model used in china. 1-day-old suckling ev71 mouse is too small to perform antiviral experiment. and the route of administration and dosage capacity are also restricted. a strong virulence ev71 virus strain was selected after screening from five ev71 strains with 1-day-old suckling mice. a mouse-adapted ev71 strain with increased virulence in 12-day- ...201323724645
efficacy, safety, and immunology of an inactivated alum-adjuvant enterovirus 71 vaccine in children in china: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.a vaccine for enterovirus 71 (ev71) is needed to address the high burden of disease associated with infection. we assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant ev71 vaccine.201323726161
virus-like particles for enterovirus 71 produced from saccharomyces cerevisiae potently elicits protective immune responses in mice.human enterovirus 71 (ev71) is recognized as the leading causative agent of hand-foot-and-mouth disease (hfmd) in the asia-pacific region in recent years. there are still no approved antiviral drugs or vaccines against ev71 infection yet. in this study, we have developed an advanced platform for production of the virus-like particles (vlps) for ev71 in saccharomyces cerevisiae by co-expressing p1 and 3cd genes of ev71. these vlps exhibited similar morphology and protein composition as ev71 empty ...201323726823
high-affinity interaction of hnrnp a1 with conserved rna structural elements is required for translation and replication of enterovirus 71.human enterovirus 71 (ev71) is an emerging pathogen of infectious disease and a serious threat to public health. currently, there are no antivirals or vaccines to slow down or prevent ev71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. ev71 uses a type i internal ribosome entry site (ires) to recruit the 40s ribosomal subunit via a pathway that requires the cytoplasmic localization of hnrnp a1, which acts as an ires trans-activating fa ...201323727900
development of a sandwich elisa for the quantification of enterovirus 71.since 2008, enterovirus 71 (ev71) has been responsible for high-mortality seasonal epidemics of hand, foot and mouth disease in china. currently many groups in the world are in the process of developing ev71 vaccines to combat this deadly disease. we have developed three ev71-specific monoclonal antibodies, and in this study we report the establishment of a fast and cost-effective sandwich elisa kit for measurement of virus concentration in ev71 vaccines using a pair of mouse anti-ev71 monoclona ...201423728855
progress on the research and development of inactivated ev71 whole-virus vaccines.the prevalence of diseases caused by ev71 infection has become a serious public health problem in the western pacific region. due to a lack of effective treatment options, controlling ev71 epidemics has mainly focused on the research and development (r&d) of ev71 vaccines. thus far, five organizations have completed pre-clinical studies focused on the development of inactivated ev71 whole-virus vaccines, including vaccine strain screening, process optimization, safety and immunogenicity evaluati ...201323744508
enterovirus 71 receptors: promising drug targets? 201323750725
development and evaluation of a pseudovirus-luciferase assay for rapid and quantitative detection of neutralizing antibodies against enterovirus 71.the level of neutralizing antibodies (ntab) induced by vaccine inoculation is an important endpoint to evaluate the efficacy of ev71 vaccine. in order to evaluate the efficacy of ev71 vaccine, here, we reported the development of a novel pseudovirus system expression firefly luciferase (pvla) for the quantitative measurement of ntab. we first evaluated and validated the sensitivity and specificity of the pvla method. a total of 326 serum samples from an epidemiological survey and 144 serum speci ...201323755115
[analysis on molecular epidemiological features of enterovirus type 71 in guizhou province, 2008-2011].to study the genotype and molecular epidemiological features of enterovirus type 71 (ev71) in guizhou province. the hand-foot-mouth disease(hfmd) patients since 2008 in guizhou province were surveyed. ev71 rna positive samples, including mild cases, death cases and cases of serious conditions, were used for subsequent cell culture and sequencing of vp1 complete gene. genotypes were compared between domestic and foreign epidemic strains. the results showed that the main pathogenwas ev71 subtype c ...201323757849
[progress in research of new human enterovirus types].more and more new human enteroviruses (hevs) types were identified with the broad application of the molecular serotyping methods for enteroviruses. since enterovirus 71 (ev71) was first reported in 1969, numerous epidemic outbreaks associated with new enteroviruses have occurred all around the world, and pose a significant threat to public health . the epidemics of hand, foot and mouth disease (hfmd) caused by ev71 infection in china have raised great concern of global scholars. this paper revi ...201323757855
caveolar endocytosis is required for human psgl-1-mediated enterovirus 71 infection.enterovirus 71 (ev71) causes hand, foot, and mouth disease and severe neurological disorders in children. human scavenger receptor class b member 2 (hscarb2) and p-selectin glycoprotein ligand-1 (psgl-1) are identified as receptors for ev71. the underling mechanism of psgl-1-mediated ev71 entry remains unclear. the endocytosis required for ev71 entry were investigated in jurkat t and mouse l929 cells constitutively expressing human psgl-1 (psgl-1-l929) or human rhabdomyosarcoma (rd) cells displa ...201323760234
specific primer amplification of the vp1 region directed by 5' utr sequence analysis: enterovirus testing and identification in clinical samples from hand-foot-and-mouth disease patients.many genotypes of the enterovirus (ev) pathogens can cause clinical hand-foot-and-mouth disease (hfmd). therefore, rapid identification and monitoring of hfmd pathogens can be difficult, especially from the original clinical specimens. in this study, both universal pan-enterovirus and ev71/ca16 vp1-specific primer sets were designed and used to examine clinical specimens from hfmd patients. based on the initial sequence analysis of the 5'-untanslated region (5'-utr) and vp1 amplification product ...201323769858
hand, foot, mouth, brainstem, and heart disease resulting from enterovirus 71. 201323774351
rapid and highly sensitive detection of enterovirus 71 by using nanogold-enhanced electrochemical impedance spectroscopy.enterovirus 71 (ev71) infection is an emerging infectious disease causing neurological complications and/or death within two to three days after the development of fever and rash. a low viral titre in clinical specimens makes the detection of ev71 difficult. conventional approaches for detecting ev71 are time consuming, poorly sensitive, or complicated, and cannot be used effectively for clinical diagnosis. furthermore, ev71 and coxsackie virus a16 (ca16) may cross react in conventional assays. ...201323787733
characterization of enterovirus 71 and coxsackievirus a16 isolated in hand, foot, and mouth disease patients in guangdong, 2010.hand, foot, and mouth disease (hfmd) is an acute viral disease caused by human enteroviruses, especially human enterovirus 71 (hev71) and coxsackievirus a16 (cva16), and mainly affects infants and young children. after the outbreak in 2008 in fuyang, china, hfmd was classified as a category c notifiable infectious disease by the ministry of health of china.201323791223
differential gene expressions of the mapk signaling pathway in enterovirus 71-infected rhabdomyosarcoma cells.mitogen-activated protein kinase (mapk) signaling pathway plays an important role in response to viral infection. the aim of this study was to explore the function and mechanism of mapk signaling pathway in enterovirus 71 (ev71) infection of human rhabdomyosarcoma (rd) cells.201323797008
atypical hand-foot-mouth disease in children: a hospital-based prospective cohort study.in 2010, we observed children with atypical presentations of hand-foot-mouth disease (hfmd), such as rashes on earlobes and faces, or bullae on trunks and bilateral limbs. hyperpigmentation later developed as the bullous lesions crusted. thus, we intended to study the etiology of the illness and the phylogeny of the pathogens.201323800163
necrotizing myositis causes restrictive hypoventilation in a mouse model for human enterovirus 71 infection.enterovirus 71 (ev71) infections are associated with a high prevalence of hand, foot and mouth disease (hfmd) in children and occasionally cause lethal complications. most infections are self-limiting. however, resulting complications, including aseptic meningitis, encephalitis, poliomyelitis-like acute flaccid paralysis, and neurological pulmonary edema or hemorrhage, are responsible for the lethal symptoms of ev71 infection, the pathogenesis of which remain to be clarified.201323809248
genetic characterization of ev71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype d and recent emergence of a distinct lineage of subgenotype c2 in hong kong.enterovirus 71 (ev71) is a common etiological agent of hand, foot and mouth disease (hfmd) in children. ev71 epidemics have been reported in hong kong in recent years, and yet the genetic information of ev71 strains circulating in our locality is limited. the objective of this study was to investigate the genetic evolution of these ev71 isolates in hong kong over a 7-year period.201323822185
enterovirus infection among patients admitted to hospital in hong kong in 2010: epidemiology, clinical characteristics, and importance of molecular diagnosis.the activity of hand, foot, and mouth disease (hfmd) in hong kong was high in 2010. real-time reverse transcriptase-polymerase chain reaction (rt-pcr) had been performed routinely for diagnosis of enterovirus (ev) infection among hospitals in a geographical cluster. the aim of the study was to describe the epidemiology and the clinical pattern of ev-related hospital admission in 2010, and evaluate the impact of rt-pcr compared to conventional method. this was a retrospective study and patients w ...201323824683
what we are watching--five top global infectious disease threats, 2012: a perspective from cdc's global disease detection operations center.disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. the centers for disease control and prevention's (cdc) global disease detection (gdd) operations center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health th ...201323827387
validation-based insertional mutagenesis for identification of nup214 as a host factor for ev71 replication in rd cells.lentiviral validation-based insertional mutagenesis (vbim) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. using vbim, we conducted function-based genetic screening for host genes that affect enterovirus 71 (ev71) viral replication. this included host factors that are required for the life cycle of ev71 and host restriction factors that inhibit ev71 replication. several cell clones, resistant to ev71, were produced using ...201323831628
formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of h5n1/ev71/jev.combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (h5n1/h1n1), enterovirus 71 (ev71), and/or japanese encephalitis virus (jev) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. we demonstrated that the antigeni ...201323838466
first case of severe enterovirus 71 infection in portugal. 201323838666
comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.enterovirus 71 (ev71) infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (hfmd). this study aims to further characterize the specific immunological features in ev71-mediated hfmd patients presenting with differing degrees of disease severity.201323840697
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