Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
update on enterovirus 71 infection.human enterovirus type 71 (ev71) has emerged as a major cause of viral encephalitis in children worldwide. the identified ev71 receptors provide useful information for understanding ev71replication and tissue tropism. host factors interact with the internal ribosome entry site (ires) of ev71 to regulate viral translation. however, the specific molecular features of the ev71 genome that determine virulence remain unclear. the ev71 capsid protein vp1 region might contribute to virulence and neurot ...201424727707
estimation of contamination sources of human enteroviruses in a wastewater treatment and reclamation system by pcr-dgge.a polymerase chain reaction-denaturing gradient gel electrophoresis (pcr-dgge) method was employed to estimate the contamination sources of human enteroviruses and understand how their dominant strains vary in a wastewater treatment and reclamation system consisting of sewage collection, wastewater treatment with membrane bioreactor and open lakes for reclaimed water storage and reuse. after pcr-dgge using a selected primer set targeting enteroviruses, phylogenetic analysis of acquired enterovir ...201424715657
detection of enterovirus 71 gene from clinical specimens by reverse-transcription loop-mediated isothermal amplification.the objective of this study was to develop a sensitive, specific and rapid approach to diagnose hand foot and mouth disease (hfmd) for an early treatment by using loop-mediated isothermal amplification (lamp) technique.201424713896
[the exploration of the role of angiopoietin-2 in pulmonary edema induced by ev71 infection].to observe the clinic character of pulmonary edema (pe) induced by enterovirus 71 (ev71) and the change in angiopoietin-2 (ang-2), and to explore the correlation between ang-2 and pe.201424696919
[an investigation on a case of hand-foot-mouth disease caused by coxsackie-virus a6 associated with a vaccine-derived poliovirus co-infection].to identify the pathogen and characteristics on a case of hand-foot-mouth disease (hfmd) caused by coxsackie-virus a6 (ca6) associated with vaccine-derived poliovirus (vdpv) co-infection.201424685040
the multi-targeted kinase inhibitor sorafenib inhibits enterovirus 71 replication by regulating ires-dependent translation of viral proteins.the activation of erk and p38 signal cascade in host cells has been demonstrated to be essential for picornavirus enterovirus 71 (ev71) replication and up-regulation of virus-induced cyclooxygenase-2 (cox-2)/prostaglandins e2 (pge2) expression. the aim of this study was to examine the effects of sorafenib, a clinically approved anti-cancer multi-targeted kinase inhibitor, on the propagation and pathogenesis of ev71, with a view to its possible mechanism and potential use in the design of therapy ...201424680956
genetic polymorphism of ccl2-2510 and susceptibility to enterovirus 71 encephalitis in a chinese population.the study was performed in 36 chinese patients with enterovirus 71 (ev71) encephalitis and 141 patients with ev71-related hand, foot and mouth disease (hfmd) without encephalitis. genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism technique. patients with ev71 encephalitis had a significantly higher frequency of the ccl2-2510gg genotypes when compared to patients with ev71-related hfmd without encephalitis (66.7% vs. 41.8%, p=0.028). the frequency of cc ...201424788844
mutations in the non-structural protein region contribute to intra-genotypic evolution of enterovirus 71.clinical manifestations of enterovirus 71 (ev71) range from herpangina, hand-foot-and-mouth disease (hfmd), to severe neurological complications. unlike the situation of switching genotypes seen in ev71 outbreaks during 1998-2008 in taiwan, genotype b5 was responsible for two large outbreaks in 2008 and 2012, respectively. in china, by contrast, ev71 often persists as a single genotype in the population and causes frequent outbreaks. to investigate genetic changes in viral evolution, complete ev ...201424766641
in vitro and in vivo protection against enterovirus 71 by an antisense phosphorothioate oligonucleotide.enterovirus 71 (ev71) is a highly infectious virus that is a major cause of hand, foot, and mouth disease (hfmd), which can lead to severe neurological complications. currently, there is no effective therapy against ev71. five antisense oligodeoxynucleotides targeting the 5'-terminal conserved domain of the viral genome were designed using a method based on multiple predicted target mrna structures. they were then screened for anti-ev71 activity in vitro based on their ability to inhibit an ev71 ...201424756344
phenotypic and genotypic characteristics of novel mouse cell line (nih/3t3)-adapted human enterovirus 71 strains (ev71:tllm and ev71:tllmv).since its identification in 1969, enterovirus 71 (ev71) has been causing periodic outbreaks of infection in children worldwide and most prominently in the asia-pacific region. understanding the pathogenesis of enterovirus 71 (ev71) is hampered by the virus's inability to infect small animals and replicate in their derived in vitro cultured cells. this manuscript describes the phenotypic and genotypic characteristics of two selected ev71 strains (ev71:tllm and ev71:tllmv), which have been adapted ...201424671184
protection against lethal enterovirus 71 challenge in mice by a recombinant vaccine candidate containing a broadly cross-neutralizing epitope within the vp2 ef loop.human enterovirus 71 (ev71) is the main causative agent of hand, foot, and mouth disease (hfmd) and is associated with several severe neurological complications in the asia-pacific region. here, we evaluated that while passive transfer of neutralizing monoclonal antibody (nmab) against the vp2 protein protect against lethal ev71 infection in balb/c mice. protective nmab were mapped to residues 141-155 of vp2 by peptide elisa. high-resolution structural analysis showed that the epitope is part of ...201424669278
efficacy, safety, and immunogenicity of an enterovirus 71 vaccine in china.enterovirus 71 (ev71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease or herpangina worldwide. this phase 3 trial was designed to evaluate the efficacy, safety, and immunogenicity of an ev71 vaccine.201424571754
inhibition of mir-146a prevents enterovirus-induced death by restoring the production of type i interferon.there are no antivirals or vaccines available to treat enterovirus 71 (ev71) infections. although the type i interferon response, elicited upon virus infection, is critical to establishing host antiviral innate immunity, ev71 fails to induce this response efficiently. here we provide new insights into potential anti-ev71 therapy by showing that neutralization of ev71-induced mir-146a prevents death in mice by restarting the production of type i interferon. ev71 infection upregulates mir-146a, wh ...201424561744
attenuation of human enterovirus 71 high-replication-fidelity variants in ag129 mice.in a screen for ribavirin resistance, a novel high-fidelity variant of human enterovirus 71 (ev71) with the single amino acid change l123f in its rna-dependent rna polymerase (rdrp or 3d) was identified. based on the crystal structure of ev71 rdrp, l123 locates at the entrance of the rna template binding channel, which might form a fidelity checkpoint. ev71 rdrp-l123f variants generated less progeny in a guanidine resistance assay and virus populations with lower mutation frequencies in cell cul ...201424623423
a polymorphism in melanoma differentiation-associated gene 5 may be a risk factor for enterovirus 71 infection.enterovirus 71 (ev71) infection has a wide variety of clinical manifestations, from no symptoms to fatal disease. host immune response may be a determinant of disease severity. we investigated the association of polymorphisms in three pattern recognition receptor (prr) genes-toll-like receptor 3 (tlr3) (rs3775291), retinoic acid-inducible gene i (rig-i) (rs10813831) and melanoma differentiation-associated gene 5 (mda5) (rs1990760)-with the severity of ev71 infection. polymorphisms of candidate g ...201424621100
development of enterovirus 71 vaccines: from the lab bench to phase iii clinical trials.the widespread epidemics of enterovirus 71 (ev71) seriously affected the western pacific region. young children, especially those younger than 3 years are the most susceptible population to the ev71-associated diseases. several asian countries have begun to focus on the research and development of ev71 vaccines. five inactivated whole-virus ev71 candidate vaccines (three were manufactured in mainland china based on a c4 genotype strain, one in taiwan based on a b4 genotype strain and one in sing ...201424621093
the molecule of dc-sign captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection.enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease that occurs in young children. neither antiviral agents nor vaccines are available for efficiently combating viral infection. study of ev71-host interplay is important for understanding viral infection and developing strategies for prevention and therapy. here the interactions of ev71 with human dendritic cells were analyzed.201424620896
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
enterovirus 71 pathogenicity in monkeys and cotton rats.enterovirus 71 (ev71) is a neurovirulent non-polio enterovirus that can cause severe central nervous system (cns) infection in infants. vervet monkeys infected intracerebrally or intramuscularly with ev71 isolates from the bulgarian outbreak of 1975 developed clinical manifestations and pathological signs of encephalomyelitis and spinal poliomyelitis that were similar to ev71 neuroinfection in children. in addition, vervet monkeys with encephalomyelitis had severe alterations in the choroid plex ...201424158347
the population-based health effect of hand, foot and mouth disease in children in shanghai.an effective enterovirus 71 (ev71) vaccine is needed to control the annual outbreaks of hand, foot and mouth disease (hfmd) in china. adequate epidemiologic data relating to hfmd are needed to make decisions about appropriate public health interventions and implementation of the new ev71 vaccine.201424153009
clinico-radiological spectrum in enterovirus 71 infection involving the central nervous system in children.enterovirus 71 infection causes hand, foot and mouth disease in children, and can produce diverse neurologic complications. epidemics occurring in korea between 2009 and 2012 resulted in the death of some patients. the present study aimed to clarify the correlation between clinical features and mri findings in patients presenting with acute neurologic manifestations related to enterovirus 71 infection. based on their clinical features, the patients were classified into four clinical groups: (1) ...201424169271
epidemiology of enterovirus 71 infections in taiwan.enterovirus 71 (ev71) was first described in usa in 1969 but retrospective studies in the netherlands further detected ev71 in the clinical specimens collected in 1963. ev71 has one single serotype measured by using hyperimmune animal antisera but can be phylogenetically classified into three genogroups (a, b, and c) including 11 genotypes (a, b1-b5, c1-c5). in taiwan, ev71 caused a large-scale nationwide epidemic in 1998. retrospective studies further detected ev71 in clinical specimens collect ...201424120535
the enteroviruses: problems in need of treatments.specific antiviral therapy is currently not available for enterovirus (ev) infections. poliomyelitis, ev 71 neurologic disease, and neonatal ev disease are three manifestations of ev infections that exemplify the importance of developing antivirals for ev infections. despite tremendous strides in the effort to eradicate polio through vaccination, challenges remain, including the potential for transmission of neurovirulent vaccine-derived polioviruses which have genetically reverted from live-att ...201424119825
immunogenicity, safety, and immune persistence of a novel inactivated human enterovirus 71 vaccine: a phase ii, randomized, double-blind, placebo-controlled trial.vaccination is considered a top priority for the control of human enterovirus 71 (ev71) infection outbreaks.201423922377
development and evaluation of a real-time method of simultaneous amplification and testing of enterovirus 71 incorporating a rna internal control system.human enterovirus 71 (ev71) is a primary etiological agent of hand, foot, and mouth disease (hfmd). the associated infections have posed a serious threat to the public health. in the present study, a real-time simultaneous amplification and testing (sat) technology was developed for detecting ev71 (sat-ev71). the rna of ev71 and an internal control (ic) were amplified and analyzed simultaneously by isothermal amplification and real-time detection of fluorescence using routine real-time pcr. furt ...201424269796
a 3c(pro)-dependent bioluminescence imaging assay for in vivo evaluation of anti-enterovirus 71 agents.enterovirus 71 (ev71), a member of picornaviridae, is one of the major pathogens of human hand, foot and mouth disease. ev71 mainly infects children and causes severe neurological complications and even death. the pathogenesis of ev71 infection is largely unknown, and no clinically approved vaccine or effective treatment is available to date. here we described a novel bioluminescence imaging approach for ev71 detection. in this approach, a plasmid-based reporter was constructed to express the fu ...201424263113
recent developments in antiviral agents against enterovirus 71 infection.enterovirus 71 (ev-71) is the main etiological agent of hand, foot and mouth disease (hfmd). recent ev-71 outbreaks in asia-pacific were not limited to mild hfmd, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. the absence of licensed therapeutics for clinical use has intensified research into anti-ev-71 development. this review highlights the potential antiviral agents targetin ...201424521134
construction and characterization of a recombinant human adenovirus type 3 vector containing two foreign neutralizing epitopes in hexon.the "antigen capsid-incorporation" strategy has been developed for adenovirus-based vaccines in the context of several diseases. exogenous antigenic peptides incorporated into the adenovirus capsid structure can induce a robust and boosted antigen-specific immune response. recently, we sought to generate a multivalent adenovirus type 3 (ad3) vaccine vector by incorporating multiple epitopes into the major adenovirus capsid protein, hexon. in the present study, a multivalent recombinant ad3 vacci ...201424518297
the nuclear protein sam68 is redistributed to the cytoplasm and is involved in pi3k/akt activation during ev71 infection.nuclear proteins can be triggered to be redistributed to the cytoplasm to assist with ev71 virus replication. this process is frequently involved in cellular signal transduction upon virus infection. in this study, we have demonstrated that a new nuclear protein, 68-kda src-associated in mitosis protein (sam68), was translocated to the cytoplasm and was co-localized with ev71 during virus infection. confocal microscopy and subcellular fractionation assay confirmed that virus 3c protease triggere ...201424316008
peripheral t lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease.inflammatory mediators (i.e. cytokines) play a pivotal role in the regulation of pathophysiological processes during ev71-induced hand, foot and mouth disease (hfmd). different t cell subsets have distinct cytokine secretion profiles, and alteration in the t cell subsets frequency (imbalance) during infection leads to changed cytokine patterns. however, the effects of ev71 infection on t cell subsets were not clear. the objective of this study was to determine whether ev71-induced hfmd can be ex ...201424316007
construction of an infectious cdna clone of enterovirus 71: insights into the factors ensuring experimental success.enterovirus 71 (ev 71) is a causative agent of mild hand foot and mouth disease but is capable of causing severe complications in the cns in young children. reverse genetics technology is currently widely used to study the pathogenesis of the virus. the aim of this work was to determine and evaluate the factors which can contribute to infectivity of ev 71 rna transcripts in vitro. two strategies, overlapping rt-pcr and long distance rt-pcr, were employed to obtain the full-length genome cdna clo ...201424361875
the mechanism of translation initiation on type 1 picornavirus iress.picornavirus type 1 iress comprise five principal domains (dii-dvi). whereas dv binds eif4g, a conserved aug in dvi was suggested to stimulate attachment of 43s ribosomal preinitiation complexes, which then scan to the initiation codon. initiation on type 1 iress also requires ires trans-acting factors (itafs), and several candidates have been proposed. here, we report the in vitro reconstitution of initiation on three type 1 iress: poliovirus (pv), enterovirus 71 (ev71), and bovine enterovirus ...201424357634
suramin inhibits ev71 infection.enterovirus-71 (ev71) is one of the major causative reagents for hand-foot-and-mouth disease. in particular, ev71 causes severe central nervous system infections and leads to numerous dead cases. although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. in the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit ev71 p ...201424374150
effect of all-trans-retinoic acid on enterovirus 71 infection in vitro.our previous studies have shown that vitamin a (va) status is associated with antiviral immunity and pathogenic conditions in enterovirus 71 (ev71)-infected children. in the present study, we established an in vitro model to investigate the effects and potential mechanism of the antiviral activity of va. human monocytic u937 cells were cultured in vitro and infected with ev71. all-trans-retinoic acid (atra), the active metabolite of va, and ro 41-5253, a retinoic acid receptor-α (rar-α) antagoni ...201424495389
polyc-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 rna in membrane-associated complex to facilitate viral replication.enterovirus 71 (ev71) is one causative agent of hand, foot, and mouth disease (hfmd), which may lead to severe neurological disorders and mortality in children. ev71 genome is a positive single-stranded rna containing a single open reading frame (orf) flanked by 5'-untranslated region (5'utr) and 3'utr. the 5'utr is fundamentally important for virus replication by interacting with cellular proteins. here, we revealed that poly(c)-binding protein 1 (pcbp1) specifically binds to the 5'utr of ev71. ...201424489926
hand, foot, and mouth disease in china, 2008-12: an epidemiological study.hand, foot, and mouth disease is a common childhood illness caused by enteroviruses. increasingly, the disease has a substantial burden throughout east and southeast asia. to better inform vaccine and other interventions, we characterised the epidemiology of hand, foot, and mouth disease in china on the basis of enhanced surveillance.201424485991
neutralizing antibodies can initiate genome release from human enterovirus 71.antibodies were prepared by immunizing mice with empty, immature particles of human enterovirus 71 (ev71), a picornavirus that causes severe neurological disease in young children. the capsid structure of these empty particles is different from that of the mature virus and is similar to "a" particles encountered when picornaviruses recognize a potential host cell before genome release. the monoclonal antibody e18, generated by this immunization, induced a conformational change when incubated at ...201424469789
enterovirus 71 infection-associated acute flaccid paralysis: a case series of long-term neurologic follow-up.the authors undertook long-term neurologic outcomes of 27 patients aged 0 to 15 years with enterovirus 71-related acute flaccid paralysis from june 1998 to july 2012. motor function outcome was graded from class i (complete recovery) to class v (permanent paralytic limbs). twelve of 20 patients (60%) who received intravenous immunoglobulin for treatment of acute flaccid paralysis had motor function outcomes in classes iii to v. the median duration of follow-up was 6 months, during which time 7 o ...201424453152
a novel finding for enterovirus virulence from the capsid protein vp1 of ev71 circulating in mainland china.enterovirus 71 (ev71) is a neurotropic virus that causes various clinical manifestations in young children, ranging from asymptomatic to fatal. different pathotypes of ev71 notably differ in virulence. several virulence determinants of ev71 have been predicted. however, these reported virulence determinants could not be used to identify the ev71 strains of subgenotype c4, which mainly circulate in china. in this study, vp1 sequences of 37 ev71 strains from severe cases (sc-ev71) and 192 ev71 str ...201424442718
interleukin-8 is elevated in severe hand, foot, and mouth disease.enterovirus 71 (ev71) infections can cause hand, foot, and mouth disease (hfmd), which is a potentially fatal illness in children. epidemics of hfmd are seen every year globally and present an increasing threat to public health worldwide.201424423718
spatio-temporal analysis on enterovirus cases through integrated surveillance in taiwan.severe epidemics of enterovirus have occurred frequently in malaysia, singapore, taiwan, cambodia, and china, involving cases of pulmonary edema, hemorrhage and encephalitis, and an effective vaccine has not been available. the specific aim of this study was to understand the epidemiological characteristics of mild and severe enterovirus cases through integrated surveillance data.201424400725
the gene expression profile of peripheral blood mononuclear cells from ev71-infected rhesus infants and the significance in viral pathogenesis.enterovirus 71 (ev71) is the major pathogen responsible for fatal hand, foot and mouth disease (hfmd). our previous work reported on an ev71-infected rhesus monkey infant model that presented with histo-pathologic changes of the central nervous system (cns) and lungs. this study is focused on the correlated modulation of gene expression in the peripheral blood mononuclear cells (pbmcs) from ev71-infected rhesus monkey infants. the expression of more than 500 functional genes associated with mult ...201424392094
the approved pediatric drug suramin identified as a clinical candidate for the treatment of ev71 infection-suramin inhibits ev71 infection in vitro and in vivo.enterovirus 71 (ev71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. there is an urgent unmet medical need for new pharmaceutical agents to control ev71 infections. using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked ev71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. moreover, we de ...201426038755
a neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses.vaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain bj110, which has a c4 genotype. porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. oral and combined oral-nasal infection of 5-day-old neonatal gnotobiotic pigs with 5×10( ...201426038741
neutralizing antibody responses to enterovirus and adenovirus in healthy adults in china.hand, foot and mouth disease (hfmd) is an important public health problem that has emerged over the past several years. hfmd predominantly infects children under seven years old and occasionally causes severe disease in adults. among the enteroviruses, enterovirus 71 (ev71) and coxsackievirus 16 (ca16) are the major causative agents of hfmd. in addition, adenovirus cocirculates with enterovirus and has become a possible additional pathogenic factor for hfmd in some cases. here, we have investiga ...201426038738
receptors for enterovirus 71.enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease (hfmd). occasionally, ev71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. several molecules act as cell surface receptors that stimulate ev71 infection, including scavenger receptor b2 (scarb2), p-selectin glycoprotein ligand-1 (psgl-1), sialylated glycan, heparan sulfate and annexin ii (anx2). scarb2 plays critica ...201426038749
[hand-foot-mouth disease pathogen separation and ev71 vp1 gene analysis in sanmenxia city, henan province, china].the aim of this study was to understand the enterovirus types and biological features of pediatric cases of hfmd in sanmenxia city during 2011, and compare the latter to a cohort of healthy children. stool samples of 55 cases of hfmd and 60 healthy children were collected for the isolation and identification of enteroviruses using rna extraction and real-time rt-pcr assays. ev71 and ca16 were identified by nucleotide sequencing using virus-specific vp1 primers; for the other enteroviruses, 012/0 ...201425868277
analysis of synonymous codon usage in enterovirus 71.enterovirus 71 (ev71) is the major cause of hand-foot-and-mouth disease in children. in our study, using the complete genome sequences of 42 ev71 representing all three genotypes, we analyzed synonymous codon usage and the relative dinucleotide abundance in ev71 genome. the general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in ev71 genome. furthermore, we observe ...201425674591
[heat effect stability of inactivated enterovirus 71 vaccine].to investigate the effect of temperature on the stability of intermediate and final products of inactivated enterovirus 71 vaccine, which was prepared in human diploid cells.201425388471
enterovirus 71 infects brain-derived neural progenitor cells.neural progenitor cells (npcs) are stem cells that can differentiate into various neural lineage cells. the damage and loss of npcs are associated with neurological conditions such as cognitive deficits and memory impairment. in a long-term study of patients with ev71, cognitive disorders were observed. therefore, we hypothesized that npcs may be permissive to ev71 infection. we demonstrated that npcs are prone to ev71 infection and that these stem cells can support the active replication of thi ...201425299565
[effects of ph on the properties of colloidal gold labeling monoclonal antibody].to investigate the influence of ph on the properties of colloidal gold labeling monoclonal antibody (mab).201425374082
il-6, il-10 and il-13 are associated with pathogenesis in children with enterovirus 71 infection.in the present study, the aim was to reveal the relationship of serum il-6, il-10 and il-13 levels in patient with enterovirus 71 (ev71) infection. to elucidate the role of immune mechanisms in the pathogenesis of hand, foot, and mouth disease (hfmd), we analyzed the cytokine of 112 ev71-infected patients. a significant elevation of serum (interleukin) il-6, il-10 and il-13 levels in patients with ev71 infection compare with un-ev71 infection hfmd patient and healthy individuals. the production ...201425356130
mri characteristics and follow-up findings in patients with neurological complications of enterovirus 71-related hand, foot, and mouth disease.this study aimed to investigate the magnetic resonance imaging (mri) characteristics and clinical and mri follow-up findings of patients with neurological complications of enterovirus 71-related hand, foot and mouth disease.201425356127
the causes and consequences of childhood encephalitis in asia.encephalitis is caused by inflammation and/or infection of the brain. it is a important condition in asian children in whom it is most frequently caused by japanese encephalitis virus, associated with a considerable burden of disease. other common causes in asia include: enteroviruses (especially enterovirus 71), dengue, influenza, the herpesviruses, measles, mumps and rubella viruses. rabies continues to result in high mortality mostly in asian children, which represents missed opportunities fo ...201425336078
apigenin inhibits enterovirus-71 infection by disrupting viral rna association with trans-acting factors.flavonoids are widely distributed natural products with broad biological activities. apigenin is a dietary flavonoid that has recently been demonstrated to interact with heterogeneous nuclear ribonucleoproteins (hnrnps) and interferes with their rna editing activity. we investigated whether apigenin possessed antiviral activity against enterovirus-71 (ev71) infection since ev71 infection requires of hnrnp proteins. we found that apigenin selectively blocks ev71 infection by disrupting viral rna ...201425330384
is over-reporting a problem in mandatory communicable disease reporting? the taiwanese experience on enterovirus 71.in taiwan, severe enteroviral infections must be reported to the government within 24 hours to ensure that severe enterovirus 71 (ev71) infections can be detected early. the objective of this research was to ascertain whether over-reporting is a problem in mandatory disease-reporting systems.201425313606
detection of hand, foot and mouth disease in the yucatan peninsula of mexico.we report a case of hand, foot and mouth disease (hfmd) in a 5-year-old male from merida city in the yucatan peninsula of mexico. a clinical and physical examination revealed that the patient had symptoms typical of hfmd, including fever, fatigue, odynophagia, throat edema, hyperemia, lesions on the hands and feet, and blisters in the oral cavity. the patient fully recovered after a convalescence period of almost three weeks. reverse transcription-polymerase chain reaction and nucleotide sequenc ...201425568757
[research methods in protein-protein and protein-nucleic acid interactions and application in the study of human enterovirus a71].methods for analyses of protein-protein interactions include: yeast two hybrid (y2h), phage dis- play (pd), co-immunoprecipitation (co-ip), glutathione s-transferase pull-down (gst pull-down), cellular co-localization, far-western blotting, virus overlay protein binding assay (vopba), surface plasmon resonance (spr), and fluorescence resonance energy transfer (fret). technologies for the detection of protein-nucleic acid interactions include: yeast one hybrid (y1h), chromatin immunoprecipitation ...201425562971
mek/erk signaling pathway is required for enterovirus 71 replication in immature dendritic cells.the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (mek/erk) signaling pathway is involved in viral life cycle. however, the effect of mek/erk pathway in enterovirus 71(ev71)-infected immature dendritic cells (idcs) is still unclear.201425548009
bpr-3p0128 inhibits rna-dependent rna polymerase elongation and vpg uridylylation activities of enterovirus 71.enterovirus 71 (ev71) infections can cause hand, foot, and mouth disease with severe neurological complications. because no clinical drug is available for treating ev71 infections, developing an efficient antiviral medication against ev71 infection is crucial. this study indicated that 6-bromo-2-[1-(2,5-dimethylphenyl)-5-methyl-1h-pyrazol-4-yl] quinoline-4-carboxylic acid (bpr-3p0128) exhibits excellent antiviral activity against ev71 (ec50 = 0.0029 μm). bpr-3p0128 inhibits viral replication dur ...201425448086
an adenosine nucleoside analogue nitd008 inhibits ev71 proliferation.enterovirus 71 (ev71), one of the major causative agents of hand-foot-mouth disease (hfmd), causes severe pandemics and hundreds of deaths in the asia-pacific region annually and is an enormous public health threat. however, effective therapeutic antiviral drugs against ev71 are rare. nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. we evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue nit ...201425446894
folding fan mode counter-current chromatography offers fast blind screening for drug discovery. case study: finding anti-enterovirus 71 agents from anemarrhena asphodeloides.a new application of counter-current chromatography (ccc) in drug discovery, called folding fan mode (ffm), is designed to eliminate the extensive and time-consuming calculation of the partition coefficients of some preset compounds in conventional ccc separation. careful reading of reports in the literature reveals that, when two-phase solvent systems are listed in a polarity-increasing sequence, the isolates also show a similar trend in polarity. the relationship between the two-phase solvent ...201425441347
activation of pi3k/akt pathway limits jnk-mediated apoptosis during ev71 infection.apoptosis is frequently induced to inhibit virus replication during infection of enterovirus 71 (ev71). on the contrary, anti-apoptotic pathway, such as pi3k/akt pathway, is simultaneously exploited by ev71 to accomplish the viral life cycle. the relationship by which ev71-induced apoptosis and pi3k/akt signaling pathway remains to be elucidated. in this study, we demonstrated that ev71 infection altered bax conformation and triggered its redistribution from the cytosol to mitochondria in rd cel ...201425116390
mir-27a suppresses ev71 replication by directly targeting egfr.enterovirus 71 (ev71), a major causative agent of hand, foot, and mouth disease, has broken out several times and was accompanied by neurological disease. micrornas, a class of small non-coding rnas that are approximately 20 nucleotides long, play important roles in the regulation of various biological processes, including antiviral defense. however, the roles of mirnas in ev71 replication and pathogenesis are not well understood. in this study, we found that the expression of mir-27a was signif ...201425212431
[mir373 and mir542-5p regulate the replication of enterovirus 71 in rhabdomyosarcoma cells].micrornas (mirnas) play an important role in infection and replication of virus in host cells. to identify cellular mirnas involved in the host response to enterovirus 71 (ev71) infection, we examined mirnas effects on the replication of ev71 in rhabdomyosarcoma cells. we constructed target gene of mirnas screening system. 3'untranslated region (utr) dual luciferase reporter analysis was used to identify putative mirna targets in the ev71 virus genome. first, 13 segments of ev71 virus genomes we ...201425212011
inhibition of enterovirus 71 by adenosine analog nitd008.enterovirus 71 (ev71) is a major viral pathogen in china and southeast asia. there is no clinically approved vaccine or antiviral therapy for ev71 infection. nitd008, an adenosine analog, is an inhibitor of flavivirus that blocks viral rna synthesis. here we report that nitd008 has potent antiviral activity against ev71. in cell culture, the compound inhibits ev71 at a 50% effective concentration of 0.67 μm and a 50% cytotoxic concentration of 119.97 μm. when administered at 5 mg/kg in an ev71 m ...201425100827
clinical features of severe cases of hand, foot and mouth disease with ev71 virus infection in china.hand, foot and mouth disease (hfmd) caused by ev71 infection has become one of the major public health issues in china, which deeply affects children's health. the prevention and control of ev71 is a challenge currently because there is no safe and effective vaccine or antiviral medications available.201425097582
[study on adjuvant effect of oral recombinant subunit vaccine formulated with chitosan against human enterovirus 71].to evaluate the adjuvant effect of recombinant enterovirus 71 (ev71) subunit vaccine formulated with chitosan, rabbits were orally immunized with recombinant vp1 (rvp1) or rvp1 mixed with chitosan adjuvant. levels of virus-specific igg and iga antibodies in sera, mucosal wash buffer (intestine, nasal cavity, and lung), and feces were determined by indirect enzyme-linked immunosorbent assay (elisa). the titers of neutralizing antibodies against ev71 were determined using cytopathic effect-based n ...201425118374
the identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3ab.human enterovirus 71 (ev71) belongs to the genus enterovirus in the family picornaviridae and has been recognized as one of the most important pathogens that cause emerging infectious disease. despite of the importance of ev71, the nonstructural protein 3ab from this virus is little understood for its function during ev71 replication. here we expressed ev71 3ab protein as recombinant protein in a eukaryotic expression system and uncovered that this protein possesses a nucleic acid helix-destabil ...201425113906
early dexamethasone treatment exacerbates enterovirus 71 infection in mice.enterovirus 71 (ev71) infection can induce encephalitis. overt immune responses is suspected to cause severe symptoms, so anti-inflammatory agents, corticosteroids have been recommended for treatment. however, one clinical study reported that treatment with glucocorticoids, dexamethasone (dex) exacerbates disease severity. here we investigated dex treatment on ev71 infection using the murine model and found that both long-term (14-day) and short-term (4-day) dex treatment starting from 1 or 3 da ...201425104614
the cellular receptor for enterovirus 71. 201425103897
human diploid mrc-5 cells exhibit several critical properties of human umbilical cord-derived mesenchymal stem cells.mrc-5 is the most common human diploid cell line used in production of viral vaccines; mesenchymal stem cells (mscs) is a type of adult multipotent stem cells. both cell types share the same fibroblast-like morphology and maintain a normal diploid karyotype over long in vitro expansion. however, other than these similarities, very little is known about mrc-5 in terms of biological properties possessed by mscs. in this study, we compared mrc-5 with human umbilical cord-derived mscs (huc-mscs), wh ...201425086263
inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives.a large number of bioactive pentacyclic triterpenoids have been shown to have multiple biological activities. this study was conducted to evaluate the inhibitory activities of 6 newly synthesized and novel pentacyclic triterpenoids against enterovirus 71 (ev71). the parent compound, ursolic acid (ua), showed the greatest inhibitory activity against ev71, while oleanolic acid (oa), asiatic acid (aa), and synthetic derivatives of 18-β-glycyrrhetinic acid (ga) and oa also exhibited inhibitory effec ...201425087628
delivery of human ev71 receptors by adeno-associated virus increases ev71 infection-induced local inflammation in adult mice.enterovirus71 (ev71) is now recognized as an emerging neurotropic virus in asia and one major causative agent of hand-foot-mouth diseases (hfmd). however potential animal models for vaccine development are limited to young mice. in this study, we used an adeno-associated virus (aav) vector to introduce the human ev71 receptors p-selectin glycoprotein ligand-1 (hpsgl1) or a scavenger receptor class-b member-2 (hscarb2) into adult icr mice to change their susceptibility to ev71 infection. mice wer ...201425243194
comparison of the detection rates of rt-pcr and virus culture using a combination of specimens from multiple sites for enterovirus-associated encephalomyelitis during enterovirus 71 epidemic.enterovirus (ev) 71 may cause severe neurological illness in the pediatric population. the present study aimed to compare the detection rates of reverse transcription-polymerase chain reaction (rt-pcr) with pan-ev/ev71 type- specific primers and virus culture (vc) for the identification of ev and ev71 using specimens from multiple sites. in total, specimens from throat/rectal swabs, cerebrospinal fluid (csf), and blood from 66 patients diagnosed with ev encephalomyelitis were subjected to both r ...201425241681
[protective effect of an angiotensin-converting-enzyme inhibitor on neurogenic pulmonary edema in rabbits].neurogenic pulmonary edema (npe ) was indicative of poor prognosis in the epidemic of enterovirus 71 infections. the pathogenesis of npe remains poorly understood. the objectives of this experimental study were to explore whether ras is activated during npe in rabbit models induced by fibrin and the effects of an angiotensin converting enzyme inhibitor (enalaprilat) on npe.201425224238
[discussion on the vaccination strategy of enterovirus type 71 vaccine]. 201425219429
the limp-2/scarb2 binding motif on acid β-glucosidase: basic and applied implications for gaucher disease and associated neurodegenerative diseases.the acid β-glucosidase (glucocerbrosidase (gcase)) binding sequence to limp-2 (lysosomal integral membrane protein 2), the receptor for intracellular gcase trafficking to the lysosome, has been identified. heterologous expression of deletion constructs, the available gcase crystal structures, and binding and co-localization of identified peptides or mutant gcases were used to identify and characterize a highly conserved 11-amino acid sequence, dspiivditkd, within human gcase. the binding to limp ...201425202012
the capsid binder vapendavir and the novel protease inhibitor sg85 inhibit enterovirus 71 replication.antivirals against enterovirus 71 (ev71) are urgently needed. we demonstrate that the novel enteroviral protease inhibitor (pi) sg85 and capsid binder (cb) vapendavir efficiently inhibit the in vitro replication of 21 ev71 strains/isolates that are representative of the different genogroups a, b, and c. the pi rupintrivir, the cb pirodavir, and the host-targeting compound enviroxime, which were included as reference compounds, also inhibited the replication of all isolates. remarkably, the cb co ...201425199773
pathological examinations of an enterovirus 71 infection: an autopsy case.we report an 8-month-old female infant with the fatal enterovirus 71 infection here. clinically, she developed respiratory failure and severe pulmonary edema rapidly. histologically, the lung specimen showed diffuse, severe pulmonary congestion and edema with focal intra-alveolar hemorrhage and typical features of acute encephalitis were easily identified under light microscope. immunohistochemically, enterovirus 71 antigen was positive in the cerebella and brainstem. we measured the viral loads ...201425197403
the combination effects of licl and the active leflunomide metabolite, a771726, on viral-induced interleukin 6 production and ev-a71 replication.enterovirus 71 (ev-a71) is a neurotropic virus that can cause severe complications involving the central nervous system. no effective antiviral therapeutics are available for treating ev-a71 infection and drug discovery efforts are rarely focused to target this disease. thus, the main goal of this study was to discover existing drugs with novel indications that may effectively inhibit ev-a71 replication and the inflammatory cytokines elevation. in this study, we showed that licl, a gsk3β inhibit ...201425412347
antiviral effects against ev71 of pimprinine and its derivatives isolated from streptomyces sp.the pimprinine family of compounds represent very important and promising microbial metabolites for drug discovery. however, their ability in inhibiting viral infections has not yet been tested.201425410379
an outbreak of enterovirus 71 in metropolitan sydney: enhanced surveillance and lessons learnt.to report the findings of the enhanced surveillance set up in new south wales in response to the recent outbreak of human enterovirus 71 (ev71) infection.201425495312
[enterotoxigenic escherichia coli heat-labile enterotoxin b subunit can efficiently induce and enhance the mucosal immune response to enterovirus 71].to detect the immunogenicity of enterotoxigenic escherichia coli heat-labile enterotoxin b subunit (ltb) and evaluate the immune effect of enterovirus 71 (ev71) capsid protein vp1 together with ltb by the intranasal route.201425481175
characterization of the enterovirus 71 p1 polyprotein expressed in pichia pastor as a candidate vaccine.human enterovirus 71 (ev71) plays an important role in hand, foot, and mouth disease (hfmd), which recently caused the death of hundreds of children in the asia-pacific region. however, there are no specific treatments available for ev71 infections; thus, a safe and effective vaccine is needed urgently. in this study, we developed an effective and economical method for producing ev71 polyprotein (p1 protein) in pichia pastoris. furthermore, we evaluated the potential of p1 protein as a candidate ...201425424925
enterovirus 71 can directly infect the brainstem via cranial nerves and infection can be ameliorated by passive immunization.enterovirus 71 (ev71)-associated hand, foot, and mouth disease may be complicated by encephalomyelitis. we investigated ev71 brainstem infection and whether this infection could be ameliorated by passive immunization in a mouse model. enterovirus 71 was injected into unilateral jaw/facial muscles of 2-week-old mice, and hyperimmune sera were given before or after infection. harvested tissues were studied by light microscopy, immunohistochemistry, in situ hybridization, and viral titration. in un ...201425289894
a neonate with hand, foot, and mouth disease complicated with brainstem encephalitis and pulmonary edema:a complete recovery.hand, foot, and mouth disease (hfmd) with serious complications and fatal cases have been reported over the last decade worldwide. the authors report a rare case of hfmd in a neonate complicated with brainstem encephalitis and pulmonary edema. she had fever, lethargy, dyspnea. physical examination revealed shock signs, fine rales on both lungs, absent moro reflex. the patient had a rapidly progressive course with seizures, coma, no spontaneous breathing, chemosis. there were some vesicles on lef ...201425097545
cyclophilin a associates with enterovirus-71 virus capsid and plays an essential role in viral infection as an uncoating regulator.viruses utilize host factors for their efficient proliferation. by evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin a (cypa), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate ev71 proliferation. we demonstrated that cypa played an essential role in ev71 entry and that the rna interference-mediated reduction of endogenous cypa expression led to decreased ev71 multiplication. we further rev ...201425275585
[effects of ribavirin aerosol on viral exclusion of patients with hand-foot-mouth disease].to explore the roles of ribavirin aerosol in the prevention and treatment of hand-foot-mouth disease (hfmd).201425146745
immunodeficient mouse models with different disease profiles by in vivo infection with the same clinical isolate of enterovirus 71.like poliovirus infection, severe infection with enterovirus 71 (ev71) can cause neuropathology. unlike poliovirus, ev71 is often associated with hand-foot-and-mouth disease (hfmd). here we established three mouse models for experimental infection with the same clinical isolate of ev71. the nod/scid mouse model is unique for the development of skin rash, an hfmd-like symptom. while the nod/scid mice developed limb paralysis and death at near-100% efficiency, the gamma interferon receptor knockou ...201425142603
enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model.we previously reported that enterovirus 71 (ev71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. in the present study we further investigated whether ev71 infection of neuronal sk-n-sh cells induces an autophagic flux. furthermore, the effects of autophagy on ev71-related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted ev71 (mp4 strain) into 6-day-old icr suckling mice.201425139436
the clinical correlation of regulatory t cells and cyclic adenosine monophosphate in enterovirus 71 infection.brainstem encephalitis (be) and pulmonary edema (pe) are notable complications of enterovirus 71 (ev71) infection.201425010330
deferoxamine compensates for decreases in b cell counts and reduces mortality in enterovirus 71-infected mice.enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. no vaccine or antiviral therapy is currently available. in this work, we found that the number of b cells was reduced in enterovirus 71-infected mice. deferoxamine, a marine microbial natural product, compensated for the decreased levels of b cells caused by enterovirus 71 infection. the neutralizing antibody titer was also improved after deferoxamine treatment. furthermore, de ...201425003792
the correlation between the presence of viremia and clinical severity in patients with enterovirus 71 infection: a multi-center cohort study.enterovirus 71 (ev71) is a great disease burden across the whole world, particularly in southeast asia. however, in recent decades, the pathogenesis of severe ev71 infection was not well understood. this study was aimed to investigate the correlation between the presence of viremia and the clinical severity of ev71 infection.201425069383
new introductions of enterovirus 71 subgenogroup c4 strains, france, 2012.in france during 2012, human enterovirus 71 (ev-a71) subgenogroup c4 strains were detected in 4 children hospitalized for neonatal fever or meningitis. phylogenetic analysis showed novel and independent ev-a71 introductions, presumably from china, and suggested circulation of c4 strains throughout france. this observation emphasizes the need for monitoring ev-a71 infections in europe.201425061698
monitoring antigenic variations of enterovirus 71: implications for virus surveillance and vaccine development.enterovirus 71 (ev71) causes life-threatening epidemics in asia and can be phylogenetically classified into three major genogroups (a ∼ c) including 11 genotypes (a, b1 ∼ b5, and c1 ∼ c5). recently, ev71 epidemics occurred cyclically in taiwan with different genotypes. in recent years, human studies using post-infection sera obtained from children have detected antigenic variations among different ev71 strains. therefore, surveillance of enterovirus 71 should include phylogenetic and antigenic a ...201425058733
solution structure of the 2a protease from a common cold agent, human rhinovirus c2, strain w12.human rhinovirus strains differ greatly in their virulence, and this has been correlated with the differing substrate specificity of the respective 2a protease (2apro). rhinoviruses use their 2apro to cleave a spectrum of cellular proteins important to virus replication and anti-host activities. these enzymes share a chymotrypsin-like fold stabilized by a tetra-coordinated zinc ion. the catalytic triad consists of conserved cys (c105), his (h34), and asp (d18) residues. we used a semi-automated ...201424937088
a novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of vp3 protein.hand, foot and mouth disease caused by enterovirus 71(ev71) leads to the majority of neurological complications and death in young children. while putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. ideally, ev71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. to date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of vp1 has been identified. ...201424875055
toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.enterovirus 71 (ev71), a positive-stranded rna virus, is the major cause of hand, foot, and mouth disease (hfmd) with severe neurological symptoms. antiviral type i interferon (alpha/beta interferon [ifn-α/β]) responses initiated from innate receptor signaling are inhibited by ev71-encoded proteases. it is less well understood whether ev71-induced apoptosis provides a signal to activate type i interferon responses as a host defensive mechanism. in this report, we found that ev71 alone cannot act ...201425078697
distribution of ev71 receptors scarb2 and psgl-1 in human tissues.the aim of this study was to investigate the distribution of enterovirus 71 (ev71) receptors scarb2 and psgl-1 in human tissues. the samples were chosen from archived specimens, and the profiles of two receptors were detected in the gastrointestinal tract, lung, and brain in situ by immunohistochemistry. scarb2 was detected in all the tissues studied, and strong staining was observed in the gastric fundus gland, mucosal and glandular epithelia of the intestine. similar expression was found in br ...201424997419
Displaying items 1201 - 1300 of 1831