| environmental alkylphenols modulate cytokine expression in plasmacytoid dendritic cells. | alkylphenols, such as nonylphenol (np) and 4-octylphenol (4-op), have the potential to disturb immune system due to their weak estrogen-like activity, an effect with potential serious public health impact due to the worldwide distribution of these substances. plasmacytoid dendritic cells (pdcs) can secrete large amounts of type i ifns and are critical in immune regulation. however, there has been limited study about the influence of alkylphenols on the function of pdcs. | 2013 | 24039973 |
| [relationship between g6pd deficiency and hand-foot-mouth disease induced by enterovirus 71]. | to study the influence of glucose-6-phosphate dehydrogenase (g6pd) deficiency on hand-foot-mouth disease (hfmd) induced by enterovirus 71 (ev71) , and possible mechanisms. | 2013 | 24034918 |
| [cloning, expression and activity determination of capsid protein vp1 of enterovirus type 71]. | | 2013 | 24027809 |
| crystal structure of 2a proteinase from hand, foot and mouth disease virus. | ev71 is responsible for several epidemics worldwide; however, the effective antiviral drug is unavailable to date. the 2a proteinase (2a(pro)) of ev71 presents a promising drug target due to its multiple roles in virus replication, inhibition of host protein synthesis and evasion of innate immunity. we determined the crystal structure of ev71 2a(pro) at 1.85å resolution, revealing that the proteinase maintains a chymotrypsin-like fold. the active site is composed of the catalytic triads c110a, h ... | 2013 | 23973886 |
| proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71. | to clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (hfmd) infected by enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe hfmd children and 5 healthy children. | 2013 | 23961958 |
| transgenic mouse model for the study of enterovirus 71 neuropathogenesis. | enterovirus 71 (ev71) typically causes mild hand-foot-and-mouth disease in children, but it can also cause severe neurological disease. recently, epidemic outbreaks of ev71 with significant mortality have been reported in the asia-pacific region, and ev71 infection has become a serious public health concern worldwide. however, there is little information available concerning ev71 neuropathogenesis, and no vaccines or anti-ev71 drugs have been developed. previous studies of this disease have used ... | 2013 | 23959904 |
| soluble interleukin-6 receptor-mediated innate immune response to dna and rna viruses. | the interleukin-6 (il-6) receptor, which exists as membrane-bound and soluble forms, plays critical roles in the immune response. the soluble il-6 receptor (sil6r) has been identified as a potential therapeutic target for preventing coronary heart disease. however, little is known about the role of this receptor during viral infection. in this study, we show that sil6r, but not il-6, is induced by viral infection via the cyclooxygenase-2 pathway. interestingly, sil6r, but not il-6, exhibited ext ... | 2013 | 23946454 |
| [epidemiological and etiological characteristics of hand-foot-mouth disease in ningbo, zhejiang province, 2008-2011]. | to analyze the epidemiological characteristics of hand foot and mouth disease (hfmd) in ningbo. | 2013 | 23937841 |
| enterovirus 71 binding to psgl-1 on leukocytes: vp1-145 acts as a molecular switch to control receptor interaction. | some strains of enterovirus 71 (ev71), but not others, infect leukocytes by binding to a specific receptor molecule: the p-selectin glycoprotein ligand-1 (psgl-1). we find that a single amino acid residue within the capsid protein vp1 determines whether ev71 binds to psgl-1. examination of capsid sequences of representative ev71 strains revealed that the psgl-1-binding viruses had either a g or a q at residue 145 within the capsid protein vp1 (vp1-145g or q), whereas psgl-1-nonbinding viruses ha ... | 2013 | 23935488 |
| patterns of polymorphism and divergence in the vp1 gene of enterovirus 71 circulating in the asia-pacific region between 1994 and 2013. | enterovirus 71 has been implicated in several outbreaks of hand, foot and mouth disease in the asia-pacific region. the present study aimed to achieve comprehensive evolutionary dynamic aspects of ev71 during 1994-2013, based on phylogenetic analyses of the vp1 sequences. the results indicated that 4 genotypes, namely c4, c1, c2 and b4 are the predominant strains, especially in southeast asian countries. no common ancestor was shared in different countries. fourteen sites of substitutions were d ... | 2013 | 23933074 |
| plasma b-type natriuretic peptide study in children with severe enterovirus 71 infection: a pilot study. | severe enterovirus 71 (ev71) infections in children can result in acute heart failure. b-type natriuretic peptide (bnp) is a good biomarker of myocardial stress. the purpose of this study was to use plasma bnp for the detection of ev71 infection with cardiac involvement. | 2013 | 23932576 |
| [retrospective analysis of clinical and epidemiological characteristics of hand-foot-and-mouth disease deceased cases in zhejiang province]. | to understand the clinical and epidemiological characteristics of hand-foot-and-mouth disease (hfmd) deceased cases. | 2013 | 23927799 |
| genetic and antigenic characterization of enterovirus 71 in ho chi minh city, vietnam, 2011. | enterovirus 71 (ev71) frequently causes fatal infections in young children in asia. in 2011, ev71 epidemics occurred in southern vietnam. we conducted genetic and antigenic analysis of the ev71 isolates and found that 94% of them were genotype c4a related to two lineages circulating in china and 6% were genotype c5 which have circulated in vietnam since 2003. antigenic variants were not detected. ev71 vaccines are being developed. longitudinal enterovirus surveillance data are critical to formul ... | 2013 | 23922846 |
| 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. | 2014 | 23922377 |
| novel cycloalkylthiophene-imine derivatives bearing benzothiazole scaffold: synthesis, characterization and antiviral activity evaluation. | a series of novel cycloalkylthiophene-imine derivatives containing benzothiazole unit were designed, synthesized and evaluated for their anti-viral activities. the bio-evaluation results indicated that some of the target compounds (such as 5g, 5i, 5u) exhibited good to moderate antiviral effect on cvb5, adv7 and ev71 viruses, however, these compounds did not have inhibition activity against h1n1 virus. especially, the compounds 4c and 4d also exhibited high antiviral activities, which provide a ... | 2013 | 23920438 |
| development of duplex real-time rt-pcr based on taqman technology for detecting simultaneously the genome of pan-enterovirus and enterovirus 71. | human enterovirus (ev) 71 is the main etiological agent of hand, foot, and mouth disease (hfmd). it is associated with neurological complications, and caused fatalities during recent outbreaks in the asia-pacific region. infections caused by ev71 could lead to many complications, ranging from brainstem encephalitis to pulmonary oedema, resulting in high mortality. in this study, a duplex real-time rt-pcr assay was developed in order to simultaneously detect pan-ev and ev71. ev71-specific primers ... | 2013 | 23918544 |
| [recombination analysis of enterovirus 71 strain isolated in guangzhou, 2009]. | to describe the recombination features of human enterovirus 71 strain guangzhou09 isolated in guangzhou in 2009, the complete nucleotide sequences of guangzhou09 were analyzed by various of bioinformatics software. phylogenetic analysis based on p1, p2 and p3 regions indicated that recombination occurred between ev71 and cva4. phylogenetic, similarity plot and bootscan analysis further revealed the recombination between ev71 genotype c strain shanghai-fj713317 and cva4 strain hq728260 at region ... | 2013 | 23905474 |
| [the 2a protease of enterovirus 71 cleaves nup62 to inhibit nuclear transport]. | to study the impact of the enterovirus 71(ev71) on the nuclear transport mechanism,the pgfp-nls vector with nuclear location signal(nls) was constructed, rd cells transfected by the pgfp-nls vector were inoculated with the ev71 or cotransfected by ev71-2a vector. the results showed that gfp protein with nls was expressed in the cytoplasm due to the inhibition of nuclear transport. in order to further study the mechanism of the ev71 to prevent nuclear transport,nup62 was detected by western blott ... | 2013 | 23895008 |
| [research on human enterovirus 71 infectivity assay based on a real-time cell analysis]. | this research aims to evaluate the application of real - time cell assay (rtca) based on microelectronics sensor technology in the detection of hev71 induced cell lesion. growth indexes of rd cells at different stages were observed dynamically, appropriate cell concentration was selected to test hev71 infectivity and to determine the hev71 neutralizing antibody titer in serum. the traditional microplate test was used as methodology comparison and results validation at the same time. cell impedan ... | 2013 | 23895003 |
| elevated antigen-specific th2 type response is associated with the poor prognosis of hand, foot and mouth disease. | the immunopathogenesis of severe hand, foot and mouth disease (hfmd) remains elusive. this study revealed that enterovirus 71 (ev71) epitope-specific cd4+ t cell responses of hfmd patients were skewed toward a th2 cytokine profile. patients that demonstrated higher levels of il-4 expression in their cd4 t cells following antigen stimulation in vitro tended to have a more prolonged period of high fevers and a longer duration of illness. thus, an increase of ev71 epitope-specific th2 type response ... | 2013 | 23886670 |
| autoprocessing: an essential step for expression and purification of enterovirus 71 3c(pro) in escherichia coli. | a gene encoding the 3bc of human enterovirus 71 (ev71) was cloned and inserted into a derivative of plasmid pet-32a(+) driven by t7 promoter. the expressed 3c protease (3c(pro)) autocatalytically cleaved itself from the recombinant protein trx-3bc and the mature 3c(pro) partitioned in the soluble fraction of bacterial lysate. the 13-amino-acid peptide substrates with the junction of 3b/3c were used to verify the proteolysis activity of the purified 3c(pro). the ev71 3c(pro) had a km value of 63 ... | 2013 | 23881322 |
| fatal case of enterovirus 71 infection and rituximab therapy, france, 2012. | | 2013 | 23880543 |
| construction and characterization of an infectious cdna clone of enterovirus type 71 subgenotype c4. | enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease and induces fatal neurological complications. in recent years, this virus has become a major threat to public health in the asia-pacific region, while no effective antiviral therapies and vaccines are currently available. in this study, we constructed and characterized for the first time an infectious full-length ev71 cdna clone derived from the shzh98 strain, which was the first subgenotype c4 strain isolated in ... | 2013 | 23877719 |
| complete genome sequence of a human enterovirus 71 strain isolated in brunei in 2006. | the complete genome sequence of a human enterovirus 71 strain isolated in brunei in 2006 was determined. phylogenetic analysis based on the complete genome sequence classified this strain into subgenogroup b5. | 2013 | 23868136 |
| global transcriptomic analysis of human neuroblastoma cells in response to enterovirus type 71 infection. | human enterovirus type 71 (ev71) is the major pathogen of hand-foot-and-mouth disease (hfmd) and has been associated with severe neurological disease and even death in infants and young children. the pathogenesis of ev71 infection in the human central nervous system remains unclear. in this study, human whole genome microarray was employed to perform transcriptome profiling in sh-sy5y human neuroblastoma cells infected with ev71. the results indicated that ev71 infection lead to altered expressi ... | 2013 | 23861741 |
| a study of the virulence in mice of high copying fidelity variants of human enterovirus 71. | polioviruses with a g64s mutation in the 3d polymerase have enhanced replication fidelity and are attenuated in animal models. here we describe the mouse virulence properties of high replication fidelity 3d polymerase variants of human enterovirus 71 (hev71), with mutations at positions 3d-s264l, 3d-g64r or at 3d-s264l plus 3d-g64r. mouse-adapted strains (mp-g64r, mp-s264l and mp-s264l-g64r) were constructed in order to compare the virulence of the 3d polymerase variants with that of mouse-adapt ... | 2013 | 23856384 |
| [2009 evolution for vp4 of enterovirus 71 strains in shenzhen]. | to analyze the genetic evolution for the common causative agent of hand, foot and mouth disease(hfmd) that vp4 of human enterovirus 71 in shenzhen district. | 2013 | 23855119 |
| first case of severe enterovirus 71 infection in portugal. | | 2013 | 23838666 |
| 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 ... | 2013 | 23831628 |
| 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 ... | 2013 | 23827387 |
| 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 ... | 2013 | 23824683 |
| 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. | 2013 | 23809248 |
| ev71-infected cd14(+) cells modulate the immune activity of t lymphocytes in rhesus monkeys. | preliminary studies of the major pathogen enterovirus 71 (ev71), a member of the picornaviridae family, have suggested that ev71 may be a major cause of fatal hand, foot and mouth disease cases. currently, the role of the pathological changes induced by ev71 infection in the immunopathogenic response remains unclear. our study focused on the interaction between this virus and immunocytes and indicated that this virus has the ability to replicate in cd14(+) cells. furthermore, these ev71-infected ... | 2013 | 26038477 |
| 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. | 2013 | 23797008 |
| 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. ... | 2013 | 23787733 |
| hand, foot, mouth, brainstem, and heart disease resulting from enterovirus 71. | | 2013 | 23774351 |
| 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 ... | 2013 | 23769858 |
| 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 ... | 2013 | 23760234 |
| [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 ... | 2013 | 23757855 |
| [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 ... | 2013 | 23757849 |
| 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 ... | 2013 | 23755115 |
| enterovirus 71 receptors: promising drug targets? | | 2013 | 23750725 |
| 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 ... | 2013 | 23744508 |
| 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 ... | 2013 | 23727900 |
| 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 ... | 2013 | 23726823 |
| 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. | 2013 | 23726161 |
| [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- ... | 2013 | 23724645 |
| implications of age-dependent immune responses to enterovirus 71 infection for disease pathogenesis and vaccine design. | epidemics of enterovirus serotype 71 (ev71) infection in asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. efforts are underway to develop an effective ev71 vaccine. however, the immunologic correlates of protection against ev71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. severe disease and death typically occur only ... | 2013 | 26619463 |
| 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 ... | 2013 | 23711381 |
| 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 ... | 2013 | 23698055 |
| 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. | 2013 | 23685637 |
| 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 ... | 2013 | 23685430 |
| enterovirus 71 encephalitis: a new vaccine on the horizon? | | 2013 | 23668563 |
| 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 ... | 2013 | 23644889 |
| 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 ... | 2013 | 23637404 |
| 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 ... | 2013 | 23633597 |
| 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 ... | 2013 | 23622308 |
| 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 ... | 2014 | 23605689 |
| 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 ... | 2013 | 23594713 |
| 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. | 2013 | 23577963 |
| 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 ... | 2013 | 23571172 |
| 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 ... | 2013 | 23567862 |
| 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 ... | 2013 | 23561930 |
| 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 ... | 2013 | 23560917 |
| 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 ... | 2013 | 23560857 |
| 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 ... | 2013 | 23555253 |
| 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 ... | 2013 | 23555247 |
| 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. | 2013 | 23541623 |
| 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 ... | 2013 | 23535377 |
| 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 ... | 2013 | 23519962 |
| 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 ... | 2013 | 23519203 |
| 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. | 2014 | 23515152 |
| 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 ... | 2013 | 23515089 |
| 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 ... | 2013 | 23515028 |
| 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 ... | 2013 | 23509286 |
| 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 ... | 2013 | 23487447 |
| 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 ... | 2013 | 23476790 |
| 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 ... | 2013 | 23459633 |
| 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. | 2013 | 23451250 |
| 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 ... | 2013 | 23451246 |
| 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 ... | 2013 | 23441179 |
| 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 ... | 2013 | 23437282 |
| 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 ... | 2013 | 23408291 |
| 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 ... | 2013 | 23403777 |
| 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. | 2013 | 23399482 |
| 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 ... | 2013 | 23390538 |
| 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. | 2013 | 23388515 |
| 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. | 2013 | 23383215 |
| 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) ... | 2013 | 23372725 |
| 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 ... | 2013 | 23353754 |
| 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. | 2013 | 23352749 |
| 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 ... | 2013 | 23345520 |
| breastfeeding, previous epstein-barr virus infection, enterovirus 71 infection, and rural residence are associated with the severity of hand, foot, and mouth disease. | severe hand, foot, and mouth disease (hfmd) is likely to develop critical complications such as brainstem encephalitis, acute pulmonary edema, and circulatory failure, which cause child mortality during outbreaks. this study aims to investigate factors that predict the severity of hfmd. one hundred sixteen in-patient children with severe hfmd and 202 with mild hfmd were retrospectively enrolled. potential factors were collected for each child including sex, age, residence, modes of delivery, bir ... | 2013 | 23344210 |
| excretion of enterovirus 71 in persons infected with hand, foot and mouth disease. | hand, foot and mouth disease (hfmd) is a common illness in young children. it also can be seen in adults occasionally. enterovirus 71 (ev71), a pathogen that causes not only hfmd but also neurological complications and even death, has caused many hfmd outbreaks in china. however, till now the data about the duration of ev71 shedding is very limited. | 2013 | 23343115 |
| strategies to develop antivirals against enterovirus 71. | enterovirus 71 (ev71) is an important human pathogen which may cause severe neurological complications and death in children. the virus caused several outbreaks in the asia-pacific region during the past two decades and has been considered a significant public health problem in the post-poliovirus eradication era. unlike poliovirus, there is no effective vaccine or approved antivirals against ev71. to explore anti-ev71 agents therefore is of vital importance. several strategies have been employe ... | 2013 | 23339605 |
| functional comparison of scarb2 and psgl1 as receptors for enterovirus 71. | human scavenger receptor class b, member 2 (scarb2), and p-selectin glycoprotein ligand-1 (psgl1) have been identified to be the cellular receptors for enterovirus 71 (ev71). we compared the ev71 infection efficiencies of mouse l cells that expressed scarb2 (l-scarb2) and psgl1 (l-psgl1) and the abilities of scarb2 and psgl1 to bind to the virus. l-scarb2 cells bound a reduced amount of ev71 compared to l-psgl1 cells. however, ev71 could infect l-scarb2 cells more efficiently than l-psgl1 cells. ... | 2013 | 23302872 |
| rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: evaluation of antiviral efficacy in a murine infection model. | enterovirus-71 (ev71) infections can cause life-threatening diseases with neurological symptoms. currently, no direct targeting antivirals are available to combat severe ev71 infection. rupintrivir (ag7088) is a compound originally designed for rhinovirus 3c protease. previous computational analyses by us and crystallography studies by others suggested that rupintrivir is also a high affinity inhibitor to ev71 3c. thus, we aimed to further evaluate its anti-ev71 activity in vivo at clinically ac ... | 2013 | 23295352 |
| enterovirus 71 infection increases expression of interferon-gamma-inducible protein 10 which protects mice by reducing viral burden in multiple tissues. | enterovirus 71 (ev71) infection has induced fatal encephalitis in thousands of young children in the asia-pacific region over the last decade. ev71 infection continues to cause serious problems in areas with outbreaks, because vaccines and antiviral therapies are not available. lymphocytes are present in the brains of infected patients and mice, and they protect mice from infection by decreasing the viral burden. the chemokines responsible for recruiting lymphocytes to infected organs are yet to ... | 2013 | 23288420 |
| antiviral drug discovery for the treatment of enterovirus 71 infections. | enterovirus 71 (ev71) is a small, positive-sense, single-stranded rna virus in the genus enterovirus, family picornavirus. it causes hand, foot and mouth disease in infants and children, which in a small percentage of cases progresses to central nervous system infection, ranging from aseptic meningitis to fatal encephalitis. sporadic cases of ev71 infection occur throughout the world, but large epidemics have occurred recently in southeast asia and china. there are currently no approved vaccines ... | 2013 | 23261847 |
| human enterovirus 71 strains in the background population and in hospital patients in finland. | human enterovirus 71 (hev71) is a common cause of severe outbreaks of hand-foot- and mouth disease, aseptic meningitis and encephalitis in asian populations but has not caused such epidemics in all populations. | 2013 | 23261080 |