| a comprehensive procedure for antiviral inhibitor discovery using ev71 as an example. | the prevalence of chronic viral infectious diseases, the emergence and re-emergence of new viral infections, and in particular, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. in this work, we introduce a comprehensive system using enteroviruses ... | 2017 | 26942222 |
| 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. | 2014 | 25548009 |
| genetic diversity of enterovirus a71, india. | we have identified circulation of 3 genogroups of enterovirus (ev) a71 in india. a new genogroup (proposed designation g) was discovered during this study. we isolated genogroups d and g in wide geographic areas but detected subgenogroup c1 only in 1 focus in western india. a systematic nationwide search for ev-a71 is warranted. | 2015 | 25531549 |
| regulation of host responses and viral replication by the mitogen-activated protein kinases in intestinal epithelial cells infected with enterovirus 71. | enterovirus 71 (ev71) has become an important neurotropic enterovirus in children since the eradication of the poliovirus. a cytokine storm with elevated levels of proinflammatory cytokines is proposed as critical to the pathogenesis of ev71-induced brain stem encephalitis with pulmonary edema, often a fatal complication. mitogen-activated protein kinases (mapk) are involved in cellular processes including immune responses and apoptosis. ev71 infection can trigger mapk activation in human cells, ... | 2015 | 25529441 |
| a simple and highly repeatable viral plaque assay for enterovirus 71. | the classic plaque assay is a method for counting infectious viral particles, however its complexity limits its use in a variety of virological experiments. to simplify the operation and to improve the repeatability, we employed an improved plaque assay procedure based on avicel to make the whole experiment easier and optimize the results on a model of vero cells infection with enterovirus 71(ev71). clear plaques visible to the naked eyes can be formed on a 24-well plate or a 96-well plate witho ... | 2015 | 25515071 |
| 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. | 2014 | 25495312 |
| [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. | 2014 | 25481175 |
| mir-146a and mir-370 coordinate enterovirus 71-induced cell apoptosis through targeting sos1 and gadd45β. | enterovirus 71 (ev71) is an emerging life-threatening pathogen particularly in the asia-pacific region. the major pathogenic feature in ev71-infected cells is apoptosis. however, which molecular mechanism mainly contributes to ev71-induced apoptosis is not investigated thoroughly. micrornas (mirnas), the newly discovered molecules, govern a wide range of biological functions through post-transcriptional regulation including viral pathogenesis. whether mirnas and messenger rnas (mrnas) coordinate ... | 2015 | 25469565 |
| chemical modification of the plant isoprenoid cytokinin n(6)-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication. | in this study, we demonstrate that n(6)-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an ec50 of 1.0 ± 0.2 μm and a selectivity index (si) of 5.7. the synthesis of analogs with modification of the n(6)-position did not result in a lower ec50 value. however, in particular with the synthesis of n(6)-(5-hexene-2-yne-1-yl)adenosine (ec50 = 4.3 ± 1.5 μm), the selectivity index ... | 2015 | 25461889 |
| pyrrolidine dithiocarbamate inhibits enterovirus 71 replication by down-regulating ubiquitin-proteasome system. | enterovirus 71 (ev71) is the main causative pathogen of hand, foot, and mouth disease (hfmd). the severe neurological complications caused by ev71 infection and the lack of effective therapeutic medicine underline the importance of searching for antiviral substances. pyrrolidine dithiocarbamate (pdtc), an antioxidant, has been reported to inhibit the replication of coxsackievirus b (cvb) through dysregulating ubiquitin-proteasome system (ups). in this study, we demonstrated that pdtc exerted pot ... | 2015 | 25456405 |
| 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 ... | 2014 | 25448086 |
| 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 ... | 2014 | 25446894 |
| considerations for developing an immunization strategy with enterovirus 71 vaccine. | enterovirus 71 (ev71) is a common pathogen for hand, foot, and mouth disease (hfmd), which has significant morbidity and mortality, and for which children aged 6-59 months age are at highest risk. due to lack of effective treatment options, control of ev71 epidemics has mainly focused on development of ev71 vaccines. clinical trials have been completed on 3 ev71 vaccines, with trial results demonstrating good vaccine efficacy and safety. when ev71 vaccine is approved by china's national regulato ... | 2015 | 25444807 |
| 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 ... | 2014 | 25441347 |
| the enterovirus 71 procapsid binds neutralizing antibodies and rescues virus infection in vitro. | enterovirus 71 (ev71) is responsible for seasonal outbreaks of hand, foot, and mouth disease in the asia-pacific region. the virus has the capability to cause severe disease and death, especially in young children. although several vaccines are currently in clinical trials, no vaccines or therapeutics have been approved for use. previous structural studies have revealed that two antigenically distinct capsid forms are produced in ev71-infected cells: an expanded empty capsid, sometimes called a ... | 2015 | 25428877 |
| 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 ... | 2014 | 25424925 |
| biochemical characterization of recombinant enterovirus 71 3c protease with fluorogenic model peptide substrates and development of a biochemical assay. | enterovirus 71 (ev71), a primary pathogen of hand, foot, and mouth disease (hfmd), affects primarily infants and children. currently, there are no effective drugs against hfmd. ev71 3c protease performs multiple tasks in the viral replication, which makes it an ideal antiviral target. we synthesized a small set of fluorogenic model peptides derived from cleavage sites of ev71 polyprotein and examined their efficiencies of cleavage by ev71 3c protease. the novel peptide p08 [(2-(n-methylamino)ben ... | 2015 | 25421478 |
| mri findings in children with acute flaccid paralysis and cranial nerve dysfunction occurring during the 2014 enterovirus d68 outbreak. | enterovirus d68 was responsible for widespread outbreaks of respiratory illness throughout the united states in august and september 2014. during this time, several patients presented to our institution with acute flaccid paralysis and cranial nerve dysfunction. the purpose of this report is to describe the unique imaging findings of this neurologic syndrome occurring during an enterovirus d68 outbreak. | 2015 | 25414005 |
| 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 ... | 2014 | 25412347 |
| 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. | 2014 | 25410379 |
| distribution of enterovirus 71 rna in inflammatory cells infiltrating different tissues in fatal cases of hand, foot, and mouth disease. | in previous studies of hand, foot, and mouth disease patients fatally infected with enterovirus 71 (ev71), the distribution of viral protein, but not the genome, was determined. to understand the pathogenesis of ev71, however, it is important to investigate the spread of the viral genome. there have been no pathological studies of in situ ev71 viral rna in inflammatory cells infiltrating various tissues of fatal cases. we therefore first investigated the distribution and classification of inflam ... | 2015 | 25408373 |
| [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. | 2014 | 25388471 |
| [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). | 2014 | 25374082 |
| 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 ... | 2014 | 25356130 |
| 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. | 2014 | 25356127 |
| 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 ... | 2014 | 25336078 |
| 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 ... | 2014 | 25330384 |
| 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. | 2014 | 25313606 |
| 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 ... | 2014 | 25299565 |
| continuous myocloni and tonic spasms in a 2-month-old infant with enterovirus 71 brain stem encephalitis. | brain stem encephalitis is a cardinal presentation of central nervous system involvement in enterovirus 71 infection, and manifests as myoclonus, ataxia, tremor, and autonomic dysfunction. a 2-month-old infant with enterovirus 71 brain stem encephalitis demonstrated continuous myocloni and tonic spasms. on admission, the patient's myoclonus, which mainly involved the shoulders and the arms, was considerably worse during wakefulness and occurred once or twice a minute. several hours after admissi ... | 2015 | 25290724 |
| 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 ... | 2014 | 25289894 |
| prediction of signaling pathways involved in enterovirus 71 infection by algorithm analysis based on mirna profiles and their target genes. | enterovirus 71 (ev71) causes major outbreaks of hand, foot, and mouth disease. host factors and signaling pathways exhibit important functions in the ev71 life cycle. we conducted algorithm analysis based on mirna profiles and their target genes to identify the mirnas and downstream signaling pathways involved in ev71 infection. the mirna profiles of human rhabdomyosarcoma cells treated with interferon (ifn-)-α or ifn-γ were compared with those of cells infected with ev71. genes targeted by diff ... | 2015 | 25287131 |
| 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 ... | 2014 | 25275585 |
| 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 ... | 2014 | 25243194 |
| 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 ... | 2014 | 25241681 |
| [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. | 2014 | 25224238 |
| [discussion on the vaccination strategy of enterovirus type 71 vaccine]. | | 2014 | 25219429 |
| 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 ... | 2014 | 25212431 |
| [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 ... | 2014 | 25212011 |
| 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 ... | 2014 | 25202012 |
| 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 ... | 2014 | 25199773 |
| 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 ... | 2014 | 25197403 |
| proteome demonstration of alpha-1-acid glycoprotein and alpha-1-antichymotrypsin candidate biomarkers for diagnosis of enterovirus 71 infection. | human enterovirus 71 (ev71) is the major causative agents of hand-foot-and-mouth disease and frequently associated with severe complications such as encephalitis and death. understanding the host response following enteroviral infection may facilitate the development of biomarkers for ev71 infections. | 2015 | 25170552 |
| [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). | 2014 | 25146745 |
| 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 ... | 2014 | 25142603 |
| 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. | 2014 | 25139436 |
| [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 ... | 2014 | 25118374 |
| sesquiterpenoids and xanthones derivatives produced by sponge-derived fungus stachybotry sp. hh1 zsds1f1-2. | a new (2) and four known (1, 8-10) sesquiterpenoids, two new (3 and 4) and eight known (5-7, 11-15) xanthone derivatives were isolated from the cultures of sponge-derived fungus stachybotry sp. hh1 zdds1f1-2. the structure of the compounds 1-15 was determined mainly by analysis of the one-dimensional and two-dimensional nmr spectroscopic data and by analogy with the data of those reported. compound 1 was confirmed by x-ray crystallography. all the compounds were tested for their cytotoxic, antii ... | 2015 | 25118104 |
| 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 ... | 2014 | 25116390 |
| 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 ... | 2014 | 25113906 |
| 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 ... | 2014 | 25104614 |
| the cellular receptor for enterovirus 71. | | 2014 | 25103897 |
| 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 ... | 2014 | 25100827 |
| 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. | 2014 | 25097582 |
| 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 ... | 2014 | 25097545 |
| 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 ... | 2014 | 25087628 |
| 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 ... | 2014 | 25086263 |
| association of interleukin-6-572c/g gene polymorphism and serum or cerebrospinal fluid interleukin-6 level with enterovirus 71 encephalitis in chinese han patients with hand, foot, and mouth disease. | interleukin-6 (il-6), as one of pro-inflammatory cytokines, plays a key role in enterovirus 71 (ev71) encephalitis. we investigated the association of il-6-572c/g polymorphism and serum or cerebrospinal fluid (csf) il-6 level with ev71 encephalitis in patients with hand, foot, and mouth disease (hfmd). this study was carried out in 59 chinese han patients with ev71 encephalitis, 128 ev71-related hfmd without complications, and 232 controls. the il-6-572c/g polymorphism was detected by polymerase ... | 2015 | 25081498 |
| 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 ... | 2014 | 25078697 |
| mrna decay factor auf1 binds the internal ribosomal entry site of enterovirus 71 and inhibits virus replication. | au-rich element binding factor 1 (auf1) has a role in the replication cycles of different viruses. here we demonstrate that auf1 binds the internal ribosome entry site (ires) of enterovirus 71 (ev71) and negatively regulates ires-dependent translation. during ev71 infection, auf1 accumulates in the cytoplasm where viral replication occurs, whereas auf1 localizes predominantly in the nucleus in mock-infected cells. auf1 knockdown in infected cells increases ires activity and synthesis of viral pr ... | 2014 | 25077793 |
| 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. | 2014 | 25069383 |
| 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. | 2014 | 25061698 |
| 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 ... | 2014 | 25058733 |
| downregulation of microrna mir-526a by enterovirus inhibits rig-i-dependent innate immune response. | retinoic acid-inducible gene i (rig-i) is an intracellular rna virus sensor that induces type i interferon-mediated host-protective innate immunity against viral infection. although cylindromatosis (cyld) has been shown to negatively regulate innate antiviral response by removing k-63-linked polyubiquitin from rig-i, the regulation of its expression and the underlying regulatory mechanisms are still incompletely understood. here we show that rig-i activity is regulated by inhibition of cyld expr ... | 2014 | 25056901 |
| molecular epidemiology of enterovirus 71 strains isolated from children in yamagata, japan, between 1990 and 2013. | enterovirus 71 infections have become a major public issue in the asia-pacific region due to the large number of fatal cases. to clarify the longitudinal molecular epidemiology of enterovirus 71 (ev71) in a community, we isolated 240 strains from children, mainly with hand-foot-and-mouth diseases, between 1990 and 2013 in yamagata, japan. we carried out a sequence analysis of the vp1 region (891 bp) using 223 isolates and identified six subgenogroups (b2, b4, b5, c1, c2 and c4) during the study ... | 2014 | 25053796 |
| characterization of the enterovirus 71 vp1 protein as a vaccine candidate. | enterovirus 71 (ev71) is an important agent responsible for hand-foot-and-mouth disease (hfmd), which can cause severe neurological complications and death in children. however, there is no specific treatment for ev71 infection, and a safe and effective vaccine is needed urgently. in this study, an effective and economical method for the production of ev71-vp1 protein was developed, and the vp1 protein was evaluated in humoral and cellular immune responses as an ev71 vaccine. the results reveale ... | 2015 | 25043151 |
| enterovirus 71 outbreak in northern sydney, 2013: case series and initial response. | enteroviruses are a common cause of childhood disease which may manifest in a variety of ways. enterovirus 71 (ev71) is a subtype of enterovirus which can cause meningoencephalomyelitis resulting in neurological sequelae including lethargy, weakness, ataxia, sleep myoclonus, urinary retention and, in severe cases, cardiorespiratory collapse due to neurogenic pulmonary oedema. ev71 was responsible for outbreaks in south east asia in 1997-1998, in western australia in 1999 and in sydney in 2000-20 ... | 2014 | 25041293 |
| a one-step, triplex, real-time rt-pcr assay for the simultaneous detection of enterovirus 71, coxsackie a16 and pan-enterovirus in a single tube. | the recent, ongoing epidemic of hand, foot, and mouth disease (hfmd), which is caused by enterovirus infection, has affected millions of children and resulted in thousands of deaths in china. enterovirus 71 (ev71) and coxsackie a16 (ca16) are the two major distinct pathogens for hfmd. however, ev71 is more commonly associated with neurologic complications and even fatalities. therefore, simultaneously detecting and differentiating ev71 and ca16 specifically from other enteroviruses for diagnosin ... | 2014 | 25029500 |
| increased frequency of circulating follicular helper t cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection. | enterovirus 71 (ev71) is a major causative agent of hand, foot, and mouth disease (hfmd) in children. the role of t follicular helper (tfh) cells in ev71-infected children remains unclear in regulating humoral immunity. the frequency of circulating icos(high)/pd-1(high)cxcr5(+)cd4(+) tfh cells in the children with mild and severe ev71 infection and healthy controls (hc) was detected by flow cytometry, respectively. il-21 and il-6 mrna expression and their serum levels, bcl-6 mrna expression, and ... | 2014 | 25013818 |
| 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. | 2014 | 25010330 |
| 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 ... | 2014 | 25003792 |
| in vitro inhibition of enterovirus 71 infection with a nickel ion/chitosan microcomposite. | in this study, a new microcomposite composed of nickel ion and chitosan was prepared for the purpose of inhibiting enterovirus 71 (ev71) infections. a ni-chitosan (nics) microcomposite and a chitosan microcomposite (cs) were applied to treat vero cells either during or after ev71 virus adsorption. during a 72-h period of post-infection, the addition of the nics microcomposite during virus adsorption exhibited an inhibitory effect on ev71 infection. an excellent effect of over 100% average relati ... | 2014 | 24998885 |
| 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 ... | 2014 | 24997419 |
| update on the development of enterovirus 71 vaccines. | enterovirus 71 (ev71) is an etiological agent that causes severe neurological complications in children. ev71 outbreaks have occurred throughout the asia-pacific region, posing a severe global public health threat; however, no specific therapeutic strategy exists for treating ev71-infected children. | 2014 | 24989170 |
| [is enterovirus 71 vaccination also necessary in the netherlands?]. | enterovirus 71 (ev71) is an emerging infection, causing large outbreaks in asia with high morbidity and mortality in children. new vaccines against ev71 have been developed and tested in china, leading to two recent publications on the efficacy of these vaccines in the new england journal of medicine. although the results look promising, it is not expected that vaccination against ev71 will be introduced in europe any time soon. large outbreaks with high morbidity have not yet been observed in e ... | 2014 | 24988170 |
| molecular mechanism of scarb2-mediated attachment and uncoating of ev71. | unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. here we present the structural and functional studies of scarb2, a functional receptor of the important human enterovirus 71 (ev71). scarb2 is responsible for attachment as well as uncoating of ev71. difference ... | 2014 | 24986489 |
| discovery of gramine derivatives that inhibit the early stage of ev71 replication in vitro. | enterovirus 71 (ev71) is a notable causative agent of hand, foot, and mouth disease in children, which is associated with an increased incidence of severe neurological disease and death, yet there is no specific treatment or vaccine for ev71 infections. in this study, the antiviral activity of gramine and 21 gramine derivatives against ev71 was investigated in cell-based assays. eighteen derivatives displayed some degree of inhibitory effects against ev71, in that they could effectively inhibit ... | 2014 | 24979400 |
| [pentapeptides prevent enterovirus 71 proliferation in rhabdomyosarcoma cells and mice]. | enterovirus 71 (ev71) is the main causative agent of hand, foot, and mouth disease (hfmd). this article presented the inhibitory activity of pentapeptides on the ev71 infection in rhabdomyosarcoma (rd) and suckling mice. the ev71 vp1 capsid protein expression levels and mrna levels were analyzed by western blotting and real-time pcr. the antiviral activity of pentapeptides in vivo was evaluated by weight changes and ev71 vp1 protein expression levels in intestines of suckling mice. results revea ... | 2014 | 24974461 |
| apigenin inhibits enterovirus 71 replication through suppressing viral ires activity and modulating cellular jnk pathway. | enterovirus 71 (ev71) is a member of genus enterovirus in picornaviridae family, which is one of the major causative agents for hand, foot and mouth disease (hfmd), and sometimes associated with severe central nervous system diseases in children. currently there are no effective therapeutic medicines or vaccines for the disease. in this report, we found that apigenin and luteolin, two flavones that differ only in the number of hydroxyl groups could inhibit ev71-mediated cytopathogenic effect (cp ... | 2014 | 24971492 |
| [expression and activity determination of recombinant capsid protein vp2 gene of enterovirus type 71]. | to clone and express the recombinant capsid protein vp2 of enterovirus type 71 (ev71) and to identify the immune activity of expressed protein in order to build a basis for the investigation work of vaccine and diagnostic antigen. | 2014 | 24969459 |
| analysis of cross-reactive neutralizing antibodies in human hfmd serum with an ev71 pseudovirus-based assay. | hand, foot and mouth disease, associated with enterovirus 71 (ev71) infections, has recently become an important public health issue throughout the world. serum neutralizing antibodies are major indicators of ev71 infection and protective immunity. however, the potential for cross-reactivity of neutralizing antibodies for different ev71 genotypes and subgenotypes is unclear. here we measured the cross-reactive neutralizing antibody titers against ev71 of different genotypes or subgenotypes in se ... | 2014 | 24964084 |
| enterovirus 71 3c inhibits cytokine expression through cleavage of the tak1/tab1/tab2/tab3 complex. | enterovirus 71 (ev71) causes hand, foot, and mouth disease in young children and infants. severe infection with ev71 can lead to various neurological complications or fatal diseases. however, the mechanism of ev71 pathogenesis is poorly understood. emerging evidence suggests that ev71 modulates type i interferon (ifn) and cytokine responses. here, we show that ev71 disables components of the tab2 complex through the 3c protein. when expressed in mammalian cells, ev71 3c interacts with tab2 and t ... | 2014 | 24942571 |
| 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 ... | 2014 | 24937088 |
| synthetic peptides for efficient discrimination of anti-enterovirus antibodies at the serotype level. | enteroviruses are important human pathogens, causing a broad spectrum of diseases from minor common colds to fatal myocarditis. however, certain disease syndromes are caused by one or few serotypes. serotype identification is difficult due to the laborious neutralization tests that lack of sensitivity, while in commercial elisas homotypic antibodies' activities are largely masked by the recognition of genera-specific epitopes by heterotypic antibodies. in the present study homotypic assays were ... | 2014 | 24929043 |
| elucidating the host-pathogen interaction between human colorectal cells and invading enterovirus 71 using transcriptomics profiling. | enterovirus 71 (ev71) is one of the main etiological agents for hand, foot and mouth disease (hfmd) and has been shown to be associated with severe clinical manifestation. currently, there is no antiviral therapeutic for the treatment of hfmd patients owing to a lack of understanding of ev71 pathogenesis. this study seeks to elucidate the transcriptomic changes that result from ev71 infection. human whole genome microarray was employed to monitor changes in genomic profiles between infected and ... | 2014 | 24918057 |
| class i adp-ribosylation factors are involved in enterovirus 71 replication. | enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. replication of enterovirus 71 depends on host cellular factors. the viral replication complex is formed in novel, cytoplasmic, vesicular compartments. it has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. we us ... | 2014 | 24911624 |
| activation of jnk1/2 and p38 mapk signaling pathways promotes enterovirus 71 infection in immature dendritic cells. | c-jun nh2-terminal kinase/stress-activated kinase (jnk/sapk) and the p38 mitogen-activated protein kinase (p38 mapk) are important components of cellular signal transduction pathways, which have been reported to be involved in viral replication. however, little is known about jnk1/2 and p38 mapk signaling pathways in enterovirus 71 (ev71)-infected immature dendritic cells (idcs). thus, idcs were induced from peripheral blood mononuclear cells (pbmc) and performed to explore the expressions and p ... | 2014 | 24906853 |
| enterovirus 71 inhibits cellular type i interferon signaling by downregulating jak1 protein expression. | enterovirus 71 (ev71) infection can cause severe disease and lead to death in children. recurring outbreaks of ev71 have been reported in several countries. interferons (ifns) have been used for decades to treat several types of viral infection, but have a limited ability to inhibit ev71 replication. herein, we intend to investigate the mechanisms by which ev71 inhibits the cellular type i ifn response. in this study, mrc-5 (human embryonic lung fibroblast) or rd (human rhabdomyosarcoma) cells w ... | 2014 | 24905060 |
| identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections. | rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. other members of the genus can cause life-threatening acute neurological infections. there is currently no antiviral drug approved for the treatment of such infections. we have identified a series of potent, broad-spectrum antiviral compounds that inhibit the replication of the human rhinovirus, coxsackie virus, poliovirus, and enterovirus-71. the me ... | 2013 | 24900715 |
| the variations of vp1 protein might be associated with nervous system symptoms caused by enterovirus 71 infection. | the vp1 protein of enterovirus 71 (ev71) is an important immunodominant protein which is responsible for host-receptor binding. nevertheless, the relationship between vp1 and neurovirulence is still poorly understood. in this study, we investigated the relationship between mutation of vp1 and neurovirulent phenotype of ev71 infection. | 2014 | 24886383 |
| oral immunization with recombinant enterovirus 71 vp1 formulated with chitosan protects mice against lethal challenge. | enterovirus 71 (ev71) is the etiologic agent of hand-foot-and-mouth disease (hfmd) in the asia-pacific region, many strategies have been applied to develop ev71 vaccines but no vaccines are currently available. mucosal immunization of the vp1, a major immunogenic capsid protein of ev71, may be an alternative way to prevent ev71 infection. | 2014 | 24885121 |
| recombinant tandem multi-linear neutralizing epitopes of human enterovirus 71 elicited protective immunity in mice. | human enterovirus 71 (ev71) has emerged as the leading cause of viral encephalitis in children, especially in the asia-pacific regions. ev71 vaccine development is of high priority at present, and neutralization antibodies have been documented to play critical roles during in vitro and in vivo protection against ev71 infection. | 2014 | 24885030 |
| concentration and purification of enterovirus 71 using a weak anion-exchange monolithic column. | enterovirus 71 (ev-71) is a neurotropic virus causing hand, foot and mouth disease (hfmd) in infants and children under the age of five. it is a major concern for public health issues across asia-pacific region. the most effective way to control the disease caused by ev-71 is by vaccination thus a novel vaccine is urgently needed. inactivated ev-71 induces a strong, virus-neutralizing antibody response in animal models, protecting them against a lethal ev-71 challenge and it has been shown to el ... | 2014 | 24884895 |
| 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. ... | 2014 | 24875055 |
| a convenient nucleic acid test on the basis of the capillary convective pcr for the on-site detection of enterovirus 71. | the recent and continuing epidemic of enterovirus 71 in china has affected millions of children and resulted in thousands of deaths. timely diagnosis and management is essential for disease control. current enterovirus 71 molecular tests require resources that are unavailable for on-site testing. we have developed a simple-to-operate nucleic acid test, the convenient and integrated nucleic acid test, for local medical institutions. it uses a convective pcr for rapid amplification, a dipstick for ... | 2014 | 24858492 |
| complete genome sequence of a human enterovirus 71 strain isolated from a fatal case in shanghai, china, in 2012. | the complete genome sequence of a human enterovirus 71 strain (sh12-276), isolated from a fatal case in shanghai in 2012, was determined. phylogenetic analysis based on the complete genome sequence classified this strain into subgenotype c4. | 2014 | 24855303 |
| antiviral effects of two ganoderma lucidum triterpenoids against enterovirus 71 infection. | enterovirus 71 (ev71) is a major causative agent for hand, foot and mouth disease (hfmd), and fatal neurological and systemic complications in children. however, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. here, we evaluated the antiviral activities of two ganoderma lucidum triterpenoids (glts), lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (glta) and ganoderic acid y (gltb), against ev71 infection. the results showed ... | 2014 | 24845570 |
| histopathological features and distribution of ev71 antigens and scarb2 in human fatal cases and a mouse model of enterovirus 71 infection. | enterovirus 71 (ev71) is a neurotropic pathogen that causes hand, foot, and mouth disease. while infection is usually self-limiting, a minority of patients infected with ev71 develop severe neurological complications. in humans, ev71 has been reported to utilize the scavenger receptor class b, member 2 (scarb2) as a receptor for infectious cellular entry. in this study, we define the pathological features of ev71-associated disease as well as the distribution of ev71 antigen and scarb2 in human ... | 2014 | 24842162 |
| risk factors of severe hand, foot and mouth disease: a meta-analysis. | in recent years, outbreaks of hand, foot and mouth disease (hfmd) have increased, and more and more severe cases have appeared. we conducted a meta-analysis to generate large-scale evidence on the risk factors of severe hfmd. | 2014 | 24832848 |
| seroepidemiology and molecular epidemiology of enterovirus 71 in russia. | enterovirus 71 (ev71) is an emerging human pathogen causing massive epidemics of hand, foot and mouth disease with severe neurological complications in asia. ev71 also circulates in europe, however it does not cause large outbreaks. the reason for distinct epidemiological patterns of ev71 infection in europe and asia and the risk of ev71 epidemic in europe and russia remain unknown. seroepidemiology of ev71 and molecular epidemiology of occasional ev71 isolates were studied to explore circulatio ... | 2014 | 24819617 |