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complete genome sequence analysis of enterovirus 71 isolated from children with hand, foot, and mouth disease in thailand, 2012-2014.the complete genomic sequences of 14 enterovirus 71 (ev71) strains isolated from children with hand, foot, and mouth disease in thailand from 2012 to 2014 were determined and compared to enterovirus group a prototypes. phylogenetic analysis revealed that 13 strains resembled the b5 subgroup, while one strain from a fatal case designated tha_1219 belonged to the c4 subgroup. similarity plot and bootscan analyses suggested that tha_1219 underwent recombination in the p2 and p3 regions. full-genome ...201526303899
clinical features for mild hand, foot and mouth disease in china.mild hand, foot and mouth disease (hfmd) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. clinical diagnosis of mild hfmd was made by the presenting symptoms and signs (symptoms in brief) alone. we aim to evaluate the frequencies of symptoms in a retrospective case series study.201526302092
intrinsic apoptosis and proinflammatory cytokines regulated in human astrocytes infected with enterovirus 71.enterovirus 71 (ev71) has emerged as a clinically important neurotropic virus following poliovirus eradication. however, the mechanism of ev71-induced neurological manifestation remains largely unclear. in this study, we showed that human astrocytes were susceptible to ev71 and viral rna was first detected at 12 h post-infection (p.i.), whilst viral proteins were detected at 36 h p.i. ev71-infected astrocytes underwent apoptosis, in which cytochrome c was released from mitochondria to the cytoso ...201526296773
the antiviral effect of baicalin on enterovirus 71 in vitro.baicalin is a flavonoid compound extracted from scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. however, the antiviral effect of baicalin on enterovirus 71 (ev71) is still unknown. in this study, we found that baicalin showed inhibitory activity on ev71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. the expressions of ev71/3d mrna and polymerase were significantly blocked by ...201526295407
inactivated enterovirus 71 vaccine produced by 200-l scale serum-free microcarrier bioreactor system provides cross-protective efficacy in human scarb2 transgenic mouse.epidemics and outbreaks caused by infections of several subgenotypes of ev71 and other serotypes of coxsackie a viruses have raised serious public health concerns in the asia-pacific region. these concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. in this report, we present a platform for the large-scale production of a vaccine based on the inactivated ev71(e59-b4) virus. the ...201526287531
understanding enterovirus 71 neuropathogenesis and its impact on other neurotropic enteroviruses.enterovirus a71 (ev-a71) belongs to the species group a in the enterovirus genus within the picornaviridae family. ev-a71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. the pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. ev-a71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly ...201526276025
immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates.a vaccine against human enterovirus 71 (ev-a71) is urgently needed to combat outbreaks of ev-a71 and in particular, the serious neurological complications that manifest during these outbreaks. in this study, an ev-a71 virus-like-particle (vlp) based on a b5 subgenogroup (ev-a71-b5 vlp) was generated using an insect cell/baculovirus platform. biochemical analysis demonstrated that the purified vlp had a highly native procapsid structure and initial studies in vivo demonstrated that the vlps were ...201526271825
construction and characterization of infectious cdna clones of enterovirus 71 (ev71). 201526271283
replication and inhibitors of enteroviruses and parechoviruses.the enterovirus (ev) and parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, ev-a71, ev-d68, and human parechoviruses (hpev). they cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. at the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all evs and hpevs due to the great number o ...201526266417
epidemiologic and etiologic characteristics of hand, foot, and mouth disease in chongqing, china between 2010 and 2013.hand, foot, and mouth disease (hfmd) has become very common in children, with widespread occurrence across china. the aim of this study was to investigate the epidemiologic and etiologic characteristics of hfmd, including etiologic variations in chongqing, china. an epidemiologic investigation was based on 3,472 patients who presented with hfmd manifestations and were admitted at the children's hospital of chongqing medical university between 2010 and 2013. fecal specimens from 830 patients were ...201626255857
norepinephrine and epinephrine enhanced the infectivity of enterovirus 71.enterovirus 71 (ev71) infections may be associated with neurological complications, including brainstem encephalitis (be). severe ev71 be may be complicated with autonomic nervous system (ans) dysregulation and/or pulmonary edema (pe). ans dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.201526252639
enterovirus71 virus-like particles produced from insect cells and purified by multistep chromatography elicit strong humoral immune responses in mice.the study aims to develop a novel multistep chromatographic purification process for human enterovirus71 virus-like particles (vlps) produced from insect cells (sf9) infected with recombinant baculovirus.201526248815
[expression of ev71-vp1, psgl-1 and scarb2 in tissues of infants with brain stem encephalitis].to understand the correlation of enterovirus 71 (ev71), p-selectin glycoprotein ligand-1 (psgl-1), and scavenger receptor b2 (scarb2) and to explore the possible pathway and mechanism of ev71 infection by observing the expression of ev71, psgl-1 and scarb2 in tissues of infants with brain stem encephalitis.201526245084
australian national enterovirus reference laboratory annual report, 2013.australia conducts surveillance for cases of acute flaccid paralysis (afp) in children less than 15 years of age as the main method to monitor its polio-free status in accordance with the world health organization (who) recommendations. cases of afp in children are notified to the australian paediatric surveillance unit or the paediatric active enhanced disease surveillance system and faecal specimens are referred for virological investigation to the national enterovirus reference laboratory. in ...201526234257
human enterovirus nonstructural protein 2catpase functions as both an rna helicase and atp-independent rna chaperone.rna helicases and chaperones are the two major classes of rna remodeling proteins, which function to remodel rna structures and/or rna-protein interactions, and are required for all aspects of rna metabolism. although some virus-encoded rna helicases/chaperones have been predicted or identified, their rna remodeling activities in vitro and functions in the viral life cycle remain largely elusive. enteroviruses are a large group of positive-stranded rna viruses in the picornaviridae family, which ...201526218680
nuclear protein sam68 interacts with the enterovirus 71 internal ribosome entry site and positively regulates viral protein translation.enterovirus 71 (ev71) recruits various cellular factors to assist in the replication and translation of its genome. identification of the host factors involved in the ev71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. in this study, we demonstrated that the cellular factor 68-kda src-associated protein in mitosis (sam68) acts as an internal ribosome entry site (ires) trans-ac ...201526202240
quinolizidine alkaloids reduced mortality in ev71-infected mice by compensating for the levels of t cells.recent outbreak of hand, foot and mouse disease caused by enterovirus 71 is a serious threat to infants and children in asia-pacific countries. no vaccines or antiviral therapies are available against this infection. in this study, we found that quinolizidine alkaloids could improve the levels of t cells in mice. the structure-activity relationships demonstrated that the oxidation and double bonds are important for the excellent potency. oxysophocarpine, the most effective compound of six quinol ...201526189894
development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human enterovirus-71 vaccine encapsulated carrier.this study introduces a new approach for enhancing immunity toward mucosal vaccines. hev71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific iga & igg levels and viral neutralizing antibody titers. the antibody responses induced in rabbits by the different formulations delivered by a sing ...201526186664
the role of vp1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a cynomolgus monkey model.enterovirus 71 (ev71), a major causative agent of hand, foot, and mouth disease, occasionally causes severe neurological symptoms. we identified p-selectin glycoprotein ligand-1 (psgl-1) as an ev71 receptor and found that an amino acid residue 145 in the capsid protein vp1 (vp1-145) defined psgl-1-binding (pb) and psgl-1-nonbinding (non-pb) phenotypes of ev71. however, the role of psgl-1-dependent ev71 replication in neuropathogenesis remains poorly understood. in this study, we investigated vir ...201526181772
broad protection with an inactivated vaccine against primary-isolated lethal enterovirus 71 infection in newborn mice.circulating enterovirus 71 (ev-a71)-associated hand, foot, and mouth disease is on the rise in the asian-pacific region. although animal models have been developed using mouse-adapted ev-a71 strains, mouse models using primary ev-a71 isolates are scarce. lethal animal models with circulating ev-a71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation.201526169371
[molecular mechanism of action of hnrnp k and rtn3 in the replication of enterovirus 71].enterovirus 71 (ev71) is a neurotropic pathogen that can induce hand, foot and mouth disease in children. there is an appreciable mortality rate after ev71 infections. the mechanism of action of ev71 replication is not known. recent work has identified some of cell factors of the host that participate in the synthesis of the rna and proteins of ev71 (e.g., hnrnp k, reticulon 3 (rtn 3)). in that work, researchers used a competitive assay to show that hnrnp k can interact with ev71 5' utr, which i ...201526164948
[research into the pathogenicity of enterovirus 71].enterovirus 71 (ev71) is a major causative agent of hand, foot and mouth disease (hfmd). belongs to family picornaviridae, genus enterovirus, species a. ev71 infection usually affects subjects aged <5 years. hfmd caused by ev71 infection is usually mild in children. however, in some cases ev71 infection can lead to severe neurogenic disease and even death. ev71 infection has caused epidemic worldwide (especially in the asia pacific). hfmd caused by ev71 has become a major public-health prol lem ...201526164947
socioeconomic burden of hand, foot and mouth disease in children in shanghai, china.in the near future, the inactivated enterovirus 71 (ev71) vaccine is expected to become available on the market in china. since ev71 is a major cause of hand, foot and mouth disease (hfmd), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. however, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of ev71 hfmd infection. based on the 2011 population dat ...201626159305
ma104 cell line presents characteristics suitable for enterovirus a71 isolation and proliferation.enterovirus a71 (ev-a71), one of the most important causative agents of hand, foot and mouth disease (hfmd) in children, can lead to severe clinical outcomes, even death. however, the infection spectrum of ev-a71 in different cell lines remains unknown. therefore, in this study, the biological characteristics of ev-a71 subgroup c4 in different cell lines were investigated. to this end, the infectivity of ev-a71jinan1002 isolated from children with severe hfmd was assessed in 18 different host ce ...201526138857
reciprocal regulation between enterovirus 71 and the nlrp3 inflammasome.enterovirus 71 (ev71) is the major etiological agent of hand, foot, and mouth disease (hfmd). early studies showed that ev71-infected patients with severe complications exhibited elevated plasma levels of il-1β, indicating that ev71 may activate inflammasomes. our current study demonstrates that the nlrp3 inflammasome plays a protective role against ev71 infection of mice in vivo. ev71 replication in myeloid cells results in the activation of the nlrp3 inflammasome and secretion of il-1β. conver ...201526119741
[mitochondrial injury in enterovirus 71-infected vero cells and its mechanism].to investigate the mitochondrial injury in enterovirus 71 (ev71)-infected vero cells and explore the possible mechanism.201526111685
ocular pathology: role of emerging viruses in the asia-pacific region-a review.the role of viral infections in ocular pathology varies greatly, involving all the components of the eye. some viruses like herpes simplex, herpes zoster, adenovirus, enterovirus 70, influenza virus, human immunodeficiency virus, and cytomegalovirus are well-known for their role in ocular pathology. in recent years, emerging and resurging viral infections represent an important public health problem. the asia-pacific region has witnessed a number of pandemic and epidemic outbreaks caused by thes ...201726107917
[enterovirus sequencing as a new approach to the laboratory diagnosis for clinical and epidemiological purposes].introducing enterovirus sequencing as an advanced approach to classify the viruses isolated according to the novel nomenclature and to characterize isolates in detail.201526099615
an enterovirus 71 strain causes skeletal muscle damage in infected mice.to study the target organs for enterovirus 71 (ev71) in infected suckling mice.201526097530
antiviral potential of a novel compound cw-33 against enterovirus a71 via inhibition of viral 2a protease.enterovirus a71 (ev-a71) in the picornaviridae family causes hand-foot-and-mouth disease, aseptic meningitis, severe central nervous system disease, even death. ev-a71 2a protease cleaves type i interferon (ifn)-α/β receptor 1 (ifnar1) to block ifn-induced jak/stat signaling. this study investigated anti-ev-a7l activity and synergistic mechanism(s) of a novel furoquinoline alkaloid compound cw-33 alone and in combination with ifn-β anti-ev-a71 activities of cw-33 alone and in combination with if ...201526090728
hand-foot-and-mouth disease: a new look at a classic viral rash.hand-foot-and-mouth disease (hfmd) is a common cause of viral rash in children with classic skin findings which are easily recognized by pediatricians. recently, several atypical cutaneous manifestations of hfmd have been described. awareness of these patterns may lead providers to appropriate diagnosis and management. this review also highlights the epidemiological patterns of more virulent strains and emerging research in disease prevention.201526087425
phylodynamics of enterovirus a71-associated hand, foot, and mouth disease in viet nam.enterovirus a71 (ev-a71) is a major cause of hand, foot, and mouth disease (hfmd) and is particularly prevalent in parts of southeast asia, affecting thousands of children and infants each year. revealing the evolutionary and epidemiological dynamics of ev-a71 through time and space is central to understanding its outbreak potential. we generated the full genome sequences of 200 ev-a71 strains sampled from various locations in viet nam between 2011 and 2013 and used these sequence data to determ ...201526085170
[detection of cerebrospinal fluid anti-enterovirus 71 igm in children with severe hand, food and mouth disease induced by enterovirus 71 infection and its clinical significance].to detect the anti-enterovirus 71 (ev71) igm level in cerebrospinal fluid (csf) of children with severe hand, foot and mouth disease (hfmd) induced by ev71 and then analyze the relationships among the igm antibody levels, csf routine examination and patients' clinical features, and thus to evaluate the clinical significance of anti-ev71 igm as a new indicator for early diagnosis of children with severe hfmd induced by ev71.201526080665
anti-viral and cytotoxic norbisabolane sesquiterpenoid glycosides from phyllanthus emblica and their absolute configurations.in an effort to identify anti-viral and cytotoxic compounds from phyllanthus spp., 14 highly oxygenated norbisabolane sesquiterpenoids, phyllaemblicins h1-h14, were isolated from the roots of phyllanthus emblica linn, along with phyllaemblicins b and c and glochicoccinoside d. their structures were determined on the basis of detailed spectroscopic analysis and chemical methods. determination of absolute configurations of these compounds was facilitated by theoretical calculations of electronic c ...201526074492
cytokine responses and correlations thereof with clinical profiles in children with enterovirus 71 infections.severe complications associated with ev71 infections caused many infants death. however, the pathogenesis of ev71 infection in the severe cases remained poorly understood.201526058678
validation and utilization of an internally controlled multiplex real-time rt-pcr assay for simultaneous detection of enteroviruses and enterovirus a71 associated with hand foot and mouth disease.hand foot and mouth disease (hfmd) is a disease of public health importance across the asia-pacific region. the disease is caused by enteroviruses (evs), in particular enterovirus a71 (ev-a71). in ev-a71-associated hfmd, the infection is sometimes associated with severe manifestations including neurological involvement and fatal outcome. the availability of a robust diagnostic assay to distinguish ev-a71 from other evs is important for patient management and outbreak response.201526050791
monoclonal neutralizing antibodies against ev71 screened from mice immunized with yeast-produced virus-like particles.periodic outbreaks of hand, foot and mouth disease (hfmd) occur in children under 5 years old, and can cause death in some cases. the c4 strain of enterovirus 71 (ev71) is the main pathogen that causes hfmd in china. although no drugs against ev71 are available, some studies have shown that candidate vaccines or viral capsid proteins can produce anti-ev71 immunity. in this study, female babl/c mice (6-8 weeks old) were immunized with virus-like particles (vlps) of ev71 produced in yeast to scree ...201526040893
the approved pediatric drug suramin identified as a clinical candidate for the treatment of ev71 infection-suramin inhibits ev71 infection in vitro and in vivo.enterovirus 71 (ev71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. there is an urgent unmet medical need for new pharmaceutical agents to control ev71 infections. using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked ev71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. moreover, we de ...201426038755
receptors for enterovirus 71.enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease (hfmd). occasionally, ev71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. several molecules act as cell surface receptors that stimulate ev71 infection, including scavenger receptor b2 (scarb2), p-selectin glycoprotein ligand-1 (psgl-1), sialylated glycan, heparan sulfate and annexin ii (anx2). scarb2 plays critica ...201426038749
a neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses.vaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain bj110, which has a c4 genotype. porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. oral and combined oral-nasal infection of 5-day-old neonatal gnotobiotic pigs with 5×10( ...201426038741
neutralizing antibody responses to enterovirus and adenovirus in healthy adults in china.hand, foot and mouth disease (hfmd) is an important public health problem that has emerged over the past several years. hfmd predominantly infects children under seven years old and occasionally causes severe disease in adults. among the enteroviruses, enterovirus 71 (ev71) and coxsackievirus 16 (ca16) are the major causative agents of hfmd. in addition, adenovirus cocirculates with enterovirus and has become a possible additional pathogenic factor for hfmd in some cases. here, we have investiga ...201426038738
enterovirus 71 infection in children with hand, foot, and mouth disease in shanghai, china: epidemiology, clinical feature and diagnosis.in 2012 a large outbreak of hand, foot, and mouth disease (hfmd) widely spread over china, causing more than 2 million cases and 567 deaths. our purpose was to characterize the major pathogens responsible for the 2012 hfmd outbreak and analyze the genetic characterization of the enterovirus 71 (ev71) strains in shanghai; also, to analyze the dynamic patterns of neutralizing antibody (nab) against ev71 and evaluate the diagnostic value of several methods for clinical detection of ev71.201526036928
immunogenicity and protective efficacy of an ev71 virus-like particle vaccine against lethal challenge in newborn mice.enterovirus 71(ev71) has caused severe epidemics of hand, foot and mouth disease (hfmd) in the asia pacific in recent years, particularly in infants and pre-school children. it has become a serious public health threat, as currently there are no approved vaccines or antiviral drugs for ev71 infection. many ev71 vaccines have been under development worldwide, however the main focus is inactivated ev71 vaccines. for example, the inactivated ev71 vaccine has recently finished phase iii clinical tri ...201526036916
epidemiological characteristics and influential factors of hand, foot and mouth disease (hfmd) reinfection in children in anhui province.hand, foot and mouth disease (hfmd) is an acute contagious condition caused by a spectrum of human enteroviruses. hfmd reinfection is common in the absence of cross-protection from other virus subtypes. this study focused on reinfection in children in anhui province, china between 2008 and 2013 using surveillance system data. we classified 8960 cases as reinfected, corresponding to a rate of 2·02%. the reinfection rate was higher in boys than in girls [odds ratio (or) 1·27, 95% confidence interv ...201626027435
determinants of ev71 immunogenicity and protection against lethal challenge in a mouse model.circulating enterovirus 71 (ev71)-associated hand, foot, and mouth disease (hfmd) is a major public health problem in the asian-pacific region. an ev71 vaccine for hfmd prevention is currently being developed. however, viral determinants that could influence the vaccine's efficacy have not been well characterized. in this study, we isolated and characterized several ev71 strains that are currently circulating in northern and southern china. we determined that vp1 variation is a major determinant ...201526025091
characterization of the antibody response against ev71 capsid proteins in chinese individuals by neibm-elisa.human enterovirus 71 (ev71) has become the major pathogen of hand, foot, and mouth disease (hfmd) worldwide, while the anti-ev71 antibody responses other than neutralizing epitopes have not been characterized. in this study, ev71 capsid proteins vp1, vp3, vp0 and various vp1 antigens were constructed to analyze anti-ev71 response in severe hfmd cases, non-hfmd outpatient children and normal adults using a novel evolved immunoglobulin-binding molecule (neibm)-based elisa. the high prevalence of a ...201526023863
molecular epidemiology and evolution of human enterovirus 71 and hand, foot and mouth disease.human enterovirus 71(ev71), one of the major pathogens of the hand, foot and mouth disease (hfmd), causes skin rashes in palms, feet and mouth ulcers and complication in the central nervous system such as aseptic meningitis and acute flaccid paralysis that may lead to death. ev71 infection has been reported to be associated with many outbreaks of hfmd worldwide, especially the great outbreaks that occurred in the asia-pacific region and caused numerous death since 1997. the studies of molecular ...201525998430
generation and characterization of a protective mouse monoclonal antibody against human enterovirus 71.human enterovirus 71 (ev71) infection has emerged as a major threat to children; however, no effective antiviral treatment or vaccine is currently available. antibody-based treatment shows promises to control this growing public health problem of ev71 infection, and a few potent monoclonal antibodies (mabs) targeting viral capsid protein have been well described. here, we generated an ev71-specific mouse mab 2g8 that conferred full protection against lethal ev71 challenge in a suckling mouse mod ...201525967656
therapeutic and prevention strategies against human enterovirus 71 infection.human enterovirus 71 (hev71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. there has been an increase in hev71 epidemic activity throughout the asia-pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. to date there is no effective antiviral treatment and no vaccine is available to prevent hev71 infection. the in ...201525964873
development of ev71 virus-like particle purification processes.enterovirus 71 (ev71) causes the outbreaks of hand-foot-and-mouth disease and results in deaths of hundreds of young children. ev71 virus-like particles (vlps) are empty capsids consisting of viral structural proteins and can elicit potent immune responses, thus holding promise as an ev71 vaccine candidate. however, an efficient, scalable production and purification scheme is missing. for mass production of ev71 vlps, this study aimed to develop a production and chromatography-based purification ...201525939279
protective effect of enterovirus‑71 (ev71) virus‑like particle vaccine against lethal ev71 infection in a neonatal mouse model.enterovirus-71 (ev71) is a viral pathogen that causes severe cases of hand, foot and mouth disease (hfmd) among young children, with significant mortality. effective vaccines against hfmd are urgently required. several ev71 virus-like particle (vlp) vaccine candidates were found to be protective in the neonatal mouse ev71 challenge model. however, to what extent the vlp vaccine protects susceptible organs against ev71 infection in vivo has remained elusive. in the present study, the comprehensiv ...201525936344
enterovirus 71 proteins 2a and 3d antagonize the antiviral activity of gamma interferon via signaling attenuation.enterovirus 71 (ev71) infection causes severe mortality involving multiple possible mechanisms, including cytokine storm, brain stem encephalitis, and fulminant pulmonary edema. gamma interferon (ifn-γ) may confer anti-ev71 activity; however, the claim that disease severity is highly correlated to an increase in ifn-γ is controversial and would indicate an immune escape initiated by ev71. this study, investigating the role of ifn-γ in ev71 infection using a murine model, showed that ifn-γ was el ...201525926657
saururus chinensis (lour.) baill blocks enterovirus 71 infection by hijacking mek1-erk signaling pathway.the aerial parts of saururus chinensis (lour.) baill are a chinese herbal medicine used for the treatment of edema and inflammatory diseases. however, the effect of this medicine on enterovirus 71 (ev71) infection has not been explored. previous studies showed that mek1-erk signal pathway was required for efficient replication of ev71 infection and inhibition of this signal pathway has been shown to suppress virus infection. here we show that the water extract of s. chinensis (lour.) baill (scb) ...201525912818
differential expression of mirnas in enterovirus 71-infected cells.enterovirus 71 (ev71) is one of the major etiological pathogens of hand, foot and mouth disease (hfmd) and can cause severe cerebral and pulmonary complications and even fatality. micrornas (mirnas), a class of small non-coding rna molecules, play an important role in post-transcriptional regulation of gene expression and thereby influencing various physiological and pathological processes. increasing evidence suggests that mirnas act as key effector molecules in the complicated pathogen-host in ...201525889836
update on hand-foot-and-mouth disease.hand-foot-and-mouth disease is a viral exanthem caused, primarily by coxsackie a16 and enterovirus 71 with typical clinical features of fever, painful papules and blisters over the extremities and genitalia and an enanthem involving ulceration of the mouth, palate, and pharynx. other enteroviruses have recently been noted to cause severe neurologic illness and paralysis (enterovirus 68) with variable cutaneous features. a recent outbreak of coxsackie a6 infection has been seen worldwide with cas ...201525889136
[epidemiological characteristics of enterovirus type 71 diseases].the objective of this study was to investigate the epidemiological characteristics of disease caused by enterovirus type 71.201525876864
[hand-foot-mouth disease pathogen separation and ev71 vp1 gene analysis in sanmenxia city, henan province, china].the aim of this study was to understand the enterovirus types and biological features of pediatric cases of hfmd in sanmenxia city during 2011, and compare the latter to a cohort of healthy children. stool samples of 55 cases of hfmd and 60 healthy children were collected for the isolation and identification of enteroviruses using rna extraction and real-time rt-pcr assays. ev71 and ca16 were identified by nucleotide sequencing using virus-specific vp1 primers; for the other enteroviruses, 012/0 ...201425868277
scarb2/limp-2 regulates ifn production of plasmacytoid dendritic cells by mediating endosomal translocation of tlr9 and nuclear translocation of irf7.scavenger receptor class b, member 2 (scarb2) is essential for endosome biogenesis and reorganization and serves as a receptor for both β-glucocerebrosidase and enterovirus 71. however, little is known about its function in innate immune cells. in this study, we show that, among human peripheral blood cells, scarb2 is most highly expressed in plasmacytoid dendritic cells (pdcs), and its expression is further upregulated by cpg oligodeoxynucleotide stimulation. knockdown of scarb2 in pdc cell lin ...201525862818
downregulation of viral rna translation by hepatitis c virus non-structural protein ns5a requires the poly(u/uc) sequence in the 3' utr.hepatitis c virus (hcv) non-structural protein 5a (ns5a) is essential for viral replication; however, its effect on hcv rna translation remains controversial partially due to the use of reporters lacking the 3' utr, where ns5a binds to the poly(u/uc) sequence. we investigated the role of ns5a in hcv translation using a monocistronic rna containing a renilla luciferase gene flanked by the hcv utrs. we found that ns5a downregulated viral rna translation in a dose-dependent manner. this downregulat ...201525862017
massive pulmonary hemorrhage in enterovirus 71-infected hand, foot, and mouth disease.hand, foot, and mouth disease (hfmd) is an acute, mostly self-limiting infection. patients usually recover without any sequelae. however, a few cases are life threatening, especially those caused by enterovirus 71 (ev71). a 12-month-old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth, hands, and feet. after 3 days, he experienced 3 seizure episodes and was referred to our hospital. on admission, he was conscious and his chest radiograph was normal. howev ...201525861335
clinical analysis of 134 children with nervous system damage caused by enterovirus 71 infection.the purpose of this study was to evaluate the clinical characteristics of nervous system damage caused by enterovirus 71 (ev71) infection in pediatric patients.201525860536
risk factors for severe hand-foot-mouth disease in children in hainan, china, 2011-2012.the incidence of severe/fatal cases of hand-foot-mouth disease (hfmd) has increased in south asia. in china, hainan province had the highest incidence of mortality associated with hfmd in 2011. this study investigated the risk factors for severe hfmd in hainan. the hfmd survey database for hainan province for 2011 and 2012 was analyzed, and the biological and behavioral characteristics of severe (n = 980) and nonsevere (n = 1679) hfmd were compared. the association between each explanatory varia ...201525850695
development of a stable gaussia luciferase enterovirus 71 reporter virus.we report a stable gaussia luciferase enterovirus 71 (gluc-ev71) reporter virus to facilitate drug discovery. the gluc-ev71 reporter virus was generated by engineering the gaussia luciferase (gluc) gene between the 5' untranslated region and vp4 gene of the ev71 genome. we could recover gluc-ev71 after transfection of vero cells with the cdna clone-derived rna. the reporter virus efficiently infects and replicates in various cell types (vero, human rhabdomyosarcoma, and hela cells), producing ro ...201525843263
type i interferon related genes are common genes on the early stage after vaccination by meta-analysis of microarray data.the objective of this study was to find common immune mechanism across different kinds of vaccines. a meta-analysis of microarray datasets was performed using publicly available microarray gene expression omnibus (geo) and array express data sets of vaccination records. seven studies (out of 35) were selected for this meta-analysis. a total of 447 chips (145 pre-vaccination and 302 post-vaccination) were included. significance analysis of microarrays (sam) program was used for screening differen ...201525839220
identification of a common epitope between enterovirus 71 and human med25 proteins which may explain virus-associated neurological disease.enterovirus 71 (ev71) is a major causative pathogen of hand, foot and mouth disease with especially severe neurologic complications, which mainly account for fatalities from this disease. to date, the pathogenesis of ev71 in the central neurons system has remained unclear. cytokine-mediated immunopathogenesis and nervous tissue damage by virus proliferation are two widely speculated causes of the neurological disease. to further study the pathogenesis, we identified a common epitope (co-epitope) ...201525826188
elevated cerebrospinal fluid endothelin 1 associated with neurogenic pulmonary edema in children with enterovirus 71 encephalitis.neurogenic pulmonary edema (npe) is a fatal complication in children with enterovirus 71 (ev71) encephalitis. endothelin 1 (et-1), a potent vasoconstrictor, can induce pulmonary edema in rats via intrathecal injections. thus, it was hypothesized that et-1 in the central nervous system may correlate with npe in children with ev71 encephalitis.201525820093
high-yield production of recombinant virus-like particles of enterovirus 71 in pichia pastoris and their protective efficacy against oral viral challenge in mice.enterovirus 71 (ev71) is one of the major causative pathogens of hand, foot and mouth disease (hfmd), which is highly prevalent in the asia-pacific regions. severe hfmd cases with neurological complications and even death are often associated with ev71 infections. however, no licensed ev71 vaccine is currently available. recombinant virus-like particles (vlps) of ev71 have been produced and shown to be a promising vaccine candidate in preclinical studies. however, the performance of current reco ...201525820068
ev71 infection correlates with viral igg preexisting at pharyngo-laryngeal mucosa in children.enterovirus 71 (ev71) infection causes severe central nervous system damage, particularly for children under the age of 5 years old, which remains a major public health burden worldwide. clinical data released that children may be repeatedly infected by different members in enterovirus and get even worsen. mucosa, especially epithelium of alimentary canal, was considered the primary site of ev71 infection. it has been elusive whether the preexsiting viral antibody in mucosa plays a role in ev71 ...201525813631
enterovirus a71 subgenotype b5, france, 2013. 201525811300
both erk1 and erk2 are required for enterovirus 71 (ev71) efficient replication.it has been demonstrated that mek1, one of the two mek isoforms in raf-mek-erk1/2 pathway, is essential for successful ev71 propagation. however, the distinct function of erk1 and erk2 isoforms, the downstream kinases of meks, remains unclear in ev71 replication. in this study, specific erk sirnas and selective inhibitor u0126 were applied. silencing specific erk did not significantly impact on the ev71-caused biphasic activation of the other erk isoform, suggesting the ev71-induced activations ...201525803100
peptidomimetic ethyl propenoate covalent inhibitors of the enterovirus 71 3c protease: a p2-p4 study.enterovirus 71 (ev71) is a highly infectious pathogen primarily responsible for hand, foot, and mouth disease, particularly among children. currently, no approved antiviral drug has been developed against this disease. the ev71 3c protease is deemed an attractive drug target due to its crucial role in viral polyprotein processing. rupintrivir, a peptide-based inhibitor originally developed to target the human rhinovirus 3c protease, was found to inhibit the ev71 3c protease. in this communicatio ...201625792507
proteomics analysis of ev71-infected cells reveals the involvement of host protein nedd4l in ev71 replication.enterovirus 71 (ev71) is a human enterovirus that has seriously affected the asia-pacific area for the past two decades. ev71 infection can result in mild hand-foot-and-mouth disease and herpangina and may occasionally lead to severe neurological complications in children. however, the specific biological processes that become altered during ev71 infection remain unclear. to further explore host responses upon ev71 infection, we identified proteins differentially expressed in ev71-infected human ...201525785312
enterovirus 71 induces apoptosis of sh‑sy5y human neuroblastoma cells through stimulation of endogenous microrna let-7b expression.enterovirus 71 (ev71) is a pathogenic microorganism that causes hand, foot and mouth disease. however, the epigenetic mechanisms behind how ev71 regulates host cell proliferation and apoptosis are unclear. in the present study, the ability of ev71 to induce apoptosis was analyzed in the sh-sy5y human neuroblastoma cell line and the effect of this virus on the mrna expression levels of various apoptotic markers, mirna let-7b and cyclin d1 (ccnd1), was also investigated. the results demonstrated t ...201525779425
reemergence of enterovirus 71 epidemic in northern taiwan, 2012.enterovirus 71 (ev71) belongs to picornavirus family and could be classified phylogenetically into three major genogroups (a, b and c) including 11 genotypes (a, b1-b5 and c1-c5). since 1997, ev71 has caused large-scale of epidemics with neurological complications in asian children. in taiwan, nationwide ev71 epidemics with different predominant genotypes have occurred cyclically since 1998. a nationwide ev71 epidemic occurred again in 2012. we conducted genetic and antigenic characterizations o ...201525774888
magnesium lithospermate b and rosmarinic acid, two compounds present in salvia miltiorrhiza, have potent antiviral activity against enterovirus 71 infections.the aim of this study was to identify the active ingredients responsible for the anti-ev71 activity produced by salvia miltiorrhiza extracts. a pgs-ev71 ires-based bicistronic reporter assay platform was used for rapid analysis of compounds that could specifically inhibit ev71 viral ires-mediated translation. the analysis identified 2 caffeic acid derivatives, magnesium lithospermate b (mlb) and rosmarinic acid (ra), which suppressed ev71 ires-mediated translation at concentrations of 30μg/ml. w ...201525773498
gitrl as a genetic adjuvant enhances enterovirus 71 vp1 dna vaccine immunogenicity.vp1 protein is the immunodominant capsid protein of enterovirus 71 (ev71) which is responsible for large outbreaks of hand, foot and mouth disease. it has been reported that glucocorticoid-induced tumor necrosis factor receptor-related protein (gitr) and its ligand (gitrl) are involved in modulating both innate and adaptive immune responses. in this study, a dna vaccine vector encoding ev71 vp1 gene and mgitrl gene (pires/vp1/mgitrl) was constructed. and female balb/c mice were immunized intramu ...201525772201
enterovirus 71 infection causes severe pulmonary lesions in gerbils, meriones unguiculatus, which can be prevented by passive immunization with specific antisera.neurogenic pulmonary edema caused by severe brainstem encephalitis is the leading cause of death in young children infected by enterovirus 71 (ev71). however, no pulmonary lesions have been found in ev71-infected transgenic or non-transgenic mouse models. development of a suitable animal model is important for studying ev71 pathogenesis and assessing effect of therapeutic approaches. we had found neurological disorders in ev71-induced young gerbils previously. here, we report severe pulmonary le ...201525767882
association of enterovirus 71 encephalitis with the interleukin-8 gene region in chinese children.the study was performed in 36 chinese patients with enterovirus 71 (ev71) encephalitis and 141 patients with ev71-related hand, foot and mouth disease (hfmd) without encephalitis. genotyping was determined by polymerase chain reaction- restriction fragment length polymorphism. patients with ev71 encephalitis had a significantly higher frequency of interleukin-8 (il-8)-251tt genotype than patients with ev71-related hfmd without encephalitis (55.6% vs 31.2%, p = 0.023). the frequency of il-8-251t ...201525751776
early growth response-1 facilitates enterovirus 71 replication by direct binding to the viral genome rna.enterovirus 71 (ev71) infections can cause hand, foot and mouth disease (hfmd), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children. unfortunately, there is currently no effective treatment for ev71 infection due to the lack of understanding of viral replication and infection; and viral infections have emerged as an imperative global hazard. thus, it is extremely important to understand the mechanism of ev71 replication in order to prevent and control the diseases assoc ...201525724735
case-fatality of hand, foot and mouth disease associated with ev71: a systematic review and meta-analysis.hand, foot and mouth disease (hfmd) associated with enterovirus 71 (ev71) is a growing public health concern. this study aimed to estimate the case-fatality of hfmd associated with ev71 on the basis of a meta-analysis. we searched pubmed, cochrane, web of science, elsevier, cnki, wanfang, and vip databases. two authors independently selected relevant studies. the pooled estimate of case-fatality was calculated using a random-effects model. potential sources of heterogeneity were explored using s ...201525721492
the role of lipid rafts in the early stage of enterovirus 71 infection.although it has been widely accepted that enterovirus 71 (ev71) enters permissive cells via receptor-mediated endocytosis, the details of entry mechanism for ev71 still need more exploration. this study aimed to investigate the role of lipid rafts in the early stage of ev71 infection.201525720437
a potent virus-specific antibody-secreting cell response to acute enterovirus 71 infection in children.enterovirus 71 (ev71) remains a leading pathogen for acute infectious diseases in children, especially in asia. the cellular basis for establishing a virus-specific antibody response to acute ev71 infections is unclear in children.201525712974
risk factors of severe hand, foot and mouth disease complicated with cardiopulmonary collapse.the aim of this study was to investigate the risk factors for severe hand, foot and mouth disease (hfmd) complicated with cardiopulmonary collapse in children.201525712793
differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype ev-a71 in crossing an in vitro model of the human blood-brain barrier.human cerebral microvascular endothelial cells (hcmec/d3 cell line) form a steady polarized barrier when cultured in vitro on a permeable membrane. their susceptibility to enterovirus (ev) strains was analysed to investigate how these viruses may cross the blood-brain barrier. a sample of 88 virus strains was selected on phylogenetic features amongst 43 epidemiologically relevant types of the four ev species a-d. the ev-a71 genome was replicated at substantial rates, whilst the infectious virus ...201525711966
enterovirus 71 virion-associated galectin-1 facilitates viral replication and stability.enterovirus 71 (ev71) infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. several severe ev71 endemics have occurred in asia-pacific region, including taiwan, and have become a serious threat to children's health. ev71 infection is initiated by the attachment of the virion to the target cell surface. although this process relies primarily upon interaction between viruses and cell surface rece ...201525706563
a generic assay for whole-genome amplification and deep sequencing of enterovirus a71.enterovirus a71 (ev-a71) has emerged as the most important cause of large outbreaks of severe and sometimes fatal hand, foot and mouth disease (hfmd) across the asia-pacific region. ev-a71 outbreaks have been associated with (sub)genogroup switches, sometimes accompanied by recombination events. understanding ev-a71 population dynamics is therefore essential for understanding this emerging infection, and may provide pivotal information for vaccine development. despite the public health burden of ...201525704598
rassf4 promotes ev71 replication to accelerate the inhibition of the phosphorylation of akt.enterovirus 71 (ev71) is a neurotropic virus that causes hand, foot and mouth disease (hfmd), occasionally leading to death. as a member of the ras association domain family (rassfs), rassf4 plays important roles in cell death, tumor development and signal transduction. however, little is known about the relationship between rassf4 and ev71. our study reveals for the first time that rassf4 promotes ev71 replication and then accelerates akt phosphorylation inhibition in ev71-infected 293t cells, ...201525701784
resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking ikks/nf-κb signaling pathway.polydatin and resveratrol, as major active components in polygonum cuspidatum, have anti-inflammatory, antioxidant and antitumor functions. however, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (ev71) have not been reported. in this study, resveratrol revealed strong antiviral activity on ev71, while polydatin had weak effect. neither polydatin nor resveratrol exhibited influence on viral attachment. resveratrol could effectively inhibit the synthesis of ev71/vp1 and t ...201525692777
peptidyl aldehyde nk-1.8k suppresses enterovirus 71 and enterovirus 68 infection by targeting protease 3c.enterovirus (ev) is one of the major causative agents of hand, foot, and mouth disease in the pacific-asia region. in particular, ev71 causes severe central nervous system infections, and the fatality rates from ev71 infection are high. moreover, an outbreak of respiratory illnesses caused by an emerging ev, ev68, recently occurred among over 1,000 young children in the united states and was also associated with neurological infections. although enterovirus has emerged as a considerable global p ...201525691647
predicting severe enterovirus 71 infection: age, comorbidity, and parental behavior matter.enterovirus 71 (ev71) is one of the major pathogens that cause severe enteroviral infections. our aim was to study the behavioral and household risk factors for its serious complications.201725678038
analysis of synonymous codon usage in enterovirus 71.enterovirus 71 (ev71) is the major cause of hand-foot-and-mouth disease in children. in our study, using the complete genome sequences of 42 ev71 representing all three genotypes, we analyzed synonymous codon usage and the relative dinucleotide abundance in ev71 genome. the general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in ev71 genome. furthermore, we observe ...201425674591
cell surface nucleolin facilitates enterovirus 71 binding and infection.because the pathogenesis of enterovirus 71 (ev71) remains mostly ambiguous, identifying the factors that mediate viral binding and entry to host cells is indispensable to ultimately uncover the mechanisms that underlie virus infection and pathogenesis. despite the identification of several receptors/attachment molecules for ev71, the binding, entry, and infection mechanisms of ev71 remain unclear. herein, we employed glycoproteomic approaches to identify human nucleolin as a novel binding recept ...201525673703
spatio-temporal epidemiology of hand, foot and mouth disease in liaocheng city, north china.hand, foot and mouth disease (hfmd) has posed a notable threat to public health and become a public health priority in china. this study was based on the reported cases of hfmd between 2007 and 2011. a total of 34,176 hfmd cases were geo-coded at town level (n=134). firstly, a descriptive analysis was conducted to evaluate the epidemic characteristics of hfmd. then, the kulldorff scan statistic based on a discrete poisson model was used to detect spatial-temporal clusters. spatial distribution o ...201525667633
correlation of an interleukin-4 gene polymorphism with susceptibility to severe enterovirus 71 infection in chinese children.enterovirus 71 (ev71) has caused many outbreaks of diseases among children worldwide since it was first reported in 1974, but its mechanism of pathogenesis remains unclear. this study was designed to investigate the possible association of the il-4 -589c/t gene polymorphism with severity of ev71 infection in chinese children. the il-4 -589c/t gene polymorphism was detected in ev71-infected subjects (n = 185), including those with mild cases (n = 102) and severe cases (n = 83) as well as healthy ...201525666199
systemic antibody response to nano-size calcium phospate biocompatible adjuvant adsorbed hev-71 killed vaccine.since 1980s, human enterovirus-71 virus (hev-71) is one of the common infectious disease in asian pacific region since late 1970s without effective commercial antiviral or protective vaccine is unavailable yet. the work examines the role of vaccine adjuvant particle size and the route of administration on postvaccination antibody response towards hev-71 vaccine adsorbed to calcium phosphate (cap) adjuvant.201525649429
tlr3 signaling in macrophages is indispensable for the protective immunity of invariant natural killer t cells against enterovirus 71 infection.enterovirus 71 (ev71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. the mechanisms that determine the age-dependent susceptibility remain largely unclear. here, we found that the paucity of invariant natural killer t (inkt) cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to ev71 infection. inkt cells were crucial antiviral effector cells to protect young mice from ...201525615690
cerebrospinal fluid th1/th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.enterovirus 71 (ev71) infection can cause severe neurological complications including meningoencephalitis (me) in some patients with hand, foot and mouth disease (hfmd). however, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with me following ev71 infection. in this study, responses of th1/th2 cytokine, including il-2, il-4, il-6, il-10, tnf-α and ifn-γ, in cerebrospinal fluid (csf) from patients with ev71-related h ...201525611005
lysosomal integral membrane protein type-2 (limp-2/scarb2) is a substrate of cathepsin-f, a cysteine protease mutated in type-b-kufs-disease.the lysosomal integral membrane protein type-2 (limp-2/scarb2) has been identified as a receptor for enterovirus 71 uptake and mannose-6-phosphate-independent lysosomal trafficking of the acid hydrolase β-glucocerebrosidase. here we show that limp-2 undergoes proteolytic cleavage mediated by lysosomal cysteine proteases. heterologous expression and in vitro studies suggest that cathepsin-f is mainly responsible for the lysosomal processing of wild-type limp-2. furthermore, examination of purifie ...201525576872
detection of hand, foot and mouth disease in the yucatan peninsula of mexico.we report a case of hand, foot and mouth disease (hfmd) in a 5-year-old male from merida city in the yucatan peninsula of mexico. a clinical and physical examination revealed that the patient had symptoms typical of hfmd, including fever, fatigue, odynophagia, throat edema, hyperemia, lesions on the hands and feet, and blisters in the oral cavity. the patient fully recovered after a convalescence period of almost three weeks. reverse transcription-polymerase chain reaction and nucleotide sequenc ...201425568757
[research methods in protein-protein and protein-nucleic acid interactions and application in the study of human enterovirus a71].methods for analyses of protein-protein interactions include: yeast two hybrid (y2h), phage dis- play (pd), co-immunoprecipitation (co-ip), glutathione s-transferase pull-down (gst pull-down), cellular co-localization, far-western blotting, virus overlay protein binding assay (vopba), surface plasmon resonance (spr), and fluorescence resonance energy transfer (fret). technologies for the detection of protein-nucleic acid interactions include: yeast one hybrid (y1h), chromatin immunoprecipitation ...201425562971
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