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coxsackievirus a6 associated hand, foot and mouth disease in adults: clinical presentation and review of the literature.hand, foot, and mouth disease (hfmd) is generally considered a rare illness in adults. classically, hfmd has been strongly associated with coxsackievirus strain a16 and enterovirus 71. the coxsackievirus a6 (cva6) strain has been linked to severe worldwide outbreaks since 2008. cva6 is associated with a more severe and profound course of disease, affecting both children and adults.201424932735
[hand, foot and mouth disease--more than a harmless "childhood disease"].hand, foot and mouth disease (hfmd) is a highly contagious, world-wide distributed viral illness that affects predominantly children. it is caused by several enteroviruses, such as coxsackieviruses a6, a10, a16 and enterovirus 71. in most cases, hfmd follows a benign and self-limiting course. after an incubation period of 3 to 10 days, fever and sore throat, the first symptoms of the disease, appear. a few days later, maculopapular or vesicular eruptions form on the palms and soles as well as in ...201424490433
atypical hand-foot-and-mouth disease associated with coxsackievirus a6 infection.hand-foot-and-mouth disease (hfmd) is an acute viral illness commonly caused by coxsackievirus (cv)-a16 and enterovirus 71 infections. recently, atypical hfmd has been reported in association with cv-a6, an uncommon enterovirus strain.201324035209
combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change.fitting of atomic components into electron cryo-microscopy (cryoem) density maps is routinely used to understand the structure and function of macromolecular machines. many fitting methods have been developed, but a standard protocol for successful fitting and assessment of fitted models has yet to be agreed upon among the experts in the field. here, we created and tested a protocol that highlights important issues related to homology modelling, density map segmentation, rigid and flexible fitti ...201424333899
structural and functional analysis of coxsackievirus a9 integrin αvβ6 binding and uncoating.coxsackievirus a9 (cva9) is an important pathogen of the picornaviridae family. it utilizes cellular receptors from the integrin αv family for binding to its host cells prior to entry and genome release. among the integrins tested, it has the highest affinity for αvβ6, which recognizes the arginine-glycine-aspartic acid (rgd) loop present on the c terminus of viral capsid protein, vp1. as the atomic model of cva9 lacks the rgd loop, we used surface plasmon resonance, electron cryo-microscopy, an ...201323365426
human astrocytic cells support persistent coxsackievirus b3 infection.enteroviruses can frequently target the human central nervous system to induce a variety of neurological diseases. although enteroviruses are highly cytolytic, emerging evidence has shown that these viruses can establish persistent infections both in vivo and in vitro. here, we investigated the susceptibility of three human brain cell lines, ccf-sttg1, t98g, and sk-n-sh, to infection with three enterovirus serotypes: coxsackievirus b3 (cvb3), enterovirus 71, and coxsackievirus a9. persistent inf ...201324027313
enteroviruses in the early 21st century: new manifestations and challenges.enteroviruses cause a wide variety of diseases with neurologic, respiratory, skin, and gastrointestinal findings. the purpose of this review is to clarify changes in the classification of enteroviruses, provide information about recent disease outbreaks, and to summarize progress toward the treatment and prevention of these infections.201626709690
formononetin inhibits enterovirus 71 replication by regulating cox- 2/pge₂ expression.the activation of erk, p38 and jnk signal cascade in host cells has been demonstrated to up-regulate of enterovirus 71 (ev71)-induced cyclooxygenase-2 (cox-2)/ prostaglandins e2 (pge₂) expression which is essential for viral replication. so, we want to know whether a compound can inhibit ev71 infection by suppressing cox-2/pge₂ expression.201525890183
the antiviral effect of 7-hydroxyisoflavone against enterovirus 71 in vitro.enterovirus 71 (ev71) is the major causative agent of hand foot and mouth disease. and ev71 causes epidemics worldwide, particularly in the asia-pacific region. unfortunately, currently there is no approved vaccine or antiviral drug for ev71-induced disease prevention and therapy. in screening for anti-ev71 candidates, we found that 7-hydroxyisoflavone was active against ev71. 7-hydroxyisoflavone exhibited strong antiviral activity against three different ev71 strains. the 50% inhibitory concent ...201323464760
synthesis of pyrazine-1,3-thiazine hybrid analogues as antiviral agent against hiv-1, influenza a (h1n1), enterovirus 71 (ev71), and coxsackievirus b3 (cvb3).a novel series of pyrazine-1,3-thiazine hybrid conjugates were synthesized in excellent yield. these derivatives were subsequently tested against human immunodeficiency virus (hiv-1); hemagglutinin type 1 and neuraminidase type 1-'influenza' a (h1n1) virus; enterovirus 71 (ev71); and coxsackievirus b3. the effect of these conjugates on the key enzymes responsible for the progression of these viral infections was also illustrated via enzyme-based assay, such as hiv-1 reverse transcriptase (rt) an ...201627062664
synergistic antiviral activity of gemcitabine and ribavirin against enteroviruses.enteroviruses are major causative agents of various human diseases, and some of them are currently considered to be an enormous threat to public health. however, no effective therapy is currently available for the treatment of these infections. we identified gemcitabine, a nucleoside-analog drug used for cancer treatment, from a screen of bioactive chemicals as a novel inhibitor of coxsackievirus b3 (cvb3) and enterovirus 71 (ev71). gemcitabine potently inhibited the proliferation of cvb3 and ev ...201526526589
simultaneous point-of-care detection of enterovirus 71 and coxsackievirus b3.human enterovirus 71 (ev71) is one of the pathogens that causes hand, foot, and mouth disease (hfmd), which generally leads to neurological diseases and fatal complications among children. since the early clinical symptoms from ev71 infection are very similar to those from coxsackievirus b3 (cvb3) infection, a robust and sensitive detection method that can be used to distinguish ev71 and cvb3 is urgently needed for prompting medical treatment of related diseases. herein, based on immunomagnetic ...201526461918
the role of micrornas in enteroviral infections.the genus enterovirus, a member of the picornavirus family, are rna viruses that can cause poliomyelitis, hand-food-mouth disease, viral meningitis or meningoencephalitis, viral myocarditis and so on. micrornas are a class of highly conserved, small noncoding rnas recognized as important regulators of gene expression. recent studies found that micrornas play a significant role in the infection of enterovirus, such as enterovirus 71, coxsackievirus b3 and other enterovirus. enteroviral infection ...201526342975
antiviral activity of chrysin derivatives against coxsackievirus b3 in vitro and in vivo.chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (ev71) by suppressing viral 3c protease (3c(pro)) activity. in the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus b3 (cvb3), which belongs to the same genus (enterovirus) as ev71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. we found that chrysin showed antiviral activity against cvb3 at 10 μm, but exhibited mild ...201526336587
exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.the enterovirus genus of the picornaviridae is represented by several viral pathogens that are associated with human disease, namely poliovirus 1, enterovirus 71 and rhinoviruses. enterovirus 71 has been associated with encephalitis, while rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of rhinovirus replication.201526071135
the rna template channel of the rna-dependent rna polymerase as a target for development of antiviral therapy of multiple genera within a virus family.the genus enterovirus of the family picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. the viral rna-dependent rna polymerase is an attractive target for antiviral therapy. nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. most non-nucleoside inhibitors (nnis) target surface cavities, which are structurally more flexible than the nucleoti ...201525799064
antiviral activity of ginsenosides against coxsackievirus b3, enterovirus 71, and human rhinovirus 3.ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. in this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (pt) type: re, rf, and rg2; protopanaxadiol (pd) type: rb1, rb2, rc, and rd)] against coxsackievirus b3 (cvb3), enterovirus 71 (ev71), and human rhinovirus 3 (hrv3).201425378991
establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.the aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and imm ...201525263613
auf1 is recruited to the stress granules induced by coxsackievirus b3.stress granules (sgs) are cytoplasmic granules that are formed in cells when stress occurs. in this study, we found that sgs formed in cells infected with coxsackievirus b3 (cvb3), evidenced with the co-localization of some accepted sg markers in the viral infection-induced granules. we further discovered that adenosine-uridine (au)-rich element rna binding factor 1 (auf1), which can bind to mrnas and regulate their translation, was recruited to the sgs in response to high dose of cvb3 by detect ...201425148713
coxsackievirus cloverleaf rna containing a 5' triphosphate triggers an antiviral response via rig-i activation.upon viral infections, pattern recognition receptors (prrs) recognize pathogen-associated molecular patterns (pamps) and stimulate an antiviral state associated with the production of type i interferons (ifns) and inflammatory markers. type i ifns play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. although pegylated ifns have been used to treat hepatitis b and c virus infections for de ...201424759703
binding of glutathione to enterovirus capsids is essential for virion morphogenesis.enteroviruses (family of the picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. we report the discovery of tp219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. we show that tp219 binds directly glutathione (gsh), thereby r ...201424722756
hepatic damage caused by coxsackievirus b3 is dependent on age-related tissue tropisms associated with the coxsackievirus-adenovirus receptor.coxsackievirus b (cvb) and enterovirus 71 (ev71) are important causes of severe enteroviral diseases in neonates or young children in taiwan. cvb can cause fulminant hepatitis, myocarditis or meningoencephalitis. this study was designed to explore the role of coxsackievirus-adenovirus receptor (car) in the pathogenesis of cvb3-infected hepatocytes via in vitro and mice studies. cvb3 (cvb3/2630) was isolated from liver tissue of a neonate with fulminant hepatitis. cell lines a549, hela, hep2 and ...201323620416
simultaneous determination of human enterovirus 71 and coxsackievirus b3 by dual-color quantum dots and homogeneous immunoassay.human enterovirus 71 (ev71) and coxsackievirus b3 (cvb3) have high risks for morbidity and mortality. a virus quantitation immunoassay has been proposed by employing two colored quantum dots (qds), antibodies of the virus, and graphene oxide (go). the qds are streptavidin-conjugated quantum dots (sa-qds), and the antibodies are biotinylated antibodies. biotinylated ev71 antibody (ab1) was associated with 525 nm green colored sa-qds via biotin-streptavidin interaction forming qds-ab1, whereas bio ...201222390751
yakammaoto inhibits enterovirus 71 infection by reducing viral attachment, internalization, replication, and translation.enterovirus 71 (ev71) can cause central nervous system infections with mortality and neurologic sequelae. at present, there is no effective therapeutic modality for ev71 infection. the infection is more common in families with poor socioeconomic status. therefore, finding a readily available, cost-effective therapeutic modality would be very helpful to these socioeconomically disadvantaged families. yakammaoto is a cheap and readily available traditional prescription that is proven to have antiv ...201526043408
conformational plasticity of the 2a proteinase from enterovirus 71.the 2a proteinase (2a(pro)) is an enterovirally encoded cysteine protease that plays essential roles in both the processing of viral precursor polyprotein and the hijacking of host cell translation and other processes in the virus life cycle. crystallographic studies of 2a(pro) from enterovirus 71 (ev71) and its interaction with the substrate are reported here. ev71 2a(pro) was comprised of an n-terminal domain of a four-stranded antiparallel β sheet and a c-terminal domain of a six-stranded ant ...201323616646
antigenic diversity of enteroviruses associated with nonpolio acute flaccid paralysis, india, 2007-2009.because of the broadened acute flacid paralysis (afp) definition and enhanced surveillance, many nonpolio afp (np-afp) cases have been reported in india since 2005. to determine the spectrum of nonpolio enterovirus (npev) serotypes associated with np-afp from polio-endemic and -free regions, we studied antigenic diversity of afp-associated npevs. of fecal specimens from 2,786 children with np-afp in 1 polio-endemic and 2 polio-free states, 823 (29.5%) were positive for npevs in rd cells, of whic ...201223092622
[outbreak of acute enterovirus intestinal infection in sakhalin region in august 2010].the investigation of cases of acute intestinal infections in the sakhalin region of russia in august, 2010 is described. epidemiological and molecular biological studies were conducted. after initial pcr screening and determining the nucleotide sequences of the positive samples the following enteroviruses were found: coxsackie a2 - 42 samples (45%), coxsackie a4--31 sample (34%), enterovirus 71--6 samples (6,5%), coxsackievirus b5--6 samples (6,5%), coxsackie b3--4 samples (4%) and coxsackie b1- ...201222642180
enhanced enterovirus 71 virus-like particle yield from a new baculovirus design.enterovirus 71 (ev71) is responsible for the outbreaks of hand-foot-and-mouth disease in the asia-pacific region. to produce the virus-like particle (vlp) vaccine, we previously constructed recombinant baculoviruses to co-express ev71 p1 polypeptide and 3cd protease using the bac-to-bac(®) vector system. the recombinant baculoviruses resulted in p1 cleavage by 3cd and subsequent vlp assembly in infected insect cells, but caused either low vlp yield or excessive vlp degradation. to tackle the pro ...201525997678
evaluation of a viral microarray based on simultaneous extraction and amplification of viral nucleotide acid for detecting human herpesviruses and enteroviruses.in this study, a viral microarray based assay was developed to detect the human herpesviruses and enteroviruses associated with central nervous system infections, including herpes simplex virus type 1, type 2 (hsv1 and hsv2), epstein-barr virus (ebv), cytomegalovirus (cmv), enterovirus 71 (ev71), coxsackievirus a 16 (ca16) and b 5(cb5). the dna polymerase gene of human herpesviruses and 5'-untranslated region of enteroviruses were selected as the targets to design primers and probes. human herpe ...201525774509
modulation of antiviral immunity by heme oxygenase-1.heme oxygenase-1 (ho-1) is a stress-inducible, anti-inflammatory, and cytoprotective enzyme expressed in most cell types in the organism. under several stress stimuli, ho-1 expression and activity is up-regulated to catalyze the rate-limiting enzymatic step of heme degradation into carbon monoxide, free iron, and biliverdin. besides its effects on cell metabolism, ho-1 is also capable of modulating host innate and adaptive immune responses in response to sepsis, transplantation, and autoimmunity ...201728082120
functional assessment and structural basis of antibody binding to human papillomavirus capsid.persistent high-risk human papillomavirus (hpv) infection is linked to cervical cancer. two prophylactic virus-like particle (vlp)-based vaccines have been marketed globally for nearly a decade. here, we review the hpv pseudovirion (psv)-based assays for the functional assessment of the hpv neutralizing antibodies and the structural basis for these clinically relevant epitopes. the psv-based neutralization assay was developed to evaluate the efficacy of neutralization antibodies in sera elicited ...201626676802
rapid next-generation sequencing of dengue, ev-a71 and rsv-a viruses.accurate characterisation of viral strains constitutes a crucial objective for the management of modern virus collections. next-generation sequencing (ngs) provides technical solution for fast and cost-effective full genome sequencing. here, we report protocols for rapid full-genome characterisation of rna viruses of medical importance: dengue virus, enterovirus a71 and respiratory syncytial virus a, based on a specific amplification step followed by ngs-sequencing. a subset of full-length genom ...201526376168
antiviral activity of lanatoside c against dengue virus infection.dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. in response to the urgent need for the development of an effective antiviral for dengue virus, the us drug collection library was screened in this study to identify compounds with anti-dengue activities. lanatoside c, an fda approved cardiac glycoside was identified as a candidate anti-dengue compoun ...201425251726
emerging viral infections.this review highlights research and development in the field of emerging viral causes of encephalitis over the past year.201323591683
enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner.enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. however, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium. we found that enteroids were susceptible to infection by diverse enteroviruses, including echovirus 11 (e11), coxsackiev ...201728137842
3c protease of enterovirus 68: structure-based design of michael acceptor inhibitors and their broad-spectrum antiviral effects against picornaviruses.we have determined the cleavage specificity and the crystal structure of the 3c protease of enterovirus 68 (ev68 3c(pro)). the protease exhibits a typical chymotrypsin fold with a cys...his...glu catalytic triad; its three-dimensional structure is closely related to that of the 3c(pro) of rhinovirus 2, as well as to that of poliovirus. the phylogenetic position of the ev68 3c(pro) between the corresponding enzymes of rhinoviruses on the one hand and classical enteroviruses on the other prompted ...201323388726
copi is required for enterovirus 71 replication.enterovirus 71 (ev71), a member of the picornaviridae family, is found in asian countries where it causes a wide range of human diseases. no effective therapy is available for the treatment of these infections. picornaviruses undergo rna replication in association with membranes of infected cells. copi and copii have been shown to be involved in the formation of picornavirus-induced vesicles. replication of several picornaviruses, including poliovirus and echovirus 11 (ev11), is dependent on cop ...201222662263
direct identification of enteroviruses in cerebrospinal fluid of patients with suspected meningitis by nested pcr amplification.enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. in the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. we developed rt-nested pcr amplification of the genomic region coding viral structural protein vp1 for direct identification ...201626751470
seroepidemiological and phylogenetic characterisation of neurotropic enteroviruses in ireland, 2005-2014.enteroviruses (evs) are associated with a broad spectrum of clinical presentation, including aseptic meningitis (am), encephalitis, hand, foot and mouth disease, acute flaccid paralysis and acute flaccid myelitis. epidemics occur sporadically and are associated with increased cases of am in children. the present study describes the seroepidemiological analysis of circulating evs in ireland from 2005-2014 and phylogenetic characterisation of echovirus 30 (e-30), enterovirus a71 (ev-a71) and enter ...201728071799
predominance of enterovirus b and echovirus 30 as cause of viral meningitis in a uk population.enteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. with reports of unusually severe neurological disease in some patients infected with enterovirus d68 in north america, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this uk midlands population, a retrospective regional surveillance study was performed.201627367546
genetic characterization of ev71 isolates from 2004 to 2010 reveals predominance and persistent circulation of the newly proposed genotype d and recent emergence of a distinct lineage of subgenotype c2 in hong kong.enterovirus 71 (ev71) is a common etiological agent of hand, foot and mouth disease (hfmd) in children. ev71 epidemics have been reported in hong kong in recent years, and yet the genetic information of ev71 strains circulating in our locality is limited. the objective of this study was to investigate the genetic evolution of these ev71 isolates in hong kong over a 7-year period.201323822185
induction and suppression of innate antiviral responses by picornaviruses.the family picornaviridae comprises of small, non-enveloped, positive-strand rna viruses and contains many human and animal pathogens including enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus 71 and rhinovirus), cardioviruses (e.g. encephalomyocarditis virus), hepatitis a virus and foot-and-mouth disease virus. picornavirus infections activate a cytosolic rna sensor, mda5, which in turn, induces a type i interferon response, a crucial component of antiviral immunity. moreover, picorn ...201425086453
quinacrine impairs enterovirus 71 rna replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.since the 1980s, epidemics of enterovirus 71 (ev71) and other enteroviruses have occurred in asian countries and regions, causing a wide range of human diseases. no effective therapy is available for the treatment of these infections. internal ribosome entry sites (iress) are indispensable for the initiation of translation in enteroviruses. several cellular factors, as well as the ribosome, are recruited to the conserved ires during this process. quinacrine intercalates into the rna architecture ...201323301007
encephalomyocarditis virus viroporin 2b activates nlrp3 inflammasome.nod-like receptors (nlrs) comprise a large family of intracellular pattern- recognition receptors. members of the nlr family assemble into large multiprotein complexes, termed the inflammasomes. the nlr family, pyrin domain-containing 3 (nlrp3) is triggered by a diverse set of molecules and signals, and forms the nlrp3 inflammasome. recent studies have indicated that both dna and rna viruses stimulate the nlrp3 inflammasome, leading to the secretion of interleukin 1 beta (il-1β) and il-18 follow ...201222916014
pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.it has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. this study demonstrated that administration of heat-killed enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. the influenza-mediated morbidity and lung inflammation in e. faecalis-treated mice decreased significantly compared with those of the control mice. furthermore, we found that the protection is associated wit ...201727072606
regulation of enterovirus 2a protease-associated viral ires activities by the cell's erk signaling cascade: implicating erk as an efficiently antiviral target.in a previous study the erk1/2 pathway was found to be crucially involved in positive regulation of the enterovirus a 71(ev-a71) ires (vires), thereby contributing to the efficient replication of an important human enterovirus causing death in young children (<5yrs) worldwide. this study focuses on unraveling more about the detailed mechanism of erk's involvement in this regulation of vires. through the use of sirnas and specifically pharmacological inhibitor u0126, the erk cascade was shown to ...201728351508
suramin interacts with the positively charged region surrounding the 5-fold axis of the ev-a71 capsid and inhibits multiple enterovirus a.suramin was previously shown to bind to the ev-a71 capsid through its naphthalenetrisulfonic acid groups, thereby reducing virus-cell binding and inhibiting viral replication. here, we identify vp1-145 as the critical amino acid that accounts for the differential sensitivity of eva-71 viruses to suramin. a single q or g to e substitution at vp1-145 results in an approximately 30-fold shift of ic50 or ic90 values reproducing the inhibition profile observed with field isolates expressing either th ...201728218309
erratum to: antiviral activity of lactobacillus reuteri protectis against coxsackievirus a and enterovirus 71 infection in human skeletal muscle and colon cell lines. 201627855715
inhibition of enterovirus vp4 myristoylation is a potential antiviral strategy for hand, foot and mouth disease.the hand, foot and mouth disease (hfmd) can result from infections by a plethora of human enteroviruses of the species enterovirus a and b. these infections are highly contagious, resulting in regular outbreaks especially in the asia-pacific region in the recent decade. although this disease is generally a childhood affliction which manifests as a mild, febrile illness accompanied by the vesicles on the hands, feet and mouth, permanent morbidity or even fatality can result from severe forms of t ...201627520386
antiviral activity of lactobacillus reuteri protectis against coxsackievirus a and enterovirus 71 infection in human skeletal muscle and colon cell lines.recurrence of hand, foot and mouth disease (hfmd) pandemics continues to threaten public health. despite increasing awareness and efforts, effective vaccine and drug treatment have yet to be available. probiotics have gained recognition in the field of healthcare worldwide, and have been extensively prescribed to babies and young children to relieve gastrointestinal (gi) disturbances and diseases, associated or not with microbial infections. since the faecal-oral axis represents the major route ...201627341804
neurologic manifestations of enterovirus 71 infection in korea.enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. here, we aimed to describe the clinical features, magnetic resonance imaging (mri) findings, and cerebrospinal fluid (csf) profiles of patients presenting with neurologic complications of enterovirus 71 infection. we retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infectio ...201627051240
ev71 vaccine, a new tool to control outbreaks of hand, foot and mouth disease (hfmd).on december 3rd 2015, the china food and drug administration (cfda) approved the first inactivated enterovirus 71 (ev71) whole virus vaccine for preventing severe hand, foot and mouth disease (hfmd). as one of the few preventive vaccines for children's infectious diseases generated by the developing countries in recent years, ev71 vaccine is a blessing to children's health in china and worldwide. however, there are still a few challenges facing the worldwide use of ev71 vaccine, including the ap ...201626732723
mapping enterovirus a71 antigenic determinants from viral evolution.human enterovirus a71 (ev-a71) belongs to the enterovirus a species in the picornaviridae family. several vaccines against ev-a71, a disease causing severe neurological complications or even death, are currently under development and being tested in clinical trials, and preventative vaccination programs are expected to start soon. to characterize the potential for antigenic change of ev-a71, we compared the sequences of two antigenically diverse genotype b4 and b5 strains of ev-a71 and identifie ...201526339057
enterovirus a71 meningoencephalitis outbreak, rostov-on-don, russia, 2013.seventy-eight cases of enterovirus infection, including 25 neuroinfections, occurred in rostov-on-don, russia, during may-june 2013. the outbreak was caused by an enterovirus a type 71 (ev-a71) subgenotype c4 lineage that spread to neighboring countries from china ≈3 years earlier. enterovirus associated neuroinfection may emerge in areas with a preceding background circulation of ev-a71 with apparently asymptomatic infection.201526196217
coxsackievirus a 16 infection does not interfere with the specific immune response induced by an enterovirus 71 inactivated vaccine in rhesus monkeys.hand, foot and mouth disease is usually caused by enterovirus 71 (ev71) and coxsackievirus a 16 (ca16), which are members of the picornaviridae family. in the present study, the characteristics of the immune response induced by an ev71 inactivated vaccine (made from human diploid cells) were explored in the presence of ca16 infection, based on the previously established neonatal rhesus monkey model. the typical clinical manifestations, including body temperature, viral viremia and virus shedding ...201424958699
[serotype distribution of non-polio enterovirus in patients with acute flaccid paralysis during 2011-2012 in hebei province, china].this study aims to investigate the serotype distribution of non-polio enterovirus (npev) isolated from patients with acute flaccid paralysis (afp) during 2011-2012 in hebei province, china and to analyze the relationship between these viruses and afp. npev strains were isolated from the stool specimens from afp cases in hebei using human rhabdomyosarcoma cells (rd) and the mouse cell line expressing the gene for the human cellular receptor for poliovirus (l20b) according to the who requirements. ...201424772895
development of loop-mediated isothermal amplification (lamp) for universal detection of enteroviruses.enteroviruses are found in most environments and cause several diseases in humans. loop-mediated isothermal amplification (lamp) was adapted and evaluated for the rapid detection of enteroviruses. based on the highly conserved 5' untranslated region (5'-utr) of the human enteroviruses (hevs), particularly human enterovirus a (hev-a) and hev-b, a set of universal primers was designed. the lamp amplification was carried out under isothermal conditions at 61 °c, depending on the template concentrat ...201424426171
recombination strategies and evolutionary dynamics of the human enterovirus a global gene pool.we analysed natural recombination in 79 human enterovirus a strains representing 13 serotypes by sequencing of vp1, 2c and 3d genome regions. the half-life of a non-recombinant tree node in coxsackieviruses 2, 4 and 10 was only 3.5 years, and never more than 9 years. all coxsackieviruses that differed by more than 7 % of the nucleotide sequence in any genome region were recombinants relative to each other. enterovirus 71 (ev71), on the contrary, displayed remarkable genetic stability. three majo ...201424425417
[observation on virus shedding periods of enterovirus-71 and coxsackievirus a 16 monitored by nucleic acids determination in stool samples of children with hand, foot and mouth disease].to observe the duration of enterovirus-71 (ev71) and coxsackievirus a 16 (coxa16) viral shedding in stool samples of children with hand, foot and mouth disease (hfmd) infected with ev71 and coxa16 and to explore the relationship between the duration of intestinal virus shedding and the severity of illness of children with hfmd.201324406235
tonsillar crypt epithelium is an important extra-central nervous system site for viral replication in ev71 encephalomyelitis.enterovirus 71 (ev71; family picornaviridae, species human enterovirus a) usually causes hand, foot, and mouth disease, which may rarely be complicated by fatal encephalomyelitis. we investigated extra-central nervous system (extra-cns) tissues capable of supporting ev71 infection and replication, and have correlated tissue infection with expression of putative viral entry receptors, scavenger receptor b2 (scarb2), and p-selectin glycoprotein ligand-1 (psgl-1). formalin-fixed, paraffin-embedded ...201424378407
enterovirus genotypes causing hand foot and mouth disease in shanghai, china: a molecular epidemiological analysis.a rapid expansion of hand, foot, and mouth disease (hfmd) outbreaks has occurred and caused deaths in china in recent years, but little is known about the other etiologic agents except enterovirus 71 (ev71) and coxsackievirus a 16 (ca16). the objective of this study is to determine the genotype compositions of enterovirus causing hfmd in shanghai and identify any associations between enterovirus types and clinical manifestations.201324148902
establishment of cell lines with increased susceptibility to ev71/ca16 by stable overexpression of scarb2.human enterovirus type 71 (ev71) and coxsackievirus a group type 16 (ca16) belong to human enterovirus species a of the family picornaviridae. these viruses are recognized as the major pathogens responsible for epidemics of hand-foot-mouth disease (hfmd), which presents with fever and vesicular eruptions of palms, soles of the feet or mouth. human scavenger receptor class b, member 2 (scarb2) has been identified as the receptor for both ev71 and ca16, as overexpression of scarb2 in cells can enh ...201323919614
seroepidemiology of human enterovirus71 and coxsackievirusa16 among children in guangdong province, china.hand, foot and mouth disease (hfmd) is a common pediatric illness. mainly induced by the enterovirus 71 and coxsackievirus a 16 infections, the frequently occurred hfmd outbreaks have become a serious public health problem in southeast asia. currently,only a few studies have investigated the human immunity to hfmd in china. in this study, we conducted a cohort study in guangdong province, china.201323855481
risk factors for neurologic complications of hand, foot and mouth disease in the republic of korea, 2009.in 2009, the first outbreak of hand, foot and mouth disease (hfmd) or herpangina (hp) caused by enterovirus 71 occurred in the republic of korea. this study inquired into risk factors associated with complications of hfmd or hp. a retrospective medical records review was conducted on hfmd or hp patients for whom etiologic viruses had been verified in 2009. one hundred sixty-eight patients were examined for this investigation. eighty patients were without complications while 88 were accompanied b ...201323341722
characterization of a novel monoclonal antibody reactive against the n-terminal region of enterovirus 71 vp1 capsid protein.hand, foot and mouth disease (hfmd) is a viral infectious disease caused by human enterovirus a, particularly enterovirus 71 (ev71) and coxsackievirus 16 (ca16) serotypes, with ev71 infection associated with severe neurological complications and mortality. lots of attention has been placed on elucidating viral epitopes, which is useful for ev71 viral research. in this study, a murine monoclonal antibody (mab 4) specific for ev71 was generated and mapped to target the n-terminal region of vp1 cap ...201323219932
seroepidemiology of human enterovirus71 and coxsackievirusa16 in jiangsu province, china.the major etiology of hand, foot and mouth disease (hfmd) is infection with human enterovirus a (hev-a). among subtypes of hev-a, coxsackievirusa16 (coxa16) and enterovirus 71 (ev71) are major causes for recurrent hfmd among infants and children in jiangsu province, mainland china. here, we analyzed maternal antibodies between prenatal women and their neonates, to determine age-specific seroprevalence of human ev71 and coxa16 infections in infants and children aged 0 to 15 years. the results may ...201223102275
challenges to licensure of enterovirus 71 vaccines.human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (ev71), which frequently involve neurological complications. ev71 vaccines are being evaluated in humans. however, several challenges to licensure of ev71 vaccines need to be addressed. firstly, ev71 and coxsackievirus a (ca) are frequently found to co-circulate and cause hand-foot-mouth disease (hfmd). a polyvalent vaccine that can provide protection against ev71 and prevalent ca are desirable. seco ...201222953003
lithium chloride inhibits early stages of foot-and-mouth disease virus (fmdv) replication in vitro.foot-and-mouth disease virus (fmdv) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. fmd vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. however, the use of fmd vaccines to protect early infection is limited. therefore, the alternative strategy of applying antiviral agents is required to control the spread of fmdv in outbreak situations. as previously reported, licl ha ...201728390158
epidemics and aetiology of hand, foot and mouth disease in xiamen, china, from 2008 to 2015.over the past 8 years, human enteroviruses (hevs) have caused 27 227 cases of hand, foot and mouth disease (hfmd) in xiamen, including 99 severe cases and six deaths. we aimed to explore the molecular epidemiology of hfmd in xiamen to inform the development of diagnostic assays, vaccines and other interventions. from january 2009 to september 2015, 5866 samples from sentinel hospitals were tested using nested reverse transcription pcr that targeted the hev 5' untranslated region and viral protei ...201728367766
outbreak of brainstem encephalitis associated with enterovirus-a71 in catalonia, spain (2016): a clinical observational study in a children's reference centre in catalonia.to describe the characteristics of an outbreak of brainstem encephalitis and encephalomyelitis related to enterovirus (ev) infection in catalonia (spain), a setting where these manifestations were uncommon.201728344164
enterovirus 71 neutralizing antibodies seroepidemiological research among children in guangzhou, china between 2014 and 2015: a cross-sectional study.a hand-foot-mouth disease outbreak occurred in 2014 around guangdong. the purpose of this study was investigating the status and susceptibility of infectious neutralizing antibodies to enterovirus 71 among children so as to provide scientific evidence for the population immunity level of hand-foot-mouth disease and prepare for enterovirus 71 vaccination implementation. serum specimens were collected from children in communities from january 2014 to march 2015 in guangzhou. a total of 197 serum s ...201728335535
efficacy and safety evaluation of a chlorine dioxide solution.in this study, a chlorine dioxide solution (uc-1) composed of chlorine dioxide was produced using an electrolytic method and subsequently purified using a membrane. uc-1 was determined to contain 2000 ppm of gaseous chlorine dioxide in water. the efficacy and safety of uc-1 were evaluated. the antimicrobial activity was more than 98.2% reduction when uc-1 concentrations were 5 and 20 ppm for bacteria and fungi, respectively. the half maximal inhibitory concentrations (ic50) of h1n1, influenza vi ...201728327506
squamous epitheliotropism of enterovirus a71 in human epidermis and oral mucosa.hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by enterovirus a71 (genus: enterovirus, family: picornaviridae). typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of enterovirus a71 in human skin and oral mucosa are unknown. in enterovirus a71-infect ...201728322333
the golgi protein acbd3 facilitates enterovirus 71 replication by interacting with 3a.enterovirus 71 (ev71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. although ev71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. by screening human cdna library, we uncover that the golgi resident protein acyl-coenzyme a binding domain-containing 3 (acbd3) serves as a target of the 3a protein of ev71. this interaction occurs in cells expressing 3a or i ...201728303920
best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review.hand, foot, and mouth disease continues to cause seasonal epidemics in the asia-pacific region. since the current enterovirus 71 vaccines do not provide cross-protection for all enterovirus species that cause hand, foot, and mouth disease, there is an urgent need to identify appropriate detection tools and best practice to prevent its transmission and to effectively control its outbreaks. this systematic review aimed to identify characteristics of outbreak and assess the impact and effectiveness ...201728302925
a novel benzo-heterocyclic amine derivative n30 inhibits influenza virus replication by depression of inosine-5'-monophospate dehydrogenase activity.influenza virus is still a huge threat to the world-wide public health. host inosine-5'- monophosphate dehydrogenase (impdh) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative n30, which was designed to inhibit impdh.201728298229
paediatric active enhanced disease surveillance inaugural annual report, 2014.the paediatric active enhanced disease surveillance (paeds) network is a hospital-based active surveillance system employing prospective case ascertainment of selected uncommon vaccine preventable diseases and potential adverse events following immunisation (aefi). paeds enhances other australian surveillance systems by providing prospective detailed clinical and laboratory data for the same child.201628278415
the uncoupling of catalysis and translocation in the viral rna-dependent rna polymerase.the nucleotide addition cycle of nucleic acid polymerases includes two major events: the pre-chemistry active site closure leading to the addition of one nucleotide to the product chain; the post-chemistry translocation step moving the polymerase active site one position downstream on its template. in viral rna-dependent rna polymerases (rdrps), structural and biochemical evidences suggest that these two events are not tightly coupled, unlike the situation observed in a-family polymerases such a ...201728277928
enhancing enterovirus a71 vaccine production yield by microcarrier profusion bioreactor culture.hand, foot and mouth diseases (hfmd) are mainly caused by enterovirus a71 (ev-a71) infections. clinical trials in asia conducted with formalin-inactivated ev-a71 vaccine candidates produced from serum-free vero cell culture using either roller bottle or cell factory technology, are found to be safe and highly efficacious. to increase vaccine yields and reduce the production costs, the bioprocess improvement for ev-a71 vaccine manufacturing is currently being investigated. the parameters that cou ...201728274636
report from the world health organization's third product development for vaccines advisory committee (pdvac) meeting, geneva, 8-10th june 2016.the third meeting of who's product development for vaccines advisory committee (pdvac) was held in june 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase iii trials of a ...201728262332
correction: enterovirus 71 protease 2apro targets mavs to inhibit anti-viral type i interferon responses.[this corrects the article doi: 10.1371/journal.ppat.1003231.].201728253362
microrna screening identifies mir-134 as a regulator of poliovirus and enterovirus 71 infection.micrornas (mirnas) regulate virus replication through multiple mechanisms. poliovirus causes a highly debilitating disease and though global efforts to eradicate polio have sharply decreased polio incidence, unfortunately three countries (afghanistan, nigeria and pakistan) remain polio-endemic. we hypothesize that understanding the host factors involved in polio replication will identify novel prophylactic and therapeutic targets against polio and related viruses. in this data set, employing gen ...201728248924
recombinant heat shock protein 78 enhances enterovirus 71 propagation in vero cells and is induced in sk-n-sh cells during the infection.enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease (hfmd), which mainly occurs in children. children with ev71 infection can develop severe neurological diseases. heat shock protein 78 (hsp78) facilitates proper protein folding during viral propagation and is induced during virus infection. nevertheless, the role that hsp78 plays during ev71 infection is still unclear. in this study, recombinant hsp78 protein was expressed in a prokaryotic expression syste ...201728236071
flos farfarae inhibits enterovirus 71-induced cell injury by preventing viral replication and structural protein expression.enterovirus 71 (ev71) infection can cause airway symptoms, brainstem encephalitis, neurogenic shock, and neurogenic pulmonary edema with high morbidity and mortality. there is no proven therapeutic modality. flos farfarae is the dried flower bud of tussilago farfara l. that has been used to manage airway illnesses for thousands of years. it has neuro-protective activity and has been used to manage neuro-inflammatory diseases. however, it is unknown whether flos farfarae has activity against ev71 ...201728231741
human enterovirus 68 interferes with the host cell cycle to facilitate viral production.enterovirus d68 (ev-d68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the united states and other countries. little is known about the relationship between ev-d68 virus and host cells. in this study, we assessed the effect of the host cell cycle on ev-d68 viral production, as well as the ability of ev-d68 to manipulate host cell cycle progression. the results suggest that synchronization in g0/g1 phase, but not s phase, promotes viral production, ...201728229049
human enterovirus 71 protein interaction network prompts antiviral drug repositioning.as a predominant cause of human hand, foot, and mouth disease, enterovirus 71 (ev71) infection may lead to serious diseases and result in severe consequences that threaten public health and cause widespread panic. although the systematic identification of physical interactions between viral proteins and host proteins provides initial information for the recognition of the cellular mechanism involved in viral infection and the development of new therapies, ev71-host protein interactions have not ...201728220872
a novel enterovirus 71 (ev71) virulence determinant: the 69th residue of 3c protease modulates pathogenicity.human enterovirus type 71 (ev71), the major causative agent of hand-foot-and-mouth disease, has been known to cause fatal neurological complications. unfortunately, the reason for neurological complications that have been seen in fatal cases of the disease and the relationship between ev71 virulence and viral genetic sequences remains largely undefined. the 3c protease (3c(pro)) of ev71 plays an irreplaceable role in segmenting the precursor polyprotein during viral replication, and intervening ...201728217559
[analysis of the clinical features of infections caused by enterovirus a71 (ev-a71) in balearic islands]. 201728215717
rapid detection and quantification of enterovirus 71 by a portable surface plasmon resonance biosensor.this study presents the first report on a label-free detection and rapid quantification method for human enterovirus 71 (ev71) using a portable surface plasmon resonance (spr) system. the spr sensor instrument was configured to run on low power in a miniaturized platform to improve the device portability for a wider application both in laboratories and in the field. a color tunable organic light emitting diode in red spectrum was attached on a trapezoidal prism for the disposable light source mo ...201728214745
clinical manifestations of severe enterovirus 71 infection and early assessment in a southern china population.enterovirus 71 (ev-a71) shows a potential of rapid death, but the natural history of the infection is poorly known. this study aimed to examine the natural history of ev-a71 infection.201728212620
association of toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in chinese children.enterovirus 71 (ev71) infection has become one of the major threats to children globally in recent years. toll-like receptor 3 (tlr3) plays an essential role in host defense against ev71 infection. this study was designed to assess the possible association between the tlr3c.1377c/t polymorphism and disease severity in chinese children with ev71 infection. the tlr3c.1377c/t gene polymorphism was identified in ev71-infected patients (n = 177), including mild cases (n = 99) and severe cases (n = 78 ...201728190199
the impact of hand, foot and mouth disease control policies in singapore: a qualitative analysis of public perceptions.hand foot and mouth disease (hfmd) is a widespread pediatric disease in asia. most cases are relatively mild and caused by coxsackie viruses, but in epidemics caused by enterovirus 71, severe complications can occur. in response to the deaths of dozens of children in a 1997 outbreak (podin in bmc public health 6:180,1 abubakar in virus res 61(1):1-9,2 who in3), singapore practices childcare centre surveillance, case-isolation, and short-term closure of centres. we conducted 44 in-depth interview ...201728179628
an ultrasensitive biosensing platform employing acetylcholinesterase and gold nanoparticles.enzyme-linked immunosorbent assay (elisa) is a well-known strategy for biomarker detection with a color change, which can be seen by the naked eyes. however, the moderate sensitivity of conventional elisa limits its applications in many cases where the concentrations of biomarker are very low, such as cancer diagnosis. here we describe an ultrasensitive colorimetric assay based on acetylcholinesterase (ache)-catalyzed hydrolysis reaction, whose products trigger the aggregation of gold nanopartic ...201728150210
interferon-α and inosine pranobex-mediated inhibition of reploication of human rna viruses in vitro.interferon- a (ifn-a), produced by immune cells, exhibits pleiotropic anti- viral activity. inosine pranobex (pi), a synthetic derivative of a purine, shows direct anti- viral activity, and also acts indirectly, by activation of immune cells. the aim of this study was to evaluate an in vitro inhibition of coxackievirus a16 (cai6), enterovirus 71 (ev71) and human parainfluenza virus 4 (hpiv-4) replication by pi in combination with ifn-a.201728146624
antiviral activity of acid beta-glucosidase 1 on enterovirus 71, a causative agent of hand-foot-mouth disease.enterovirus 71 (ev71) is a causative agent of hand-foot-mouth disease (hfmd). ev71 causes fever, rash, diarrhea, and, in some cases, acute encephalopathy/encephalitis, which can be fatal. no specific treatment is currently available for ev71 infection. here, we conducted a cdna library screen and identified acid β-glucosidase 1 (gba1; also known as β-glucocerebrosidase) as an ev71 resistance factor. the anti-ev71 function of gba1 was verified by gene transduction and knockdown experiments. cerez ...201728141506
hsa-let-7c-5p augments enterovirus 71 replication through viral subversion of cell signaling in rhabdomyosarcoma cells.human enterovirus 71 (ev71) causes severe hand, foot and mouse disease, accompanied by neurological complications. during the interaction between ev71 and the host, the virus subverts host cell machinery for its own replication. however, the roles of micrornas (mirnas) in this process remain obscure.201728101327
[association of tlr3-1377c/t gene polymorphisms and expression with susceptibility to enterovirus 71 encephalitis in children].to investigate the association of gene polymorphisms of toll-like receptor 3 (tlr3)-1377c/t and expression of tlr3 with the susceptibility to enterovirus 71 (ev71) encephalitis in children.201728100320
berberine inhibits enterovirus 71 replication by downregulating the mek/erk signaling pathway and autophagy.the mek-erk signaling pathway and autophagy play an important role for enterovirus71(ev71) replication. inhibition of mek-erk signaling pathway and autophagy is shown to impair ev71 replication. berberine (bbr), an isoquinoline alkaloid isolated from berberis vulgaris l., has been reported to have ability to regulate this signaling pathway and autophagy. herein, we want to determine whether berberine can inhibit ev71 infection by downregulating the mek/erk signaling pathway and autophagy.201728081706
2-year efficacy, immunogenicity, and safety of vigoo enterovirus 71 vaccine in healthy chinese children: a randomized open-label study.this study evaluated the 2-year efficacy, immunogenicity, and safety of the vigoo enterovirus 71 (ev71) vaccine.201728077584
enterovirus 71 induces apoptosis by directly modulating the conformational activation of pro-apoptotic protein bax.enterovirus 71 (eva71), a virus of the genus enterovirus in the family picornaviridae, is one of the main causative agents of hand, foot and mouth disease in infected infants and young children. in this study, we report that cells with eva71 infection exhibit increased levels of cytochrome c release and caspase-3 activation. eva71 infection induces the conformational activation of pro-apoptotic protein bax and the subsequent formation of oligomers of bax in mitochondria. inhibitors that block ca ...201728073399
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