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preclinical safety assessment of a combined vaccine against hepatitis a virus and enterovirus 71.since 2007, hepatitis a (hav) vaccination has been a part of the national immunization program of china. recognizing enterovirus 71 (ev71) as the most important pathogen in severe hand, foot and mouth disease, an inactivated ev71 vaccine was successfully marketed in 2015. based on the concept of one vaccine preventing two diseases and owing to similarities in vaccine preparation and the overlap of the eligible population, a combination of the inactivated hav vaccine and inactivated ev71 vaccine ...202134088510
safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus a16 in rhesus monkeys.enterovirus 71 (ev-a71) and coxsackievirus a16 (cv-a16) are the two most common pathogens causing hand, foot, and mouth disease (hfmd). previously, we obtained one candidate live attenuated strain each for ev-a71 and cv-a16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine against ev-a71 and cv-a16 generated from these two candidate strains. rhesus monkeys were intramuscularly treated with a live combinationvaccine against both ev-a71 and cv-a16 or with either vaccine a ...202032159429
study of integrated protective immunity induced in rhesus macaques by the intradermal administration of a bivalent ev71-ca16 inactivated vaccine.enterovirus type 71 (ev71) and coxsackievirus a 16 (ca16) are recognized as the major pathogens responsible for human hand-foot-mouth disease. to develop a bivalent ev71-ca16 vaccine, rhesus macaques immunized with two doses of this vaccine via the intradermal route were challenged with ev71 or ca16, and their clinical symptoms, viral shedding, neutralizing antibodies, ifn-γ-specific elispots, and tissue viral load were examined longitudinally. specific immunity against ev71 and ca16 was observe ...202031982260
establishment and transcriptomic features of an immortalized hepatic cell line of the chinese tree shrew.the chinese tree shrew (tupaia belangeri chinesis) is a rising experimental animal and has been used for studying a variety of human diseases, such as metabolic and viral infectious diseases.202032880691
enterovirus type 71-immunized chicken egg yolk immunoglobulin has cross antiviral activity against coxsackievirus a16 in vitro.to exploit a cross passive immunotherapy for enterovirus-induced hand-foot-and-mouth disease (hfmd), the cross antiviral activity of a neutralizing antibody against enterovirus 71 (ev71) and coxsackievirus a16 (cva16) was investigated in vitro. white leghorn specific-pathogen-free chickens were immunized with ev71 antigens and a specific isolated immunoglobulin (igy) was prepared from the chicken egg yolk. igy was further purified and characterized by sds-page, elisa, western blotting and bidire ...201931258670
preparation and identification of chicken egg yolk immunoglobulins against human enterovirus 71 for diagnosis of hand-foot-and-mouth disease.human enterovirus 71 (ev71) is one of the major pathogens that causes hand-foot-and mouth disease, and there is an urgent need for rapid diagnosis of ev71 virus infection for early antiviral treatment. the aim of this study was to prepare chicken egg yolk immunoglobulin y (igy) for the diagnosis of enterovirus type 71 infection. the antibodies were raised by intramuscular immunization of laying hens with inactivated human ev71 and isolated from the egg yolk by multiple steps of polyethylene glyc ...201930831098
enhanced neutralizing antibody response induced by inactivated enterovirus 71 in cynomolgus monkeys.enterovirus 71 (ev71) is a major etiological agent of various public health issues, particularly in the asia-pacific region. ev71 causes hand-foot-and-mouth disease (hfmd) and is associated with serious neurological disorders in young children. a formalin-inactivated ev71 candidate vaccine (kcdc-hfmdv1-ev71) based on the c4 subgenotype was previously developed and confirmed to be a potential candidate vaccine for prevention of ev71 infection in mice. in this study, an inactivated ev71 vaccine wa ...201830278051
vp1 amino acid residue 145 of enterovirus 71 is a key residue for its receptor attachment and resistance to neutralizing antibody during cynomolgus monkey infection.enterovirus 71 (ev71) is a causative agent of hand, foot, and mouth disease and sometimes causes severe or fatal neurological complications. the amino acid at vp1-145 determines the virological characteristics of ev71. viruses with glutamic acid (e) at vp1-145 (vp1-145e) are virulent in neonatal mice and transgenic mice expressing human scavenger receptor b2, whereas those with glutamine (q) or glycine (g) are not. however, the contribution of this variation to pathogenesis in humans is not full ...201829848582
high-throughput sequencing of putative novel micrornas in rhesus monkey peripheral blood mononuclear cells following ev71 and ca16 infection.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) remain the major pathogens in hand, foot, and mouth disease (hfmd) cases, but the mechanisms of the different pathogeneses that follow ev71 and ca16 infection remain largely unknown.201830404089
establishment and characterization of an oral gerbil model for a non-mouse-adapted enterovirus 71 strain.enterovirus 71 (ev71) is one of the major pathogens causing hand, foot, and mouth disease (hfmd) with neurological and systemic complications worldwide, and it is mostly discovered in infants and young children. it is of great significance to establish suitable animal models of ev71 infection on research of distribution and pathogenesis of the virus. in this study, we established a successful infection of a non-mouse-adapted isolate of ev71 via oral route in 7-day-old mongolian gerbil (meriones ...201830030018
pulmonary edema following central nervous system lesions induced by a non- mouse-adapted ev71 strain in neonatal balb/c mice.enterovirus (ev) infection has been a serious health issue in asia-pacific region. it has been indicated that the occurrence of fatal hand foot and mouth disease (hfmd) cases following ev71 infection is mainly attributed to pulmonary edema. however, the development of pulmonary disorders after ev71 infection remains largely unknown. to establish an ev71-infected animal model and further explore the underlying association of central nervous system (cns) invasion with pulmonary edema, we isolated ...201729282065
dynamic interaction of enterovirus 71 and dendritic cells in infected neonatal rhesus macaques.enterovirus 71 (ev71) is one of the main pathogens responsible for hand, foot, and mouth disease (hfmd). infection with ev71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. based on the previous pathological study of ev71 infections in neonatal rhesus macaques, our work using this animal model and an ev71 chimera that expresses enhanced green fluorescent protein (egfp-ev71) primarily explored where ev71 localizes and prolif ...201728540257
a novel combined vaccine based on monochimeric vlp co-displaying multiple conserved epitopes against enterovirus 71 and varicella-zoster virus.chicken pox and hand, foot and mouth disease (hfmd) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. varicella-zoster virus (vzv) and enterovirus 71 (ev71), respectively, are the principal epidemic pathogens causing these two diseases. to investigate the possibility of developing a novel combined vaccine to prevent chicken pox and hfmd, we constructed three chimeric virus-like particles (vlps) (termed hbc-v/1/2, hbc-2/v/1 and hbc- ...201728408118
impact of genetic changes, pathogenicity and antigenicity on enterovirus- a71 vaccine development.enterovirus-a71 (ev-a71) is an etiological agent of the hand, foot and mouth disease (hfmd). ev-a71 infection produces high fever and ulcers in children. some ev-a71 strains produce severe infections leading to pulmonary edema and death. although the protective efficacy of the inactivated vaccine (iv) was ≥90% against mild hfmd, there was approximately 80% protection against severe hfmd. the monovalent ev-a71 iv elicits humoral immunity but lacks long-term immunogenicity. spontaneous mutations o ...201728384566
a neonatal murine model of coxsackievirus a6 infection for evaluation of antiviral and vaccine efficacy.hand, foot and mouth disease (hfmd) is a global health concern. family picornaviridae members, particularly enterovirus 71 (eva71) and coxsackievirus a16 (cva16), are the primary etiological agents of hfmd, however, a third enterovirus a species, coxsackievirusa6 (cva6), has been recently associated with epidemic outbreaks. study of the pathogenesis of cva6 infection and development of antivirals and vaccines are hindered due to the lack of appropriate animal models. we have developed and charac ...201728250116
transcriptome analysis reveals dynamic changes in coxsackievirus a16 infected hek 293t cells.coxsackievirus a16 (cva16) and enterovirus 71 (ev71) are two of the major causes of hand, foot and mouth disease (hfmd) world-wide. although many studies have focused on infection and pathogenic mechanisms, the transcriptome profile of the host cell upon cva16 infection is still largely unknown.201728198671
enterovirus 71 infection and vaccines.hand, foot and mouth disease (hfmd) is a highly contagious viral infection affecting young children during the spring to fall seasons. recently, serious outbreaks of hfmd were reported frequently in the asia-pacific region, including china and korea. the symptoms of hfmd are usually mild, comprising fever, loss of appetite, and a rash with blisters, which do not need specific treatment. however, there are uncommon neurological or cardiac complications such as meningitis and acute flaccid paralys ...201728168168
inhibition of enterovirus 71 replication by an α-hydroxy-nitrile derivative nk-1.9k.enterovirus 71 (ev71) is one of the major etiological agents of human hand-foot-and-mouth disease (hfmd) worldwide. ev71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. however, there is still no approved drugs to treat such infections. based on our previous report of a peptide-aldehyde anti-ev71 protease, we present here a highly specific α-hydroxy-nitrile derivative nk-1.9k, which inhibited the proliferation of multiple ev71 strai ...201728063993
[direct medical costs and influencing factors in severe hand, foot and mouth disease in children aged between six months and five years old].objective: to estimate the direct medical cost of severe hand, foot and mouth disease (hfmd) in patients aged less than five years. methods: a stratified sampling method was used to collect data on severe hfmd cases reported in the national hfmd surveillance database between jan 1, 2012, and dec 31, 2013. the sampling was referenced with the national aetiologic distribution of enterovirus a71 (ev-a71), coxsackievirus a16 (cv-a16) and other enteroviruses (oev) for severe hfmd cases and the includ ...201728056277
in vivo imaging with bioluminescent enterovirus 71 allows for real-time visualization of tissue tropism and viral spread.hand, foot, and mouth disease (hfmd) is a reemerging illness caused by a variety of enteroviruses. the main causative agents are enterovirus 71 (ev71), coxsackievirus a16 (cva16), and, most recently, coxsackievirus a6 (cva6). enterovirus infections can vary from asymptomatic infections to those with a mild fever and blisters on infected individuals' hands, feet, and throats to infections with severe neurological complications. viral persistence for weeks postinfection (wpi) has also been documen ...201727974562
epidemiology and etiology of hand, foot, and mouth disease in fujian province, 2008-2014.millions of cases of hand, foot, and mouth disease (hfmd) have been reported annually in mainland china since 2008. in this study, we investigated the epidemiology and etiology of an hfmd epidemic in fujian province, which is located in subtropical southeastern china. our study found similar epidemiological features of hfmd in southern areas of china, including seasonality and demographic distribution, as well as correlation between severity of illness and serotype. at least 22 serotypes of othe ...201727796546
molecular epidemiology of enterovirus and parechovirus infections according to patient age over a 4-year period in spain.the epidemiology and clinical association of enterovirus (ev) and parechovirus (hpev) infections, as well as the type-distribution-according-to-age, were determined during a 4-year study period in spain. during 2010-2013, a total of 21,832 clinical samples were screened for ev and the detection frequency was 6.5% (1,430). of the total ev-negative samples, only 1,873 samples from 2011 to 2013 were available for hpev testing. hpev was detected in 42 (2%) of them. positive samples were genotyped us ...201727505281
comparison analysis of micrornas in response to ev71 and ca16 infection in human bronchial epithelial cells by high-throughput sequencing to reveal differential infective mechanisms.hand, foot, and mouth disease (hfmd) mainly caused by enterovirus 71 (ev71) and coxsackievirus a16 (ca16) infections which presented significantly different clinical manifestations. nevertheless, the factors underlying these differences remain unclear. recently, the functions of micrornas (mirnas) in pathogen-host interactions have been highlighted. here, we performed comprehensive mirna profiling in ev71- and ca16-infected human bronchial epithelial (16hbe) cells at multiple time points using h ...201727890633
enterovirus a71 and coxsackievirus a16 show different replication kinetics in human neuronal and non-neuronal cell lines.enterovirus a71 (ev-a71) and coxsackievirus a16 (cv-a16) are closely related enteroviruses that cause hand, foot and mouth disease (hfmd) in children. serious neurological complications almost always occur in ev-a71 infection, but are rare in cv-a16 infection. based on the hypothesis that this may be because ev-a71 infects neuronal cells more easily than cv-a16, we compared virus infection, replication and spread of ev-a71 and cv-a16 in sk-n-sh cells. we found that cv-a16 invariably showed signi ...201727878462
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
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
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
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
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
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
ev71 3d protein binds with nlrp3 and enhances the assembly of inflammasome complex.activation of nlrp3 inflammasome is important for effective host defense against invading pathogen. together with apoptosis-associated speck-like protein containing card domain (asc), nlrp3 induces the cleavage of caspase-1 to facilitate the maturation of interleukin-1beta (il-1β), an important pro-inflammatory cytokine. il-1β subsequently plays critical roles in inflammatory responses by activating immune cells and inducing many secondary pro-inflammatory cytokines. although the role of nlrp3 i ...201728060938
structure-activity relationship studies on a trp dendrimer with dual activities against hiv and enterovirus a71. modifications on the amino acid.we have recently described a new class of dendrimers with tryptophan (trp) on the surface that show dual antiviral activities against hiv and ev71 enterovirus. the prototype compound of this family is a pentaerythritol derivative with 12 trps on the periphery. here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. with this aim, novel dendrimers containing different amino acids (aromatic and non-a ...201728017762
an elaborate landscape of the human antibody repertoire against enterovirus 71 infection is revealed by phage display screening and deep sequencing.enterovirus 71 (ev71) causes outbreaks of hand, foot and mouth disease (hfmd), primarily in the asia-pacific area, that are often associated with complications of severe to fatal neurological symptoms. there are currently no anti-viral therapies or vaccines available for the treatment of ev71 infection. illustrating human antibody responses neutralizing ev71 infection could potentially provide valuable information for the development of effective therapies and vaccines. here, we constructed a co ...201727929745
development of a fluorescence resonance energy transfer-based intracellular assay to identify novel enterovirus 71 antivirals.enterovirus 71 (ev71) is considered one of the most virulent pathogens in the family picornaviridae. however, there have been no effective treatments for the severe complications caused by ev71. development of new drugs against targets that are essential for viral replication often requires screening large collections of compounds, for which a high-throughput screening platform is needed. in this study, a drug-screening platform was developed based on a genetically engineered cell line that disp ...201727873071
immunoreactivity analysis of the nonstructural proteins of human enterovirus 71.human enterovirus 71 (ev-a71) is one of the main etiological agents of hand, foot, and mouth disease (hfmd), which has been prevalent mainly in the asia-pacific region in the past several decades. the nonstructural proteins of ev-a71 will be expressed significantly during viral replication in host cells after ev-a71 infection. for the determination of the antibodies response against nonstructural proteins of ev-a71, in this study, the complete 2abc, 3abc, and 3d proteins were expressed in escher ...201727870604
clinically isolated enterovirus a71 subgenogroup c4 strain with lethal pathogenicity in 14-day-old mice and the application as an ev-a71 mouse infection model.the enterovirus a71 (ev-a71) subgenogroup c4 is prevalent in china. ev-a71 causes hand, foot and mouth disease (hfmd) in children and may lead to severe neurological diseases. the development of antiviral and protective vaccines against ev-a71 is significantly hindered by the lack of suitable animal models to recapitulate human neurological symptoms. in this study, gz-cii, a highly virulent ev-a71 subgenogroup c4 strain, was isolated from hospitalized children with hfmd. intraperitoneal infectio ...201727864074
glucocorticoids prevent enterovirus 71 capsid protein vp1 induced calreticulin surface exposure by alleviating neuronal er stress.severe hand-foot-and-mouth disease (hfmd) caused by enterovirus 71 (ev71) always accompanies with inflammation and neuronal damage in the central nervous system (cns). during neuronal injuries, cell surface-exposed calreticulin (ecto-crt) is an important mediator for primary phagocytosis of viable neurons by microglia. our data confirmed that brainstem neurons underwent neuronophagia by glia in ev71-induced death cases of hfmd. ev71 capsid proteins vp1, vp2, vp3, or vp4 did not induce apoptosis ...201727848175
enterovirus 71 3c promotes apoptosis through cleavage of pinx1, a telomere binding protein.enterovirus 71 (ev71) is an emerging pathogen causing hand, foot, and mouth disease (hfmd) and fatal neurological diseases in infants and young children due to their underdeveloped immunocompetence. ev71 infection can induce cellular apoptosis through a variety of pathways, which promotes ev71 release. the viral protease 3c plays an important role in ev71-induced apoptosis. however, the molecular mechanism responsible for 3c-triggered apoptosis remains elusive. here, we found that ev71 3c direct ...201727847364
rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.human enterovirus 71 (ev71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (hfmd) in asia. currently, there are no drugs available for the prevention and treatment of hfmd. in this study, we compared the anti-ev71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from chinese herbs chinese rhubarb, artemisia carvifolia and astragalus, respectively, which have been traditionally used for the treatment and ...201727840410
time series modeling of pathogen-specific disease probabilities with subsampled data.many diseases arise due to exposure to one of multiple possible pathogens. we consider the situation in which disease counts are available over time from a study region, along with a measure of clinical disease severity, for example, mild or severe. in addition, we suppose a subset of the cases are lab tested in order to determine the pathogen responsible for disease. in such a context, we focus interest on modeling the probabilities of disease incidence given pathogen type. the time course of t ...201727378138
epidemiological and genetic analysis of hand-foot-mouth disease by enterovirus a71 in taizhou, p. r. china, between 2010 and 2013.out of a population of 1,098 enteroviruses (evs)-positive hand, foot, and mouth disease (hfmd) specimens, 352 were screened positive for ev-a71-accounting for 32.1% of all ev-positive specimens. this percentage denotes ev-a71 as the second major serotype of enteroviruse among hfmd suffers in taizhou. an epidemic outbreak of ev-a71 among hfmd children was found in taizhou in the second quarter of 2012. phylogeny analysis based on the vp1 complete sequences leads us to find a sub-clade (designated ...201727671219
n-terminal pro-b-type natriuretic peptide for the prognostic prediction of severe enterovirus 71-associated hand, foot, and mouth disease.the aim of this study was to determine whether n-terminal pro-b-type natriuretic peptide (nt-probnp) can predict impending brainstem encephalitis, pulmonary edema, pulmonary hemorrhage, cardiopulmonary failure, and death in children with severe enterovirus 71 (ev71)-associated hand, foot, and mouth disease (hfmd).201727818360
quinone/hydroquinone meroterpenoids with antitubercular and cytotoxic activities produced by the sponge-derived fungus gliomastix sp. zsds1-f7.fifteen compounds, including six quinone/hydroquinone meroterpenoids, purpurogemutantin (1), macrophorin a (2), 4'-oxomacrophorin (3), 7-deacetoxyyanuthone a (4), 2,3-hydro-deacetoxyyanuthone a (5), 22-deacetylyanuthone a (6), anicequol (7), three roquefortine derivatives, roquefortine c (8), (16s)-hydroxyroquefortine c (9), (16r)-hydroxyroquefortine c (10), dihydroresorcylide (11), nectriapyrone (12), together with three fatty acid derivatives, methyl linoleate (13), phospholipase a2 (14), meth ...201727417331
vp1 residues around the five-fold axis of enterovirus a71 mediate heparan sulfate interaction.enterovirus a71 (ev-a71) is a neurotropic enterovirus that uses heparan sulfate as an attachment receptor. the molecular determinants of ev-a71-heparan sulfate interaction are unknown. with in silico heparin docking and mutagenesis of all possible lysine residues in vp1, we identified that k162, k242 and k244 are responsible for heparin interaction and inhibition. ev-a71 mutants with k242a and k244a rapidly acquired compensatory mutations, t100k or e98a, and q145r-t237n respectively, which resto ...201727875780
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
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
a comprehensive procedure for antiviral inhibitor discovery using ev71 as an example.the prevalence of chronic viral infectious diseases, the emergence and re-emergence of new viral infections, and in particular, resistance to currently used antiviral drugs have led to increased demand for new antiviral strategies and reagents. increased understanding of the molecular mechanisms of viral infection has provided great potential for the discovery of new antiviral agents that target viral proteins or host factors. in this work, we introduce a comprehensive system using enteroviruses ...201726942222
impact of il-8-251a/t gene polymorphism on severity of disease caused by enterovirus 71 infection.the study was performed in ev71-infected patients, with 97 mild cases and 80 severe cases. il-8251a/t genotypes were determined by the polymerase chain reaction restriction fragment length polymorphism technique. severe cases had a significantly higher frequency of the il8-251 at and tt genotypes than mild cases (52.5 % vs. 49.5 % and 42.5 % vs. 30.9 %, respectively; p = 0.024). the frequency of il-8-251t alleles among the severe cases was also significantly higher than that of mild cases (68.7  ...201626497182
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
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
biological characteristics of different epidemic enterovirus 71 strains and their pathogeneses in neonatal mice and rhesus monkeys.hand, foot and mouth disease (hfmd) has been prevalent in china since 2008. enterovirus 71 (ev71) is a common causative agent of hfmd, and various strains of ev71 are prevalent worldwide. the ev71c4 subgenotype is the most endemic strain in china. however, few studies investigating the biological characteristics and pathogeneses of different c4 strains have been reported. therefore, the current study investigated 19 clinical ev71 strains in neonatal icr mice and neonatal rhesus monkeys by compar ...201626555165
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
association between angiopoietin-2 and enterovirus 71 induced pulmonary edema.to characterize pulmonary edema (pe) fluid induced by enterovirus 71 (ev71) infection, elucidate the relationship between angiopoietin-2 (ang-2) and pe, and explore the pathogenesis of pe.201626590154
interferon-mediated antiviral activities of angelica tenuissima nakai and its active components.angelica tenuissima nakai is a widely used commodity in traditional medicine. nevertheless, no study has been conducted on the antiviral and immune-modulatory properties of an aqueous extract of angelica tenuissima nakai. in the present study, we evaluated the antiviral activities and the mechanism of action of an aqueous extract of angelica tenuissima nakai both in vitro and in vivo. in vitro, an effective dose of angelica tenuissima nakai markedly inhibited the replication of influenza a virus ...201626727903
a dynamic model for the outbreaks of hand, foot, and mouth disease in taiwan.the first large outbreak of hand, foot, and mouth disease (hfmd) with severe complications primarily caused by enterovirus 71 was reported in taiwan in 1998. surveillance of hfmd to evaluate the spread of hfmd with and without infection control policy is needed. we developed a new dynamic epidemic susceptible-infected-recovered (sir) model to fit the surveillance data on containing valuable information on the severity of hfmd in order to accurately estimate the basic reproductive number (r 0) of ...201626567705
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
modification of the length and structure of the linker of n(6)-benzyladenosine modulates its selective antiviral activity against enterovirus 71.very recently, we demonstrated that n(6)-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. the present study is devoted to the structure optimization of another natural compound: n(6)-benzyladenosine. we mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the d-ribose residue. more than 30 analogues of n(6)-benzyladenosi ...201626854380
oblongifolin m, an active compound isolated from a chinese medical herb garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of erp57.there is no effective drug to treat ev71 infection yet. traditional chinese herbs are great resources for novel antiviral compounds. here we showed that oblongifolin m (om), an active compound isolated from garcinia oblongifolia, potently inhibited ev71 infection in a dose dependent manner. to identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. further studies showed that knockdown of ...201626848777
high-throughput characterization of virus-like particles by interlaced size-exclusion chromatography.the development and manufacturing of safe and effective vaccines relies essentially on the availability of robust and precise analytical techniques. virus-like particles (vlps) have emerged as an important and valuable class of vaccines for the containment of infectious diseases. vlps are produced by recombinant protein expression followed by purification procedures to minimize the levels of process- and product-related impurities. the control of these impurities is necessary during process deve ...201626845741
enterovirus 71 transmission by exosomes establishes a productive infection in human neuroblastoma cells.exosomes are small secreted cellular vesicles for intercellular communications which contain proteins, mrnas, and micrornas (mirnas). recent studies have shown that exosomes play an important role in the transmission of infectious agents including hepatitis c virus, human immunodeficiency virus, and so on. however, the role of exosomes in the transfer of enterovirus 71 (ev71) between host cells remains unknown. in this study, we show that the exosomes derived from ev71-infected rhabdomyosarcoma ...201626837894
comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase iii clinical trial.human enterovirus 71 (ev71) is a causative agent of hand, foot, and mouth disease (hfmd). in a previous phase iii trial in children, a human diploid cell-based inactivated ev71 vaccine elicited ev71 specific immune responses and protection against ev71 associated hfmd. this study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. this was a randomized, double-blinded, placebo-controlled, phase iii clinical trial of a human diploid vaccine carr ...201626837471
chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity.enterovirus 71 (ev71) is one of the causative agents of hand, foot, and mouth disease (hfmd), which sometimes leads to severe neurological disease and death in the asia-pacific region. in chinese medicine, hfmd is caused mainly by an accumulation of damp-heat and toxicity in the body. no effective drugs are currently available for the treatment and prevention of ev71 infection. this review summarizes the potential chinese herbal extracts and isolated compounds with antiviral activity against ev7 ...201626834824
the autophagic machinery in enterovirus infection.the enterovirus genus of the picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus a71, and enterovirus d68. they cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. currently, no effective vaccine is available against enteroviruses except for poliovirus. enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. some enteroviruses spread between cells via ...201626828514
a consistent orally-infected hamster model for enterovirus a71 encephalomyelitis demonstrates squamous lesions in the paws, skin and oral cavity reminiscent of hand-foot-and-mouth disease.enterovirus a71 (ev-a71) causes self-limiting, hand-foot-and-mouth disease (hfmd) that may rarely be complicated by encephalomyelitis. person-to-person transmission is usually by fecal-oral or oral-oral routes. to study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of hfmd and ev-a71 encephalomyelitis. tissues from orally-infected, 2-week-ol ...201626815859
ev71 virus-like particles produced by co-expression of capsid proteins in yeast cells elicit humoral protective response against ev71 lethal challenge.enterovirus 71 (ev71) is the most common causative pathogens of hand, foot and mouth disease (hfmd) associated with severe neurological complications. there is a great need to develop prophylactic vaccine against ev71 infection.201626809443
clinical characteristics and functional motor outcomes of enterovirus 71 neurological disease in children.enterovirus 71 (ev71) causes a spectrum of neurological complications with significant morbidity and mortality. further understanding of the characteristics of ev71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines.201626785318
innate immunity evasion by enteroviruses: insights into virus-host interaction.enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (ev) a71, ev-d68 and rhinovirus. infection with evs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. evs, which are positive-sense single-stranded rna viruses, trigger activation of the host antiviral innate immune responses through pathogen re ...201626784219
genome analysis of enterovirus 71 strains differing in mouse pathogenicity.enterovirus 71 (ev71) is a major causative agent of hand, foot, and mouth disease (hfmd) and is occasionally associated with severe neurological diseases. the investigation of virulence determinants of ev71 is rudimentary. therefore, it is important to understand the relationship between ev71 virulence and genomic information. in this study, a series of analyses about full-length genomic sequence were performed on six ev71 strains isolated from hfmd patients with either severe or mild clinical s ...201626781949
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