| annexin ii binds to capsid protein vp1 of enterovirus 71 and enhances viral infectivity. | enterovirus type 71 (ev71) causes hand, foot, and mouth disease (hfmd), which is mostly self-limited but may be complicated with a severe to fatal neurological syndrome in some children. understanding the molecular basis of virus-host interactions might help clarify the largely unknown neuropathogenic mechanisms of ev71. in this study, we showed that human annexin ii (anx2) protein could bind to the ev71 virion via the capsid protein vp1. either pretreatment of ev71 with soluble recombinant anx2 ... | 2011 | 21900167 |
| Selection and characterization of vaccine strain for Enterovirus 71 vaccine development. | Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in Asia because effective medications and prophylactic vaccine against EV71 infection are not available. Based on the success of inactivated poliovirus vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could be developed. Identification of EV71 vaccine strain which can grow to high titer in Vero cell and induce cross-genotype virus neutralizing antibody responses represents the first step in vac ... | 2011 | 22142585 |
| establishing china's national standards of antigen content and neutralizing antibody responses for evaluation of enterovirus 71 (ev71) vaccines. | enterovirus 71 (ev71) is a highly infectious agent that causes hand-foot-mouth disease (hfmd) in humans. effective vaccination against ev71 infection is critically important, given the recent outbreak of hfmd in the asia-pacific region, where it has shown significant mortality and morbidity. there is currently no approved anti-viral therapy available to treat the disease. while several vaccine manufacturers are actively developing ev71 vaccines, there are no international reference standards ava ... | 2011 | 22015395 |
| seroprevalence of enterovirus 71 and no evidence of crossprotection of enterovirus 71 antibody against the other enteroviruses in kindergarten children in taipei city. | background/purpose: enterovirus 71 (ev71) infection may cause severe neurological and cardiopulmonary complications, especially in preschool children. this study is to investigate the seroprevalence and seroconversion of ev71, and the crossprotection of ev71 antibody against other enteroviruses among kindergarteners. methods: overall 228 children in a public kindergarten were enrolled during two academic years, 2006 and 2007, in taipei, taiwan and we measured their ev71 neutralizing antibody. wh ... | 2011 | 22154997 |
| [advances in functional studies of nonstructural proteins and development of antiviral agents for enterovirus 71]. | human enterovirus 71 (ev71) is one of the major etiological agents for the hand, foot, and month disease (hfmd) and is causing frequent, widespread occurrence in the mainland of china. the single positive-stranded rna genome of ev71 is translated into a single polyprotein which is autocleavaged into structural and nonstructural proteins. the functions of many nonstructural proteins characterized in the life cycle of virus are potential targets for blocking viral replication. this article reviews ... | 2011 | 22010343 |
| epidemic characteristics of hand, foot, and mouth disease in shanghai from 2009 to 2010: enterovirus 71 subgenotype c4 as the primary causative agent and a high incidence of mixed infections with coxsackievirus a16. | background: enterovirus 71 (ev71) has been the main causative agent of hand, foot, and mouth disease (hfmd) outbreaks in recent years. a significant increase in the number of hfmd cases in china over the last 3 y has made the public prevention and therapy of this disease a critical issue. methods: a total of 3208 hfmd patients in shanghai during the period 2009 to 2010 were analyzed; 437 clinical specimens were collected for the determination of causative pathogens. eight of the isolated ev71 st ... | 2011 | 22176514 |
| characterization of an outbreak of hand, foot, and mouth disease in nanchang, china in 2010. | recent outbreaks of human enterovirus 71 (ev71) infection and ev71-associated hand, foot, and mouth disease (hfmd) in china have affected millions and potentially lead to life-threatening complications in newborns. furthermore, these outbreaks represent a significant global public health issue in the world. understanding the epidemiology of hfmd and ev71 infection and their transmission patterns in china is essential for controlling outbreaks. however, no studies on the outbreaks of hfmd and ev7 ... | 2011 | 21980416 |
| Rhombencephalitis / brainstem encephalitis. | Rhombencephalitis (RE) is a syndrome of multiple causes and multiple outcomes. Most authors now use the terms "rhombencephalitis" and "brainstem encephalitis" interchangeably even though anatomically they are slightly different. The etiologic categories of RE include infections, autoimmune diseases, and paraneoplastic syndromes (PNS). Listeria is the most common cause of infectious RE. Listeria RE primary occurs in healthy young adults. It usually occurs as a biphasic time course with a flu-like ... | 2011 | 21956758 |
| [Construction and identification of attenuated Salmonella which harboring enterovirus 71 VP1 gene]. | To develop attenuated Salmonella which harboring enterovirus 71 (EV71) VP1 gene. | 2011 | 21863634 |
| [Complete genomic sequence analysis on human enterovirus 71 strain in Guangzhou, in 2008 and 2010]. | To study the genomic genotypes and variation of human enterovirus 71 (EV71) infected infants in Guangzhou city, in 2008 and 2010. | 2011 | 21933544 |
| molecular characterization and complete genome analysis of human enterovirus 71 and coxsackievirus a16 from children with hand, foot and mouth disease in thailand during 2008-2011. | hand, foot and mouth disease (hfmd) has mostly been caused by enterovirus 71 (ev71) and coxsackievirus a16 (ca16). ca 16 was the most common cause of hfmd in 2010. ev71 had a high prevalence in 2008-2009 and has been identified with a higher frequency since 2011. nearly complete genome sequences of three ev71 strains (2008-2009 strains) and two ca16 strains (2010 strains) obtained from outbreaks in thailand in 2008 to 2010 were characterized. based on a phylogenetic tree of the complete vp1 regi ... | 2011 | 21898187 |
| MEK1-ERKs signal cascade is required for the replication of Enterovirus 71 (EV71). | The role of the MEK1-ERK signaling cascade in the replication cycle of Enterovirus 71 (EV71), the primary cause of hand, foot and mouth disease (HFMD), has been analyzed. In vitro infection with EV71 induced a biphasic activation of ERK. The two phases of activation appeared to be triggered by different mechanisms, with the first phase being activated by the binding of viral particles to the membrane receptor of host cells and the second probably being in response to the production of new virus ... | 2012 | 22101247 |
| [comparisons of epidemiological and clinical characteristics in children with hand-foot-mouth disease caused by enterovirus 71 and coxackievirus a16]. | to compare the differences of epidemiological and clinical characteristics in children with hand-foot-mouth disease (hfmd) caused by coxsackievirus a16 (ca16) and enterovirus 71 (ev71). | 2011 | 21849112 |
| characterization of a monoclonal antibody against the 3d polymerase of enterovirus 71 and its use for the detection of human enterovirus a infection. | over the last decade, frequent epidemic outbreaks of hand, foot and mouth disease have been observed in the asia-pacific region. hand, foot and mouth disease is caused by different viruses from the enterovirus family, mainly coxsackievirus a16 and enterovirus 71 (ev71) from the human enterovirus a family. severe disease and neurological complications are associated more often with ev71 infection, and can lead occasionally to fatal brain stem encephalitis in young children. the rapid progression ... | 2011 | 22226793 |
| evaluation of human enterovirus 71 and coxsackievirus a16 specific immunoglobulin m antibodies for diagnosis of hand-foot-and-mouth disease. | abstract: background: hand-foot-and-mouth disease (hfmd) is caused mainly by the human enterovirus type 71 (hev71) and the coxsackievirus a group type 16 (cva16). large outbreaks of disease have occurred frequently in the asia-pacific region. reliable methods are needed for diagnosis of hfmd in childen. igm-capture elisa, with its notable advantages of convenience and low cost, provides a potentially frontline assay. we aimed to evaluate the newly developed igm-capture elisas for hev71 and cva1 ... | 2012 | 22234169 |
| enterovirus 71 disrupts interferon signaling by reducing the interferon receptor i. | the recent outbreak of enterovirus 71 (ev71) infected millions of children and caused over 1,000 deaths. to date, neither effective vaccine nor antiviral treatment is available for ev71 infection. interferons (ifns) have been successfully applied for treating patients such as hepatitis b and c viral infections for decades but failed to treat ev71 infections. here, we provide the evidence that ev71 antagonizes type i ifn signaling by reducing the level of interferon receptor 1 (ifnar1). we show t ... | 2012 | 22258259 |
| in vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection. | enterovirus 71(ev71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. more effective antiviral drugs are needed to prevent or reduce ev71-related disease and complications. however, there are no standard models currently in use to evaluate activity against ev71 infection both in vitro and in vivo. in this study, the activity of ribavirin and pleconaril against ev71 infection was evaluated in two models. an in vitro e ... | 2012 | 22245989 |
| detection of human enterovirus 71 and coxsackievirus a16 in children with hand, foot and mouth disease in china. | the aims of the present study were to investigate the genetic characteristics of enterovirus 71 (ev71) and coxsackievirus a16 (cva16) strains in china and to evaluate the relationship between the genotypes of cva16 and ev71 and their geographical distribution. a total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (hfmd) in zhejiang province. the presence of enteroviruses was determined ... | 2012 | 22218731 |
| distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications. | abstract: background: to explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (hfmd) complicated with nervous system disease. 234 hospitalized hfmd patients treated in shengjing hospital, liaoning province were analyzed retrospectively. based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. based on the detected p ... | 2012 | 22230340 |
| detection of human enterovirus 71 reverse transcription loop-mediated isothermal amplification (rt-lamp). | aims: in this study, a one-step, single-tube reverse transcription loop-mediated isothermal amplification (rt-lamp) assay was developed and validated for the detection of human enterovirus 71 (ev71), the major aetiological agent of hand, foot and mouth disease (hfmd). methods and results: reverse transcription loop-mediated isothermal amplification assay was optimized to amplify vp1 gene in the presence of a specific primer set and bst dna polymerase at an isothermal temperature of 63°c for 1 ... | 2012 | 22256968 |
| [studies on anti-ev71 virus activity of traditional chinese medicine and its clinical application in treatment of hfmd]. | hand-foot-and-mouth disease is caused by intestinal virus infection. the viruses coxsackie a16 (ca16) and enterovirus 71 (ev71) are the main pathogens. between them, the virus ev71 is more dangerous and easier to cause serious complications, which leads to death or disability. currently, there are no effective antiviral drugs to treat ev71 infection. therefore, developing an effective drug against ev71 virus activity is significant. it has a huge potency of screening the anti-ev71 components and ... | 2011 | 22393752 |
| a flavobacterium lindanitolerans strain isolated from the ascites sample of a chinese patient with ev71 virus infection. | a strain of flavobacterium lindanitolerans isolated from a sick child's ascites was described. the 16s rrna gene of the strain was 100% identical to that of flavobacterium lindanitolerans which was first identified in india in 2008. it was first described that the isolate required x factor (hemin) for growth in the optimal conditions of 37 °c with 5% co(2). the isolate produced indole and h(2)s. it did not present hemolytic feature on blood agar. | 2011 | 22365408 |
| [virologic and epidemiological characteristics of non-polio infection in croatia over a ten-year period (2000-2009)]. | the aim of the present study was to show the virologic and epidemiological characteristics of non-polio enterovirus (npev) infection over a ten-year period in croatia. | 2011 | 22359891 |
| [a pathogen analysis within 174 cases of hand-foot-mouth disease in the summer of 2009]. | to analyze the pathogen and characteristics of the serum types of enterovirus of hand-foot-and-mouth disease (hfmd) in the summer, 2009. | 2011 | 22338230 |
| [analysis on detection of enterovirus nucleotides in feces samples of hand-foot-mouth disease patients after recovery]. | to explore the duration of enterovirus (ev) nucleotides positive in feces samples of hand-foot-mouth disease (hfmd) patients after recovery. | 2011 | 22336339 |
| [acute kidney injury in critically ill children infected with influenza a virus (h1n1) and enterovirus 71]. | to analyze the clinical characteristics of acute kidney injury (aki) in critically ill childhood patients with influenza a virus (h1n1) and enterovirus 71 (ev71), and to study the significance of the serum creatinine and urine output in diagnosis of aki. | 2011 | 22336307 |
| [recent advances in reverse genetics of enterovirus 71]. | | 2011 | 22263276 |
| detection and characterization of enterovirus associated with herpangina and hand, foot, and mouth disease in seoul, korea. | human enteroviruses (hevs) are a major cause of herpangina, hfmd (hand, foot, and mouth disease), and other neurological diseases in seoul, korea. | 2011 | 22239028 |
| enterovirus type 71 neutralizing antibodies in the serum of macaque monkeys immunized with ev71 virus-like particles. | enterovirus type 71 (ev71) is a virulent form of enteroviruses causing hospitalizations for children less than three years of age. currently there are no anti-viral therapies or vaccines available for ev71. due to the high risk of poliomyelitis-like paralysis and fatal encephalitis, an effective vaccine to ev71 could potentially prevent virus-induced morbidity and mortality. in this study, we first tested a potential ev71 vaccine candidate based on virus-like particles (vlp). we vaccinated macaq ... | 2011 | 22214888 |
| [association of hla-g 14bp gene polymorphisms and plasma shla-g level with susceptibility to ev71 infection in children]. | explore the relationship between the hla-g 14bp insertion/deletion polymorphism and the infection of enterovirus 71 (ev71) for children. | 2012 | 23627021 |
| [transmission and prevalence patterns of c4a evolutionary lineage of human enterovirus 71 circulating in mainland of china, 2008-2010]. | to understand the evolutionary relationship between the c4a evolutionary lineage of human enterovirus 71 (hev71) strains circulating in mainland of china during 2008-2010 and 2008 fuyang strains and study the prevalence and transmission patterns of 2008 fuyang strains. | 2012 | 23627020 |
| [detection the pathogens and analysis the clinical characteristics in children with hand, foot and mouth disease in shanghai during 2009-2011]. | to investigate the epidemic characteristics of etiological agents and analyze the clinic differences in children with hand, foot and mouth diseases in shanghai. | 2012 | 23547454 |
| [isolation and sequence analysis on virus of hfmd with encephalitis in yantal city]. | to learn about the pathogen spectrum and genetic characterization of hfmd with encephalitis in yantai city. | 2012 | 23547453 |
| enterovirus 71 causes hand, foot and mouth disease outbreak in cambodia. | | 2012 | 23448647 |
| [genetic characteristics of enterovirus 71 vp1 and epidemiology of hand-foot-mouth disease in xinxiang in 2011]. | the study was performed to examine the enterovirus 71(ev71) vp1 genetic feature and the epidemiology of hand-foot-mouth disease (hfmd) in xinxiang in 2011. real-time rt-pcr was used for the detection of pan-enterovirus, coxsackievirus a 16(ca16) and ev71 from stool specimens of hfmd. the vp1 region was amplified from 10 ev71 positive samples and the products were sequenced. ev71 genotypes were characterized by homology and phylogenetic tree analyses. additionally, epidemic data of xinxiang hfmd ... | 2012 | 23367569 |
| [comparison of different molecular assays for the rapid detection of enterovirus 71 (ev71)]. | molecular detection of enterovirus (ev)71 rna based on pcr methods is a quick and sensitive approach. at present, different pcr-based methods for ev71 rna detection are available, but comparisons of results obtained using different approaches are limited. this study is to compare the analytical sensitivity and specificity of different real-time reverse transcription-polymerase chain reaction (rrt-pcr) and conventional reverse transcription-polymerase chain reaction (crt-pcr) assays for enterovir ... | 2012 | 23367568 |
| [analysis on epidemiology and the main clinical symptoms of viral encephalitis in gansu, 2009-2011]. | to understand the epidemiological characteristics and the main clinical symptoms of viral encephalitis in gansu. | 2012 | 23363967 |
| [etiology surveillance of hand-foot-mouth disease in henan province between 2008 and 2011]. | to understand etiological types and distribution features of hand-foot-mouth disease (hfmd) in henan province between 2008 and 2011. | 2012 | 23363860 |
| [typing and identification of non-polio enterovirus from acute flaccid paralysis cases in ningxia, 1997-2011]. | to identify the serotype of 73 non-polio enterovirus (npev) strains from acute flaccid paralysis (afp) cases in ningxia province, during 1997 - 2011. | 2012 | 23290905 |
| [etiological detection of severe hand-food-mouth disease and related genetic characteristics of enterovirus type 71 infection in beijing, 2010]. | to study the etiological detection on samples from severe hand-foot-mouth disease (hfmd) cases and the genetic characteristics of enterovirus type 71 (ev71) isolates from severe patients in beijing, 2010. | 2012 | 23290804 |
| enterovirus 71-induced neurological disorders in young gerbils, meriones unguiculatus: development and application of a neurological disease model. | a reliable disease model mimicking enterovirus 71 (ev71) infection in humans is essential for understanding pathogenesis and for developing a safe and effective vaccine. commonly used rodent models including mouse or rat models are not suitable for vaccine evaluation because the rodents are resistant to ev71 infection after they reach the age of 6 days. in this study, 21-day-old gerbils inoculated intraperitoneally (ip) with a non mouse-adapted ev71 strain developed neurological lesion-related s ... | 2012 | 23284845 |
| evaluation of a direct reverse transcription loop-mediated isothermal amplification method without rna extraction for the detection of human enterovirus 71 subgenotype c4 in nasopharyngeal swab specimens. | human enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease (hfmd) worldwide and has been associated with neurological complications which resulted in fatalities during recent outbreak in asia pacific region. a direct reverse transcription loop-mediated isothermal amplification (direct rt-lamp) assay using heat-treated samples without rna extraction was developed and evaluated for the detection of ev71 subgenotype c4 in nasopharyngeal swab specimens. the analytical ... | 2012 | 23272248 |
| [cloning, expression and antigenic analysis of vp1-vp4 gene encoding the structural protein of coxsackie virus a16]. | to clone and express vp1-vp4 genes encoding the structural proteins of coxsackie virus a16 and analyze the antigenicity of the expressed recombinant proteins. | 2012 | 23268395 |
| development and characterization of a stable egfp enterovirus 71 for antiviral screening. | enterovirus 71 (ev71) is one of the major causative agents for hand, foot, and mouth disease. there is currently no clinically approved vaccine or antiviral treatment for ev71 infection. to facilitate antiviral drug discovery, we developed an infectious cdna clone of an epidemic strain of ev71 and a stable egfp reporter ev71. the reporter virus was generated by engineering the egfp gene between the 5' untranslated region and vp4 gene of the ev71 genome. vero cells transfected with the cdna clone ... | 2012 | 23267829 |
| grp78/dna k is a target for nexavar/stivarga/votrient in the treatment of human malignancies, viral infections and bacterial diseases. | prior tumor cell studies have shown that the drugs sorafenib (nexavar) and regorafenib (stivarga) reduce expression of the chaperone grp78. sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (votrient) interacted with sildenafil (viagra) to further rapidly reduce grp78 levels in eukaryotes and as single agents to reduce dna k levels in prokaryotes. similar data were obtained in tumor cells in vitro and in drug-treated mice for: hsp70, mitochondrial hsp70, hsp60, hsp56, hsp40, hsp10, ... | 2015 | 25858032 |
| ev71 vaccine, an invaluable gift for children. | enterovirus 71 (ev71) is a major pathogen for severe hand, foot and mouth disease (hfmd). development of vaccines against ev71 would be the most effective approach to prevent the ev71 outbreak. research and development (r&d) of ev71 vaccine was carried out in several asian countries. currently three companies in mainland china have completed phase iii clinical trials of inactivated ev71 whole-virus vaccines, whereas the other two companies have completed phase i clinical trials separately in tai ... | 2014 | 25505956 |
| a broadly cross-protective vaccine presenting the neighboring epitopes within the vp1 gh loop and vp2 ef loop of enterovirus 71. | human enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are the major etiological agents of hand, foot and mouth disease (hfmd) and are often associated with neurological complications. currently, several vaccine types are being developed for ev71 and ca16. in this study, we constructed a bivalent chimeric virus-like particle (vlp) presenting the vp1 (aa208-222) and vp2 (aa141-155) epitopes of ev71 using hepatitis b virus core protein (hbc) as a carrier, designated hbc-e1/2. immunization with ... | 2015 | 26243660 |
| enterovirus-71 virus-like particles induce the activation and maturation of human monocyte-derived dendritic cells through tlr4 signaling. | enterovirus 71 (ev71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. we recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with ev71 virus-like particles (vlps), with a morphology resembling that of infectious ev71 virions but not containing a viral genome, which could potentially be safe as a vaccine for ev71. to elucidate the mechanisms through which ev71 vlps induce cell-med ... | 2014 | 25360749 |
| japanese encephalitis virus replicon-based vaccine expressing enterovirus-71 epitope confers dual protection from lethal challenges. | to construct safer recombinant flavivirus vaccine, we exploited japanese encephalitis virus (jev) replicon-based platform to generate single-round infectious particles (srips) that expressed heterologous neutralizing epitope sp70 derived from enterovirus-71 (ev71). such pseudo-infectious virus particles, named srip-sp70, although are not genuine viable viruses, closely mimic live virus infection to elicit immune responses within one round of viral life cycle. | 2015 | 26362772 |
| adaptation of enterovirus 71 to adult interferon deficient mice. | non-polio enteroviruses, including enterovirus 71 (ev71), have caused severe and fatal cases of hand, foot and mouth disease (hfmd) in the asia-pacific region. the development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. in this study, a mouse adapted ev71 strain was produced by conducting serial passages through a129 (α/β interferon (ifn) receptor deficient) and ag129 (α/β, γ ifn receptor deficient) mice. a b2 sub genotype of ... | 2013 | 23527208 |
| enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor. | enterovirus 71 (ev-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. to date, four ev-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish ev-71 infection, implying that there is an as yet undiscovered receptor(s). since ev-71 has a wide range of tissue tropisms, we hypothesize that ev-71 infections ma ... | 2012 | 23097443 |
| amphotericin b inhibits enterovirus 71 replication by impeding viral entry. | enterovirus 71 (ev71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. there is thus an urgent need to find new treatments to control ev71 infection. in this study, we report potent inhibition of ev71 by a polyene antibiotic amphotericin b. amphotericin b profoundly diminished the expression of ev71 rna and viral proteins in the rd cells and the hek293 cells. as a result, ev71 production was inhibited by amphotericin b with an ... | 2016 | 27608771 |
| identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of coxsackievirus a16. | coxsackievirus a16 (ca16) and enterovirus 71 (ev71) are two main causative pathogens of hand, foot and mouth disease (hfmd). unlike ev71, virulence determinants of ca16, particularly within 5' untranslated region (5'utr), have not been investigated until now. here, a series of nucleotides present in 5'utr of lethal but not in non-lethal ca16 strains were screened by aligning nucleotide sequences of lethal circulating changchun ca16 and the prototype g10 as well as non-lethal shzh05 strains. a re ... | 2016 | 26861413 |
| hur and ago2 bind the internal ribosome entry site of enterovirus 71 and promote virus translation and replication. | ev71 (enterovirus 71) rna contains an internal ribosomal entry site (ires) that directs cap-independent initiation of translation. ires-dependent translation requires the host's translation initiation factors and ires-associated trans-acting factors (itafs). we reported recently that mrna decay factor auf1 is a negative-acting itaf that binds ires stem-loop ii. we also reported that the small rna-processing enzyme dicer produces at least four small rnas (vsrnas) from the ev71 ires. one of these, ... | 2015 | 26451954 |
| discovery of itraconazole with broad-spectrum in vitro antienterovirus activity that targets nonstructural protein 3a. | there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections, which remain a substantial threat to public health. to discover inhibitors that can be immediately repurposed for treatment of enterovirus infections, we developed a high-throughput screening assay that measures the cytopathic effect induced by enterovirus 71 (ev71) to screen an fda-approved drug library. itraconazole (itz), a triazole antifungal agent, was identified as an effective inhi ... | 2015 | 25691649 |
| the role of misshapen nck-related kinase (mink), a novel ste20 family kinase, in the ires-mediated protein translation of human enterovirus 71. | human enterovirus 71 (ev71) commonly causes hand, foot and mouth disease in young children, and occasional occurrences of neurological complications can be fatal. in this study, a high-throughput cell-based screening on the serine/threonine kinase sirna library was performed to identify potential antiviral agents against ev71 replication. among the hits, misshapen/niks-related kinase (mink) was selected for detailed analysis due to its strong inhibitory profile and novelty. in the investigation ... | 2015 | 25747578 |
| enterovirus 71 induces mitochondrial reactive oxygen species generation that is required for efficient replication. | redox homeostasis is an important host factor determining the outcome of infectious disease. enterovirus 71 (ev71) infection has become an important endemic disease in southeast asia and china. we have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. the detailed mechanism for reactive oxygen species (ros) generation in infected cells remains elusive. in the current study, we demonstrate that mitochondria were a major ro ... | 2014 | 25401329 |
| a cytoplasmic rna virus generates functional viral small rnas and regulates viral ires activity in mammalian cells. | the roles of virus-derived small rnas (vsrnas) have been studied in plants and insects. however, the generation and function of small rnas from cytoplasmic rna viruses in mammalian cells remain unexplored. this study describes four vsrnas that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. viral infection produced substantial levels (>10(5) copy numbers per cell) of vsrna1, one of the four vsrnas. we also demonstrated that dicer is involved in ... | 2014 | 25352551 |
| initial evidence on differences among enterovirus 71, coxsackievirus a16 and coxsackievirus b4 in binding to cell surface heparan sulphate. | cell surface heparan sulphate (hs) mediates infection for many viruses from diverse families. we demonstrated significant antiviral potencies for a number of hs mimetics against a cloned strain of enterovirus 71 (ev71) in a previous study. thus, the involvement of hs in mediating viral infection of isolates of human enteroviruses was investigated in vero and human neural cells in the present work. in both cell lines, heparin and pentosan polysulphate significantly inhibited both infection and at ... | 2013 | 25674594 |
| in vivo time-related evaluation of a therapeutic neutralization monoclonal antibody against lethal enterovirus 71 infection in a mouse model. | enterovirus 71 (ev71) is a neurotropic virus capable of inducing severe neurological symptoms and death. no direct targeting antivirals are useful in the treatment of severe ev71 infection. because of low toxicity and good specificity, monoclonal antibodies (mab) are a potential candidate for the treatment of viral infections. therefore, we developed an ev71-specific conformational mab with high in vitro cross-neutralization activity to heterologous ev71 subgenotypes. the in vivo treatment exper ... | 2014 | 25279734 |
| inhibition of enveloped viruses infectivity by curcumin. | curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (ha) activity. this study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. in all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. in contrast, the nonenveloped enterovirus 71 r ... | 2013 | 23658730 |
| er stress, autophagy, and rna viruses. | endoplasmic reticulum (er) stress is a general term for representing the pathway by which various stimuli affect er functions. er stress induces the evolutionarily conserved signaling pathways, called the unfolded protein response (upr), which compromises the stimulus and then determines whether the cell survives or dies. in recent years, ongoing research has suggested that these pathways may be linked to the autophagic response, which plays a key role in the cell's response to various stressors ... | 2014 | 25140166 |
| curcumin inhibits the replication of enterovirus 71 in vitro. | human enterovirus 71 (ev71) is the main causative pathogen of hand, foot, and mouth disease (hfmd) in children. the epidemic of hfmd has been a public health problem in asia-pacific region for decades, and no vaccine and effective antiviral medicine are available. curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. in this study, we demonstrated that curcumin showed potent antiviral effect again ev71. in vero cells infected ... | 2014 | 26579397 |
| enterovirus 71 induces dsrna/pkr-dependent cytoplasmic redistribution of grp78/bip to promote viral replication. | grp78/bip is an endoplasmic reticulum (er) chaperone protein with the important function of maintaining er homeostasis, and the overexpression of grp78/bip alleviates er stress. our previous studies showed that infection with enterovirus 71 (ev71), a (+)rna picornavirus, induced grp78/bip upregulation; however, ectopic grp78/bip overexpression in er downregulates virus replication and viral particle formation. the fact that a virus infection increases grp78/bip expression, which is unfavorable f ... | 2016 | 27004760 |
| neglected tropical diseases among the association of southeast asian nations (asean): overview and update. | the ten member states of the association of southeast asian nations (asean) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (ntds). almost 200 million people live in extreme poverty in asean countries, mostly in the low or lower middle-income countries of indonesia, the philippines, myanmar, viet nam, and cambodia, and many of them are affected by at least one ntd. however, ntds are prevalent even among upper mi ... | 2015 | 25880767 |
| proteomic analysis of human brain microvascular endothelial cells reveals differential protein expression in response to enterovirus 71 infection. | 2d dige technology was employed on proteins prepared from human brain microvascular endothelial cells (hbmec), to study the differentially expressed proteins in cells at 0 h, 1 h, 16 h, and 24 h after infection. proteins found to be differentially expressed were identified with matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (malditof/tof ms) analysis. we identified 43 spots showing changes of at least 2.5 fold up- or downregulated expressions in ev71- ... | 2015 | 25821824 |
| far upstream element binding protein 1: a commander of transcription, translation and beyond. | the far upstream binding protein 1 (fbp1) was first identified as a dna-binding protein that regulates c-myc gene transcription through binding to the far upstream element (fuse) in the promoter region 1.5 kb upstream of the transcription start site. fbp1 collaborates with tfiih and additional transcription factors for optimal transcription of the c-myc gene. in recent years, mounting evidence suggests that fbp1 acts as an rna-binding protein and regulates mrna translation or stability of genes, ... | 2012 | 22926519 |
| rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions. | the development of vaccines against infectious diseases represents one of the most important contributions to medical science. however, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. the biomimetic nucleating p ... | 2013 | 23589862 |
| a laboratory evaluation of medicinal herbs used in china for the treatment of hand, foot, and mouth disease. | enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the causative agents of hand, foot, and mouth disease (hfmd). during recent epidemics of hfmd in china, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. there have been no microbiological studies to validate their usefulness for hfmd. we selected 12 commonly used herbs for hfmd from government recommended guidelines as well as published reports and tested fo ... | 2013 | 23554831 |
| protective efficacy of vp1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human scarb2-transgenic mice. | hand-foot-mouth diseases (hfmd) caused by enterovirus 71 (ev71) and coxsackievirus 16 (cva16) in children have now become a severe public health issue in the asian-pacific region. recently we have successfully developed transgenic mice expressing human scavenger receptor class b member 2 (hscarb2, a receptor of ev71 and cva16) as an animal model for evaluating the pathogenesis of enterovirus infections. in this study, hscarb2-transgenic mice were used to investigate the efficacy conferred by a p ... | 2013 | 23936115 |
| formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of h5n1/ev71/jev. | combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (h5n1/h1n1), enterovirus 71 (ev71), and/or japanese encephalitis virus (jev) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. we demonstrated that the antigeni ... | 2013 | 23838466 |
| children of rural-to-urban migrant workers in china are at a higher risk of contracting severe hand, foot and mouth disease and ev71 infection: a hospital-based study. | the incidence and severity of hand, foot and mouth disease have increased in mainland china since 2008. therapies and vaccines are currently at different stages of development. this study aimed to determine the social factors associated with the outbreaks and severity of the disease in chinese children. a multicentre, prospective, case-controlled study was conducted in shanghai, chongqing, guangzhou and shantou to identify the sociodemographic and behavioural risk factors for hand, foot and mout ... | 2013 | 26038441 |
| heat shock protein 90: role in enterovirus 71 entry and assembly and potential target for therapy. | although several factors participating in enterovirus 71 (ev71) entry and replication had been reported, the precise mechanisms associated with these events are far from clear. in the present study, we showed that heat shock protein 90 (hsp90) is a key element associated with ev71 entry and replication in a human rhabdomyosarcoma of rd cells. inhibition of hsp90 by pretreating host cells with hsp90β sirna or blocking hsp90 with a hsp90-specific antibody or geldanamycin (ga), a specific inhibitor ... | 2013 | 24098578 |
| immunologic characterization of cytokine responses to enterovirus 71 and coxsackievirus a16 infection in children. | viral encephalitis is a serious complication of hand, foot, and mouth disease (hfmd), but characteristics of cytokines response in enterovirus 71 (ev-71) and/or coxsackievirus a16 (cv-a16) associated hfmd with or without viral encephalitis remained unclear.we performed a multigroup retrospective study and compared the serum cytokines concentrations among 16 encephalitis patients infected with ev-71 and cv-a16, 24 encephalitis patients with single ev-71 infection, 34 mild hfmd patients with ev-71 ... | 0 | 26166120 |
| disease burden of enterovirus 71 in rural central china: a community-based survey. | in recent years, the epidemics of hand, foot, and mouth disease (hfmd) centered in the asian-pacific region have been characterized by high morbidity and mortality. enterovirus 71 (ev71) infections were responsible for the majority of the infections leading to severe cases of hfmd and death. this is a community-based survey aimed to estimate the disease burden of ev71 in rural central china, especially for hfmd. from 2011 to 2013, demographic and socio-economic data were gathered from 343 ill ch ... | 0 | 26158689 |
| parallel mrna and microrna profiling of hev71-infected human neuroblastoma cells reveal the up-regulation of mir-1246 in association with dlg3 repression. | human enterovirus 71 (hev71) has emerged as the leading cause of viral encephalitis in children in most asian countries. the roles of host mirnas in the neurological pathogenesis of hev71 infection remain unknown. in the present study, comprehensive mirna expression profiling in hev71-infected human neuroblastoma sh-sy5y cells was performed using the affymetrix gene chip microarray assay and was validated using real-time rt-pcr. among the 69 differentially expressed mirnas, mir-1246 was specific ... | 2014 | 24739954 |
| inhibition of enterovirus 71 replication by 7-hydroxyflavone and diisopropyl-flavon7-yl phosphate. | enterovirus 71 (ev71) is the major causative agent of hand, foot, and mouth disease, which has been continuously prevalent in asia in recent years. in children, severe cases can lead to death, and no prophylactic or therapeutic measures against ev71 infection are available. the 3c proteases of ev71 play an important role in viral replication and are an ideal drug target. in previous work, we resolved the crystal structure for ev71 3cpro. in this report, we took advantage of the automated docking ... | 2014 | 24664133 |
| anti-enterovirus 71 effects of chrysin and its phosphate ester. | enterovirus 71 (ev71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. the anti-ev71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. by using the predicting program autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3cpro activity. replication of viral rna and production of viral capsid protein and the infect ... | 2014 | 24598537 |
| enterovirus 2apro targets mda5 and mavs in infected cells. | rig-i-like receptors (rlrs) mda5 and rig-i are key players in the innate antiviral response. upon recognition of viral rna, they interact with mavs, eventually inducing type i interferon production. the interferon induction pathway is commonly targeted by viruses. how enteroviruses suppress interferon production is incompletely understood. mda5 has been suggested to undergo caspase- and proteasome-mediated degradation during poliovirus infection. additionally, mavs is reported to be cleaved duri ... | 2014 | 24390337 |
| characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection. | enterovirus 71 (ev71) is the main causative agent of hand, foot and mouth disease (hfmd) and is associated with severe neurologic complications and mortalities. at present, there is no vaccine or therapeutic available for treatment. | 2012 | 22279543 |
| the c terminus of the core β-ladder domain in japanese encephalitis virus nonstructural protein 1 is flexible for accommodation of heterologous epitope fusion. | ns1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (er), where ns1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. here, by using a trans-complementation assay, we identified the c-terminal end of ns1 derived from japanese encephalitis virus (jev), which ... | 2015 | 26559836 |
| innate immunity and immune evasion by enterovirus 71. | enterovirus 71 (ev71) is a major infectious disease affecting millions of people worldwide and it is the main etiological agent for outbreaks of hand foot and mouth disease (hfmd). infection is often associated with severe gastroenterological, pulmonary, and neurological diseases that are most prevalent in children. currently, no effective vaccine or antiviral drugs exist against ev71 infection. a lack of knowledge on the molecular mechanisms of ev71 infection in the host and the virus-host inte ... | 2015 | 26694447 |
| additive promotion of viral internal ribosome entry site-mediated translation by far upstream element-binding protein 1 and an enterovirus 71-induced cleavage product. | the 5' untranslated region (5' utr) of the enterovirus 71 (ev71) rna genome contains an internal ribosome entry site (ires) that is indispensable for viral protein translation. due to the limited coding capacity of their rna genomes, ev71 and other picornaviruses typically recruit host factors, known as ires trans-acting factors (itafs), to mediate ires-dependent translation. here, we show that ev71 viral proteinase 2a is capable of cleaving far upstream element-binding protein 1 (fbp1), a posit ... | 2016 | 27780225 |
| enterovirus a71 dna-launched infectious clone as a robust reverse genetic tool. | enterovirus a71 (ev-a71) causes major outbreaks of hand, foot and mouth disease, and is occasionally associated with neurological complications and death in children. reverse genetics is widely used in the field of virology for functional study of viral genes. for ev-a71, such tools are limited to clones that are transcriptionally controlled by t7/sp6 bacteriophage promoter. this is often time-consuming and expensive. here, we describe the development of infectious plasmid dna-based ev-a71 clone ... | 2016 | 27617744 |
| immunodominant igm and igg epitopes recognized by antibodies induced in enterovirus a71-associated hand, foot and mouth disease patients. | enterovirus a71 (ev-a71) is one of the main causative agents of hand, foot and mouth disease (hfmd). unlike other enteroviruses that cause hfmd, ev-a71 is more frequently associated with severe neurological complications and fatality. to date, no effective licensed antivirals are available to combat ev-a71 infection. little is known about the immunogenicity of viral non-structural proteins in humans. previous studies have mainly focused on characterization of epitopes of ev-a71 structural protei ... | 2016 | 27806091 |
| molecular characterization of human enteroviruses in the central african republic: uncovering wide diversity and identification of a new human enterovirus a71 genogroup. | human enteroviruses (hev) are among the most common viruses infecting humans. their circulation has been widely studied in most parts of the world but not in sub-saharan africa, where poliomyelitis remains prevalent. we report here the molecular characterization of 98 nonpoliovirus (non-pv) hev strains isolated from 93 randomly selected cell culture-positive supernatants from stool samples collected from 1997 through 2006 from children with acute flaccid paralysis living in the central african r ... | 2012 | 22337981 |
| inhibition of enterovirus 71 (ev-71) infections by a novel antiviral peptide derived from ev-71 capsid protein vp1. | enterovirus 71 (ev-71) is the main causative agent of hand, foot and mouth disease (hfmd). in recent years, ev-71 infections were reported to cause high fatalities and severe neurological complications in asia. currently, no effective antiviral or vaccine is available to treat or prevent ev-71 infection. in this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of ev-71. ninety five synthetic peptides (15-mers) overlapping the entire e ... | 2012 | 22563456 |
| single neutralizing monoclonal antibodies targeting the vp1 gh loop of enterovirus 71 inhibit both virus attachment and internalization during viral entry. | antibodies play a critical role in immunity against enterovirus 71 (ev71). however, how ev71-specific antibodies neutralize infections remains poorly understood. here we report the working mechanism for a group of three monoclonal antibodies (mabs) that potently neutralize ev71. we found that these three mabs (termed d5, h7, and c4, respectively) recognize the same conserved neutralizing epitope within the vp1 gh loop of ev71. single mabs in this group, exemplified by d5, could inhibit ev71 infe ... | 2015 | 26401034 |
| protease 2a induces stress granule formation during coxsackievirus b3 and enterovirus 71 infections. | stress granules (sgs) are granular aggregates in the cytoplasm that are formed under a variety of stress situations including viral infection. previous studies indicate that poliovirus, a member of picornaviridae, can induce sg formation. however, the exact mechanism by which the picornaviruses induce sg formation is unknown. | 2014 | 25410318 |
| human igg subclasses against enterovirus type 71: neutralization versus antibody dependent enhancement of infection. | the emerging human enterovirus 71 (ev71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. human intravenous immunoglobulin (ivig) is clinical used in treating severe ev71 infections. however, the discovery of antibody dependent enhancement (ade) of ev71 infection illustrates the complex roles of antibody in controlling ev71 infection. in this study, to identify the distinct role of each igg subclass on neutralization and enhancement of ev ... | 2013 | 23700449 |
| human microrna hsa-mir-296-5p suppresses enterovirus 71 replication by targeting the viral genome. | enterovirus 71 (ev71) has emerged as a major cause of neurological disease following the near eradication of poliovirus. accumulating evidence suggests that mammalian micrornas (mirnas), a class of noncoding rnas of 18 to 23 nucleotides (nt) with important regulatory roles in many cellular processes, participate in host antiviral defenses. however, the roles of mirnas in ev71 infection and pathogenesis are still unclear. here, hsa-mir-296-5p expression was significantly increased in ev71-infecte ... | 2013 | 23468506 |
| mda5 plays a crucial role in enterovirus 71 rna-mediated irf3 activation. | induction of type-i interferons (ifns), ifn-α/β, is crucial to innate immunity against rna virus infection. cytoplasmic retinoic acid-inducible gene i (rig-i)-like receptors, including rig-i and melanoma differentiation-associated gene 5 (mda5), are critical pathogen sensors for activation of type-i ifn expression in response to rna virus infection. mda5 is required for type-i ifn expression in mouse models in response to infection by picornaviruses, such as encephalomyocarditis virus (emcv) and ... | 2013 | 23650567 |
| itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein. | itraconazole (itz) is a well-known antifungal agent that also has anticancer activity. in this study, we identify itz as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus). we demonstrate that itz inhibits viral rna replication by targeting oxysterol-binding protein (osbp) and osbp-related protein 4 (orp4). consistently, osw-1, a specific osbp/orp4 antagonist, also inhibits enterovirus replication. knockdown of osbp inhibits virus replicati ... | 2015 | 25640182 |
| a conserved inhibitory mechanism of a lycorine derivative against enterovirus and hepatitis c virus. | enterovirus 71 (ev71) (picornaviridae family) and hepatitis c virus (hcv) (flaviviridae family) are the causative agents of human hand, foot, and mouth disease (hfmd) and hepatitis c, resulting in a severe pandemic involving millions of infections in the asia-pacific region and worldwide. the great impact of ev71 and hcv on public health highlights the need to further our understanding of the biology of these two viruses and develop effective therapeutic antivirals. here, we evaluated a total of ... | 2015 | 26596952 |
| coxsackievirus mutants that can bypass host factor pi4kiiiβ and the need for high levels of pi4p lipids for replication. | rna viruses can rapidly mutate and acquire resistance to drugs that directly target viral enzymes, which poses serious problems in a clinical context. therefore, there is a growing interest in the development of antiviral drugs that target host factors critical for viral replication, since they are unlikely to mutate in response to therapy. we recently demonstrated that phosphatidylinositol-4-kinase iiiβ (pi4kiiiβ) and its product phosphatidylinositol-4-phosphate (pi4p) are essential for replica ... | 2012 | 22945356 |
| sequence specificity for uridylylation of the viral peptide linked to the genome (vpg) of enteroviruses. | enteroviruses (ev) uridylylate a peptide, vpg, as the first step in their replication. vpgpupu, found free in infected cells, serves as the primer for rna elongation. the abilities of four polymerases (3d(pol)), from ev-species a-c, to uridylylate vpgs that varied by up to 60% of their residues were compared. each 3d(pol) was able to uridylylate all five vpgs using polya rna as template, while showing specificity for its own genome encoded peptide. all 3d(pol) uridylylated a consensus vpg repres ... | 2015 | 26074065 |
| development of novel vaccines against enterovirus-71. | the hand, foot and mouth disease is caused by a group of enteroviruses such as enterovirus 71 (ev-a71) and coxsackievirus cv-a5, cv-a8, and cv-a16. mild symptoms of ev-a71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. the lack of vaccines and antiviral drugs against ev-a71 highlights the urgency of developing preventive and treat ... | 2015 | 26729152 |
| pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates. | enterovirus 71 (ev71) has caused several epidemics of hand, foot and mouth diseases (hfmd) in asia and now is being recognized as an important neurotropic virus. effective medications and prophylactic vaccine against ev71 infection are urgently needed. based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated ev71 vaccine candidate has been developed and currently in human phase 1 clinical trial. | 2012 | 22529942 |
| production of ev71 vaccine candidates. | enterovirus 71 (ev71) is now recognized as an emerging neurotropic virus in asia and with coxsackie virus (cv) it is the other major causative agent of hand-foot-mouth diseases (hfmd). effective medications and/or prophylactic vaccines against hfmd are urgently needed. from a scientific (the feasibility of bioprocess, immunological responses and potency in animal challenge model) and business development (cost of goods) points of view, we in this review address and discuss the pros and cons of d ... | 2012 | 22992566 |
| immunological evaluation and comparison of different ev71 vaccine candidates. | enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are major causative agents of hand, foot, and mouth diseases (hfmds), and ev71 is now recognized as an emerging neurotropic virus in asia. effective medications and/or prophylactic vaccines against hfmd are not available. the current results from mouse immunogenicity studies using in-house standardized rd cell virus neutralization assays indicate that (1) vp1 peptide (residues 211-225) formulated with freund's adjuvant (cfa/ifa) elicited low v ... | 2012 | 23008736 |