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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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