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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
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
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
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
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
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
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
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
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
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
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
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
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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