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construction and characterization of an infectious cdna clone of echovirus 25.echovirus 25 (e-25) is a member of the enterovirus family and a common pathogen that induces hand, foot, and mouth disease (hfmd), meningitis, skin rash, and respiratory illnesses. in this study, we constructed and characterized an infectious full-length e-25 cdna clone derived from the xm0297 strain, which was the first subgenotype d6 strain isolated in xiamen, china. the 5'-untranslated regions (5'-utr), p3 (3a-3b, 3d) and p3 (3c) regions of this e-25 (xm0297) strain were highly similar to ev- ...201526004198
is a multivalent hand, foot, and mouth disease vaccine feasible?enterovirus a infections are the primary cause of hand, foot and mouth disease (hfmd) in infants and young children. although enterovirus 71 (ev-a71) and coxsackievirus a16 (cv-a16) are the predominant causes of hfmd epidemics worldwide, ev-a71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. hfmd is a serious health threat and economic burden across the asia-pacific region. inactivated ev-a71 vaccines have elicited protection again ...201526009802
enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated enterovirus a71 vaccine in jiangsu, china, 2012-2013.epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. an active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in jiangsu province from 2012 to 2013. fifty-nine infants were randomly selected from 522 non-ev-a71/cv-a16 hfmd patients. we collected 173 throat swabs and 174 rectal swabs from these infants. rt-pcr was used to ampl ...201526010334
seroepidemiology of coxsackievirus a6, coxsackievirus a16, and enterovirus 71 infections among children and adolescents in singapore, 2008-2010.coxsackieviruses a6 (cv-a6) and a16 (cv-a16) and enterovirus 71 (ev-a71) have caused periodic epidemics of hand, foot and mouth disease (hfmd) among children in singapore. we conducted a cross-sectional study to estimate the seroprevalence of these enteroviruses among singapore children and adolescents. the study was conducted between august 2008 and july 2010. it involved 700 singapore residents aged 1-17 years whose residual sera were obtained following the completion of routine biochemical in ...201526011735
characterization of the antibody response against ev71 capsid proteins in chinese individuals by neibm-elisa.human enterovirus 71 (ev71) has become the major pathogen of hand, foot, and mouth disease (hfmd) worldwide, while the anti-ev71 antibody responses other than neutralizing epitopes have not been characterized. in this study, ev71 capsid proteins vp1, vp3, vp0 and various vp1 antigens were constructed to analyze anti-ev71 response in severe hfmd cases, non-hfmd outpatient children and normal adults using a novel evolved immunoglobulin-binding molecule (neibm)-based elisa. the high prevalence of a ...201526023863
determinants of ev71 immunogenicity and protection against lethal challenge in a mouse model.circulating enterovirus 71 (ev71)-associated hand, foot, and mouth disease (hfmd) is a major public health problem in the asian-pacific region. an ev71 vaccine for hfmd prevention is currently being developed. however, viral determinants that could influence the vaccine's efficacy have not been well characterized. in this study, we isolated and characterized several ev71 strains that are currently circulating in northern and southern china. we determined that vp1 variation is a major determinant ...201526025091
epidemiological characteristics and influential factors of hand, foot and mouth disease (hfmd) reinfection in children in anhui province.hand, foot and mouth disease (hfmd) is an acute contagious condition caused by a spectrum of human enteroviruses. hfmd reinfection is common in the absence of cross-protection from other virus subtypes. this study focused on reinfection in children in anhui province, china between 2008 and 2013 using surveillance system data. we classified 8960 cases as reinfected, corresponding to a rate of 2·02%. the reinfection rate was higher in boys than in girls [odds ratio (or) 1·27, 95% confidence interv ...201626027435
immunogenicity and protective efficacy of an ev71 virus-like particle vaccine against lethal challenge in newborn mice.enterovirus 71(ev71) has caused severe epidemics of hand, foot and mouth disease (hfmd) in the asia pacific in recent years, particularly in infants and pre-school children. it has become a serious public health threat, as currently there are no approved vaccines or antiviral drugs for ev71 infection. many ev71 vaccines have been under development worldwide, however the main focus is inactivated ev71 vaccines. for example, the inactivated ev71 vaccine has recently finished phase iii clinical tri ...201526036916
enterovirus 71 infection in children with hand, foot, and mouth disease in shanghai, china: epidemiology, clinical feature and diagnosis.in 2012 a large outbreak of hand, foot, and mouth disease (hfmd) widely spread over china, causing more than 2 million cases and 567 deaths. our purpose was to characterize the major pathogens responsible for the 2012 hfmd outbreak and analyze the genetic characterization of the enterovirus 71 (ev71) strains in shanghai; also, to analyze the dynamic patterns of neutralizing antibody (nab) against ev71 and evaluate the diagnostic value of several methods for clinical detection of ev71.201526036928
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 ...201326038441
ev71-infected cd14(+) cells modulate the immune activity of t lymphocytes in rhesus monkeys.preliminary studies of the major pathogen enterovirus 71 (ev71), a member of the picornaviridae family, have suggested that ev71 may be a major cause of fatal hand, foot and mouth disease cases. currently, the role of the pathological changes induced by ev71 infection in the immunopathogenic response remains unclear. our study focused on the interaction between this virus and immunocytes and indicated that this virus has the ability to replicate in cd14(+) cells. furthermore, these ev71-infected ...201326038477
neutralizing antibody responses to enterovirus and adenovirus in healthy adults in china.hand, foot and mouth disease (hfmd) is an important public health problem that has emerged over the past several years. hfmd predominantly infects children under seven years old and occasionally causes severe disease in adults. among the enteroviruses, enterovirus 71 (ev71) and coxsackievirus 16 (ca16) are the major causative agents of hfmd. in addition, adenovirus cocirculates with enterovirus and has become a possible additional pathogenic factor for hfmd in some cases. here, we have investiga ...201426038738
a neonatal gnotobiotic pig model of human enterovirus 71 infection and associated immune responses.vaccine development and pathogenesis studies for human enterovirus 71 are limited by a lack of suitable animal models. here, we report the development of a novel neonatal gnotobiotic pig model using the non-pig-adapted neurovirulent human enterovirus 71 strain bj110, which has a c4 genotype. porcine small intestinal epithelial cells, peripheral blood mononuclear cells and neural cells were infected in vitro. oral and combined oral-nasal infection of 5-day-old neonatal gnotobiotic pigs with 5×10( ...201426038741
receptors for enterovirus 71.enterovirus 71 (ev71) is one of the major causative agents of hand, foot and mouth disease (hfmd). occasionally, ev71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. several molecules act as cell surface receptors that stimulate ev71 infection, including scavenger receptor b2 (scarb2), p-selectin glycoprotein ligand-1 (psgl-1), sialylated glycan, heparan sulfate and annexin ii (anx2). scarb2 plays critica ...201426038749
the approved pediatric drug suramin identified as a clinical candidate for the treatment of ev71 infection-suramin inhibits ev71 infection in vitro and in vivo.enterovirus 71 (ev71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. there is an urgent unmet medical need for new pharmaceutical agents to control ev71 infections. using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked ev71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. moreover, we de ...201426038755
phylogenetic analysis of the major causative agents of hand, foot and mouth disease in suzhou city, jiangsu province, china, in 2012-2013.hand, foot and mouth disease (hfmd) is a serious public health problem that has emerged over the past several decades. pathogen detection by the chinese national hfmd surveillance system has focused mainly on enterovirus 71 (ev71) and coxsackievirus a16 (ca16). therefore, epidemiological information regarding the other causative enteroviruses is limited. to identify the pandemic enterovirus in suzhou, jiangsu province, china, clinical samples from patients with hfmd were collected from 2012 to 2 ...201526038764
monoclonal neutralizing antibodies against ev71 screened from mice immunized with yeast-produced virus-like particles.periodic outbreaks of hand, foot and mouth disease (hfmd) occur in children under 5 years old, and can cause death in some cases. the c4 strain of enterovirus 71 (ev71) is the main pathogen that causes hfmd in china. although no drugs against ev71 are available, some studies have shown that candidate vaccines or viral capsid proteins can produce anti-ev71 immunity. in this study, female babl/c mice (6-8 weeks old) were immunized with virus-like particles (vlps) of ev71 produced in yeast to scree ...201526040893
yakammaoto inhibits enterovirus 71 infection by reducing viral attachment, internalization, replication, and translation.enterovirus 71 (ev71) can cause central nervous system infections with mortality and neurologic sequelae. at present, there is no effective therapeutic modality for ev71 infection. the infection is more common in families with poor socioeconomic status. therefore, finding a readily available, cost-effective therapeutic modality would be very helpful to these socioeconomically disadvantaged families. yakammaoto is a cheap and readily available traditional prescription that is proven to have antiv ...201526043408
validation and utilization of an internally controlled multiplex real-time rt-pcr assay for simultaneous detection of enteroviruses and enterovirus a71 associated with hand foot and mouth disease.hand foot and mouth disease (hfmd) is a disease of public health importance across the asia-pacific region. the disease is caused by enteroviruses (evs), in particular enterovirus a71 (ev-a71). in ev-a71-associated hfmd, the infection is sometimes associated with severe manifestations including neurological involvement and fatal outcome. the availability of a robust diagnostic assay to distinguish ev-a71 from other evs is important for patient management and outbreak response.201526050791
cytokine responses and correlations thereof with clinical profiles in children with enterovirus 71 infections.severe complications associated with ev71 infections caused many infants death. however, the pathogenesis of ev71 infection in the severe cases remained poorly understood.201526058678
molecular epidemiology of an outbreak of hand, foot, and mouth disease associated with subgenotype c4a of enterovirus a71 in nanchang, china in 2014.an outbreak of hand, foot, and mouth disease was reported through hospital-based surveillance in nanchang, china in 2014. a total of 244 cases were reported, 176 (72.1%) cases were tested positive for enteroviruses by direct reverse transcription-polymerase chain reaction, in which enterovirus a71 (ev-a71), coxsackievirus a16 (cv-a16), and untyped enteroviruses (uev) accounted for 84.1%, 3.4%, and 12.5%, respectively. in this outbreak, children under 5 years old constituted more than 98% of the ...201526058813
exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.the enterovirus genus of the picornaviridae is represented by several viral pathogens that are associated with human disease, namely poliovirus 1, enterovirus 71 and rhinoviruses. enterovirus 71 has been associated with encephalitis, while rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of rhinovirus replication.201526071135
phage display-derived cross-reactive neutralizing antibody against enterovirus 71 and coxsackievirus a16.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are members of the picornaviridae family and are considered the main causative agents of hand, foot and mouth disease (hfmd). in recent decades large hfmd outbreaks caused by ev71 and cva16 have become significant public health concerns in the asia-pacific region. vaccines and antiviral drugs are unavailable to prevent ev71 and cva16 infection. in the current study, a chimeric antibody targeting a highly conserved peptide in the ev71 vp4 prote ...201626073737
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 ...201526074065
anti-viral and cytotoxic norbisabolane sesquiterpenoid glycosides from phyllanthus emblica and their absolute configurations.in an effort to identify anti-viral and cytotoxic compounds from phyllanthus spp., 14 highly oxygenated norbisabolane sesquiterpenoids, phyllaemblicins h1-h14, were isolated from the roots of phyllanthus emblica linn, along with phyllaemblicins b and c and glochicoccinoside d. their structures were determined on the basis of detailed spectroscopic analysis and chemical methods. determination of absolute configurations of these compounds was facilitated by theoretical calculations of electronic c ...201526074492
[detection of cerebrospinal fluid anti-enterovirus 71 igm in children with severe hand, food and mouth disease induced by enterovirus 71 infection and its clinical significance].to detect the anti-enterovirus 71 (ev71) igm level in cerebrospinal fluid (csf) of children with severe hand, foot and mouth disease (hfmd) induced by ev71 and then analyze the relationships among the igm antibody levels, csf routine examination and patients' clinical features, and thus to evaluate the clinical significance of anti-ev71 igm as a new indicator for early diagnosis of children with severe hfmd induced by ev71.201526080665
[research progress on seroepidemiological study of enterovirus 71 and coxsackievirus a16 infection among children].most common causative agents for hand, foot and mouth disease (hfmd) are enterovirus 71 (ev-a71) and coxsackievirus a16 (cv-a16). the symptomatic and asymptomatic cases could transmit the disease in population. many sero-epidemiological surveys were launched to estimate the sero-incidence of ev-a71 and cv-a16 enterovirus, the susceptibility of different sub-population, and to observe the dynamics of neutralizing antibody. a literature search of sero-epidemiological study focused on ev-a71 or cv- ...201526081408
phylodynamics of enterovirus a71-associated hand, foot, and mouth disease in viet nam.enterovirus a71 (ev-a71) is a major cause of hand, foot, and mouth disease (hfmd) and is particularly prevalent in parts of southeast asia, affecting thousands of children and infants each year. revealing the evolutionary and epidemiological dynamics of ev-a71 through time and space is central to understanding its outbreak potential. we generated the full genome sequences of 200 ev-a71 strains sampled from various locations in viet nam between 2011 and 2013 and used these sequence data to determ ...201526085170
hand-foot-and-mouth disease: a new look at a classic viral rash.hand-foot-and-mouth disease (hfmd) is a common cause of viral rash in children with classic skin findings which are easily recognized by pediatricians. recently, several atypical cutaneous manifestations of hfmd have been described. awareness of these patterns may lead providers to appropriate diagnosis and management. this review also highlights the epidemiological patterns of more virulent strains and emerging research in disease prevention.201526087425
prevalence of coxsackievirus a6 and enterovirus 71 in hand, foot and mouth disease in nanjing, china in 2013.although hand, foot and mouth disease (hfmd) has been strongly associated with enterovirus 71 (ev71), coxsackievirus a16 (cva16) and other enteroviruses, studies regarding coxsackievirus a6 (cva6) infection in hfmd are limited. the aim of this study was to identify the major etiological agents causing hfmd in nanjing in 2013 and explore the clinical and genetic characteristics of the prevalent enterovirus (ev) types in hfmd.201526090576
antiviral potential of a novel compound cw-33 against enterovirus a71 via inhibition of viral 2a protease.enterovirus a71 (ev-a71) in the picornaviridae family causes hand-foot-and-mouth disease, aseptic meningitis, severe central nervous system disease, even death. ev-a71 2a protease cleaves type i interferon (ifn)-α/β receptor 1 (ifnar1) to block ifn-induced jak/stat signaling. this study investigated anti-ev-a7l activity and synergistic mechanism(s) of a novel furoquinoline alkaloid compound cw-33 alone and in combination with ifn-β anti-ev-a71 activities of cw-33 alone and in combination with if ...201526090728
an enterovirus 71 strain causes skeletal muscle damage in infected mice.to study the target organs for enterovirus 71 (ev71) in infected suckling mice.201526097530
[enterovirus sequencing as a new approach to the laboratory diagnosis for clinical and epidemiological purposes].introducing enterovirus sequencing as an advanced approach to classify the viruses isolated according to the novel nomenclature and to characterize isolates in detail.201526099615
ocular pathology: role of emerging viruses in the asia-pacific region-a review.the role of viral infections in ocular pathology varies greatly, involving all the components of the eye. some viruses like herpes simplex, herpes zoster, adenovirus, enterovirus 70, influenza virus, human immunodeficiency virus, and cytomegalovirus are well-known for their role in ocular pathology. in recent years, emerging and resurging viral infections represent an important public health problem. the asia-pacific region has witnessed a number of pandemic and epidemic outbreaks caused by thes ...201726107917
[mitochondrial injury in enterovirus 71-infected vero cells and its mechanism].to investigate the mitochondrial injury in enterovirus 71 (ev71)-infected vero cells and explore the possible mechanism.201526111685
coxsackievirus a6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide.enterovirus 71 (ev71) and coxsackievirus a16 (ca16) are the predominant pathogens causing outbreaks of hand, foot and mouth disease (hfmd) worldwide. other human enterovirus a (hev-a) serotypes tend to cause only sporadic hfmd cases. however, since a hfmd caused by coxsackievirus a6 broke out in finland in 2008, ca6 has been identified as the responsible pathogen for a series of hfmd outbreaks in europe, north america and asia. because of the severity of the clinical manifestations and the under ...201526112307
reciprocal regulation between enterovirus 71 and the nlrp3 inflammasome.enterovirus 71 (ev71) is the major etiological agent of hand, foot, and mouth disease (hfmd). early studies showed that ev71-infected patients with severe complications exhibited elevated plasma levels of il-1β, indicating that ev71 may activate inflammasomes. our current study demonstrates that the nlrp3 inflammasome plays a protective role against ev71 infection of mice in vivo. ev71 replication in myeloid cells results in the activation of the nlrp3 inflammasome and secretion of il-1β. conver ...201526119741
ma104 cell line presents characteristics suitable for enterovirus a71 isolation and proliferation.enterovirus a71 (ev-a71), one of the most important causative agents of hand, foot and mouth disease (hfmd) in children, can lead to severe clinical outcomes, even death. however, the infection spectrum of ev-a71 in different cell lines remains unknown. therefore, in this study, the biological characteristics of ev-a71 subgroup c4 in different cell lines were investigated. to this end, the infectivity of ev-a71jinan1002 isolated from children with severe hfmd was assessed in 18 different host ce ...201526138857
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 ...026158689
socioeconomic burden of hand, foot and mouth disease in children in shanghai, china.in the near future, the inactivated enterovirus 71 (ev71) vaccine is expected to become available on the market in china. since ev71 is a major cause of hand, foot and mouth disease (hfmd), the vaccine is expected to significantly reduce the number of cases, as well as the detrimental economic effect of the disease. however, for a national vaccination strategy to be developed, policy-makers need more information on the socioeconomic burden of ev71 hfmd infection. based on the 2011 population dat ...201626159305
[research into the pathogenicity of enterovirus 71].enterovirus 71 (ev71) is a major causative agent of hand, foot and mouth disease (hfmd). belongs to family picornaviridae, genus enterovirus, species a. ev71 infection usually affects subjects aged <5 years. hfmd caused by ev71 infection is usually mild in children. however, in some cases ev71 infection can lead to severe neurogenic disease and even death. ev71 infection has caused epidemic worldwide (especially in the asia pacific). hfmd caused by ev71 has become a major public-health prol lem ...201526164947
[molecular mechanism of action of hnrnp k and rtn3 in the replication of enterovirus 71].enterovirus 71 (ev71) is a neurotropic pathogen that can induce hand, foot and mouth disease in children. there is an appreciable mortality rate after ev71 infections. the mechanism of action of ev71 replication is not known. recent work has identified some of cell factors of the host that participate in the synthesis of the rna and proteins of ev71 (e.g., hnrnp k, reticulon 3 (rtn 3)). in that work, researchers used a competitive assay to show that hnrnp k can interact with ev71 5' utr, which i ...201526164948
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 ...026166120
broad protection with an inactivated vaccine against primary-isolated lethal enterovirus 71 infection in newborn mice.circulating enterovirus 71 (ev-a71)-associated hand, foot, and mouth disease is on the rise in the asian-pacific region. although animal models have been developed using mouse-adapted ev-a71 strains, mouse models using primary ev-a71 isolates are scarce. lethal animal models with circulating ev-a71 infection would contribute to studies of pathogenesis as well as vaccine development and evaluation.201526169371
the role of vp1 amino acid residue 145 of enterovirus 71 in viral fitness and pathogenesis in a cynomolgus monkey model.enterovirus 71 (ev71), a major causative agent of hand, foot, and mouth disease, occasionally causes severe neurological symptoms. we identified p-selectin glycoprotein ligand-1 (psgl-1) as an ev71 receptor and found that an amino acid residue 145 in the capsid protein vp1 (vp1-145) defined psgl-1-binding (pb) and psgl-1-nonbinding (non-pb) phenotypes of ev71. however, the role of psgl-1-dependent ev71 replication in neuropathogenesis remains poorly understood. in this study, we investigated vir ...201526181772
development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human enterovirus-71 vaccine encapsulated carrier.this study introduces a new approach for enhancing immunity toward mucosal vaccines. hev71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific iga & igg levels and viral neutralizing antibody titers. the antibody responses induced in rabbits by the different formulations delivered by a sing ...201526186664
quinolizidine alkaloids reduced mortality in ev71-infected mice by compensating for the levels of t cells.recent outbreak of hand, foot and mouse disease caused by enterovirus 71 is a serious threat to infants and children in asia-pacific countries. no vaccines or antiviral therapies are available against this infection. in this study, we found that quinolizidine alkaloids could improve the levels of t cells in mice. the structure-activity relationships demonstrated that the oxidation and double bonds are important for the excellent potency. oxysophocarpine, the most effective compound of six quinol ...201526189894
optimization and characterization of candidate strain for coxsackievirus a16 inactivated vaccine.coxsackievirus a16 (ca16) and enterovirus 71 (ev71), both of which can cause hand, foot and mouth disease (hfmd), are responsible for large epidemics in asian and pacific areas. although inactivated ev71 vaccines have completed testing in phase iii clinical trials in mainland china, ca16 vaccines are still under development. a vero cell-based inactivated ca16 vaccine was developed by our group. screening identified a ca16 vaccine strain (cc024) isolated from hfmd patients, which had broad cross- ...201526193302
enterovirus a71 meningoencephalitis outbreak, rostov-on-don, russia, 2013.seventy-eight cases of enterovirus infection, including 25 neuroinfections, occurred in rostov-on-don, russia, during may-june 2013. the outbreak was caused by an enterovirus a type 71 (ev-a71) subgenotype c4 lineage that spread to neighboring countries from china ≈3 years earlier. enterovirus associated neuroinfection may emerge in areas with a preceding background circulation of ev-a71 with apparently asymptomatic infection.201526196217
nuclear protein sam68 interacts with the enterovirus 71 internal ribosome entry site and positively regulates viral protein translation.enterovirus 71 (ev71) recruits various cellular factors to assist in the replication and translation of its genome. identification of the host factors involved in the ev71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. in this study, we demonstrated that the cellular factor 68-kda src-associated protein in mitosis (sam68) acts as an internal ribosome entry site (ires) trans-ac ...201526202240
unusual skin manifestation of hand, foot and mouth disease associated with coxsackievirus a6: cases report.hand, food, and mouth disease (hfmd) is a highly contagious disease caused by enteroviruses infection. it is a health problem in young children under 5 years of age worldwide. the common causative agents are coxsackievirus a 16 (ca16) and enterovirus 71 (ev71). in recent years, coxsackievirus a6 (ca6) has emerged to be one of the major etiologic agents of hfmd worldwide including in thailand.201526203408
human enterovirus nonstructural protein 2catpase functions as both an rna helicase and atp-independent rna chaperone.rna helicases and chaperones are the two major classes of rna remodeling proteins, which function to remodel rna structures and/or rna-protein interactions, and are required for all aspects of rna metabolism. although some virus-encoded rna helicases/chaperones have been predicted or identified, their rna remodeling activities in vitro and functions in the viral life cycle remain largely elusive. enteroviruses are a large group of positive-stranded rna viruses in the picornaviridae family, which ...201526218680
australian national enterovirus reference laboratory annual report, 2013.australia conducts surveillance for cases of acute flaccid paralysis (afp) in children less than 15 years of age as the main method to monitor its polio-free status in accordance with the world health organization (who) recommendations. cases of afp in children are notified to the australian paediatric surveillance unit or the paediatric active enhanced disease surveillance system and faecal specimens are referred for virological investigation to the national enterovirus reference laboratory. in ...201526234257
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 ...201526243660
[expression of ev71-vp1, psgl-1 and scarb2 in tissues of infants with brain stem encephalitis].to understand the correlation of enterovirus 71 (ev71), p-selectin glycoprotein ligand-1 (psgl-1), and scavenger receptor b2 (scarb2) and to explore the possible pathway and mechanism of ev71 infection by observing the expression of ev71, psgl-1 and scarb2 in tissues of infants with brain stem encephalitis.201526245084
enterovirus71 virus-like particles produced from insect cells and purified by multistep chromatography elicit strong humoral immune responses in mice.the study aims to develop a novel multistep chromatographic purification process for human enterovirus71 virus-like particles (vlps) produced from insect cells (sf9) infected with recombinant baculovirus.201526248815
norepinephrine and epinephrine enhanced the infectivity of enterovirus 71.enterovirus 71 (ev71) infections may be associated with neurological complications, including brainstem encephalitis (be). severe ev71 be may be complicated with autonomic nervous system (ans) dysregulation and/or pulmonary edema (pe). ans dysregulation is related to the overactivation of the sympathetic nervous system, which results from catecholamine release.201526252639
epidemiologic and etiologic characteristics of hand, foot, and mouth disease in chongqing, china between 2010 and 2013.hand, foot, and mouth disease (hfmd) has become very common in children, with widespread occurrence across china. the aim of this study was to investigate the epidemiologic and etiologic characteristics of hfmd, including etiologic variations in chongqing, china. an epidemiologic investigation was based on 3,472 patients who presented with hfmd manifestations and were admitted at the children's hospital of chongqing medical university between 2010 and 2013. fecal specimens from 830 patients were ...201626255857
replication and inhibitors of enteroviruses and parechoviruses.the enterovirus (ev) and parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, ev-a71, ev-d68, and human parechoviruses (hpev). they cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. at the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all evs and hpevs due to the great number o ...201526266417
structures of coxsackievirus a16 capsids with native antigenicity: implications for particle expansion, receptor binding, and immunogenicity.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are the primary causes of the epidemics of hand-foot-and-mouth disease (hfmd) that affect more than a million children in china each year and lead to hundreds of deaths. although there has been progress with vaccines for ev71, the development of a cva16 vaccine has proved more challenging, and the ev71 vaccine does not give useful cross-protection, despite the capsid proteins of the two viruses sharing about 80% sequence identity. the structur ...201526269176
construction and characterization of infectious cdna clones of enterovirus 71 (ev71). 201526271283
immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates.a vaccine against human enterovirus 71 (ev-a71) is urgently needed to combat outbreaks of ev-a71 and in particular, the serious neurological complications that manifest during these outbreaks. in this study, an ev-a71 virus-like-particle (vlp) based on a b5 subgenogroup (ev-a71-b5 vlp) was generated using an insect cell/baculovirus platform. biochemical analysis demonstrated that the purified vlp had a highly native procapsid structure and initial studies in vivo demonstrated that the vlps were ...201526271825
understanding enterovirus 71 neuropathogenesis and its impact on other neurotropic enteroviruses.enterovirus a71 (ev-a71) belongs to the species group a in the enterovirus genus within the picornaviridae family. ev-a71 usually causes self-limiting hand, foot and mouth disease or herpangina but rarely causes severe neurological complications such as acute flaccid paralysis and encephalomyelitis. the pathology and neuropathogenesis of these neurological syndromes is beginning to be understood. ev-a71 neurotropism for motor neurons in the spinal cord and brainstem, and other neurons, is mainly ...201526276025
inactivated enterovirus 71 vaccine produced by 200-l scale serum-free microcarrier bioreactor system provides cross-protective efficacy in human scarb2 transgenic mouse.epidemics and outbreaks caused by infections of several subgenotypes of ev71 and other serotypes of coxsackie a viruses have raised serious public health concerns in the asia-pacific region. these concerns highlight the urgent need to develop a scalable manufacturing platform for producing an effective and sufficient quantity of vaccines against deadly enteroviruses. in this report, we present a platform for the large-scale production of a vaccine based on the inactivated ev71(e59-b4) virus. the ...201526287531
the fecal virome of children with hand, foot, and mouth disease that tested pcr negative for pathogenic enteroviruses.hand, foot, and mouth disease (hfmd) affects infant and young children. a viral metagenomic approach was used to identify the eukaryotic viruses in fecal samples from 29 thai children with clinical diagnosis of hfmd collected during the 2012 outbreak. these children had previously tested negative by pcr for enterovirus 71 and coxsackievirus a16 and a6. deep sequencing revealed nine virus families: picornaviridae, astroviridae, parvoviridae, caliciviridae, paramyxoviridae, adenoviridae, reovirida ...201526288145
type i interferons triggered through the toll-like receptor 3-trif pathway control coxsackievirus a16 infection in young mice.coxsackievirus a16 (cva16) is one of the major etiological agents of hand, foot, and mouth disease (hfmd) in children. the host defense mechanisms against cva16 infection remain almost entirely unknown. unlike previous observations with enterovirus 71 (ev71) infection, here we show that gamma interferon (ifn-γ) or invariant nk t cell deficiency does not affect disease development or the survival of cva16-infected mice. in contrast, type i interferon receptor deficiency resulted in the developmen ...201526292317
the antiviral effect of baicalin on enterovirus 71 in vitro.baicalin is a flavonoid compound extracted from scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. however, the antiviral effect of baicalin on enterovirus 71 (ev71) is still unknown. in this study, we found that baicalin showed inhibitory activity on ev71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. the expressions of ev71/3d mrna and polymerase were significantly blocked by ...201526295407
hexon-modified recombinant e1-deleted adenoviral vectors as bivalent vaccine carriers for coxsackievirus a16 and enterovirus 71.hand, foot and mouth disease (hfmd) is a major public health concern in asia; more efficient vaccines against hfmd are urgently required. adenoviral (ad) capsids have been used widely for the presentation of foreign antigens to induce specific immune responses in the host. here, we describe a novel bivalent vaccine for hfmd based on the hexon-modified, e1-deleted chimpanzee adenovirus serotype 68 (adc68). the novel vaccine candidate was generated by incorporating the neutralising epitope of coxs ...201526296491
intrinsic apoptosis and proinflammatory cytokines regulated in human astrocytes infected with enterovirus 71.enterovirus 71 (ev71) has emerged as a clinically important neurotropic virus following poliovirus eradication. however, the mechanism of ev71-induced neurological manifestation remains largely unclear. in this study, we showed that human astrocytes were susceptible to ev71 and viral rna was first detected at 12 h post-infection (p.i.), whilst viral proteins were detected at 36 h p.i. ev71-infected astrocytes underwent apoptosis, in which cytochrome c was released from mitochondria to the cytoso ...201526296773
clinical features for mild hand, foot and mouth disease in china.mild hand, foot and mouth disease (hfmd) is at a critical stage owing to its ease of communicability and a higher risk of developing severe complications and death. clinical diagnosis of mild hfmd was made by the presenting symptoms and signs (symptoms in brief) alone. we aim to evaluate the frequencies of symptoms in a retrospective case series study.201526302092
complete genome sequence analysis of enterovirus 71 isolated from children with hand, foot, and mouth disease in thailand, 2012-2014.the complete genomic sequences of 14 enterovirus 71 (ev71) strains isolated from children with hand, foot, and mouth disease in thailand from 2012 to 2014 were determined and compared to enterovirus group a prototypes. phylogenetic analysis revealed that 13 strains resembled the b5 subgroup, while one strain from a fatal case designated tha_1219 belonged to the c4 subgroup. similarity plot and bootscan analyses suggested that tha_1219 underwent recombination in the p2 and p3 regions. full-genome ...201526303899
association of chemotactic chemokine ligand 5 polymorphisms with the risk of developing severe enterovirus 71 infection.respiratory damage is a main manifestation of severe enterovirus 71 (ev71) infection. polymorphisms of -403g/a (rs2107538), -28c/g (rs2280788), and in1.1t/c (rs2280789) in chemotactic chemokine ligand 5 (ccl5) have linked with many respiratory diseases. in this study, we explored the possible correlation of ccl5 polymorphisms with severe ev71 infection. blood samples were obtained from 87 children hospitalized for ev71 infection. fifty-seven healthy children were enrolled as asymptomatic control ...201526304916
fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from wenzhou, china.although hand, foot, and mouth disease (hfmd) is a major public concern in china, the prevalence and clinical symptoms associated with the different agents of hfmd in this country remain poorly understood.201526305816
analysis of ev71 infection progression using triple-silac-based proteomics approach.enterovirus 71 (ev71), a member of picornaviridae, causes severe neurological and systemic illness in children. to better understand the virus-host cell interactions, we performed a triple-silac-based quantitative proteomics study monitoring host cell proteome changes after ev71 infection. based on the quantitative data for more than 4100 proteins, ∼17% of the proteins were found as significantly changed (p<0.01) at either 8 or 20 hours post infection. five biological processes and seven protein ...201526306425
[the etiological and clinical characteristics of hospitalized children with hand, foot and mouth disease in beijing in 2013].to investigate the etiology of hand, foot and mouth disease (hfmd) in beijing during 2013, and study the clinical characteristics of hfmd caused by the main serotypes of enterovirus in the study.201526310558
co-infection of enterovirus 71 and staphylococcus aureus in a 6-month-old male infant. 201526322107
antiviral activity of chrysin derivatives against coxsackievirus b3 in vitro and in vivo.chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (ev71) by suppressing viral 3c protease (3c(pro)) activity. in the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus b3 (cvb3), which belongs to the same genus (enterovirus) as ev71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. we found that chrysin showed antiviral activity against cvb3 at 10 μm, but exhibited mild ...201526336587
mapping enterovirus a71 antigenic determinants from viral evolution.human enterovirus a71 (ev-a71) belongs to the enterovirus a species in the picornaviridae family. several vaccines against ev-a71, a disease causing severe neurological complications or even death, are currently under development and being tested in clinical trials, and preventative vaccination programs are expected to start soon. to characterize the potential for antigenic change of ev-a71, we compared the sequences of two antigenically diverse genotype b4 and b5 strains of ev-a71 and identifie ...201526339057
the role of micrornas in enteroviral infections.the genus enterovirus, a member of the picornavirus family, are rna viruses that can cause poliomyelitis, hand-food-mouth disease, viral meningitis or meningoencephalitis, viral myocarditis and so on. micrornas are a class of highly conserved, small noncoding rnas recognized as important regulators of gene expression. recent studies found that micrornas play a significant role in the infection of enterovirus, such as enterovirus 71, coxsackievirus b3 and other enterovirus. enteroviral infection ...201526342975
global quantitative proteomic analysis of human glioma cells profiled host protein expression in response to enterovirus type 71 infection.enterovirus 71 (ev71) is one of the leading causes of hand, foot and mouth disease with neurological complications in some cases. to study the pathogenesis of ev71 infection, large-scale analyses of ev71 infected cells have been performed. however, most of these studies employed rhabdomyosarcoma (rd) cells or used transcriptomic strategy. here, we performed silac-based quantitative proteomic analysis of ev71-infected u251 cells, a human glioma cell line. a total of 3125 host proteins were quanti ...201526350028
a severe case of co-infection with enterovirus 71 and vaccine-derived poliovirus type ii.enterovirus 71 (ev71) is often identified as the primary pathogen that directly leads to severe cases of hfmd, whereas the association between other enteroviruses and ev71 infection remains largely unclear. here we report a rare case of a 5-year-old boy co-infected with ev71 and vaccine-derived poliovirus (vdpv) type ii, which were identified based on pcr and sequence analysis results and clinical symptoms and were characterized on ct. we determined that the ev71 strain belongs to the c4 subtype ...201526361010
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.201526362772
development of a specific latex agglutination test to detect antibodies of enterovirus 71.a latex agglutination test (lat) was developed for the rapid detection of antibodies against the vp1 or vp1 proteins of enterovirus 71 (ev71). the proteins of interest including prokaryotically expressed vp1 and two strains of anti-vp1 monoclonal antibody (mcab) against ev71 were covalently linked to carboxylated latex using ethyl-dimethyl-amino-propyl carbodiimide (edc) to prepare sensitized latex beads. lat was evaluated by an enzyme-linked immunosorbent assay (elisa) as a reference test. the ...201526363276
tia-1 and tiar interact with 5'-utr of enterovirus 71 genome and facilitate viral replication.enterovirus 71 is one of the major causative pathogens of hfmd in children. upon infection, the viral rna is translated in an ires-dependent manner and requires several host factors for effective replication. here, we found that t-cell-restricted intracellular antigen 1 (tia-1), and tia-1 related protein (tiar) were translocated from nucleus to cytoplasm after ev71 infection and localized to the sites of viral replication. we found that tia-1 and tiar can facilitate ev71 replication by enhancing ...201526363455
seroprevalence of enterovirus 71 antibody among children in china: a systematic review and meta-analysis.hand, foot and mouth disease mostly affects children and carries a substantial disease burden in the western pacific region. enterovirus 71 (ev71) is the most virulent causative agent, and a monovalent vaccine against ev71 will soon become commercially available in china. an improved understanding of ev71 epidemiology would aid policy decisions regarding childhood immunization in china. we aimed to assess and summarize information to date from individual seroepidemiologic studies of ev71 in main ...201526368058
anti-enterovirus 71 agents of natural products.this review, with 42 references, presents the fascinating area of anti-enterovirus 71 natural products over the last three decades for the first time. it covers literature published from 2005-2015 and refers to compounds isolated from biogenic sources. in total, 58 naturally-occurring anti-ev71 compounds are recorded.201526370955
basic reproduction number of coxsackievirus type a6 and a16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in singapore, a tropical city-state.coxsackievirus a6 (cv-a6), coxsackievirus a16 (cv-a16) and enterovirus 71 (ev-a71) were the major enteroviruses causing nationwide hand, foot and mouth disease (hfmd) epidemics in singapore in the last decade. we estimated the basic reproduction number (r 0) of these enteroviruses to obtain a better understanding of their transmission dynamics. we merged records of cases from hfmd outbreaks reported between 2007 and 2012 with laboratory results from virological surveillance. r 0 was estimated ba ...201626374168
rapid next-generation sequencing of dengue, ev-a71 and rsv-a viruses.accurate characterisation of viral strains constitutes a crucial objective for the management of modern virus collections. next-generation sequencing (ngs) provides technical solution for fast and cost-effective full genome sequencing. here, we report protocols for rapid full-genome characterisation of rna viruses of medical importance: dengue virus, enterovirus a71 and respiratory syncytial virus a, based on a specific amplification step followed by ngs-sequencing. a subset of full-length genom ...201526376168
immunity and clinical efficacy of an inactivated enterovirus 71 vaccine in healthy chinese children: a report of further observations.to investigate the long-term effects on immunity of an inactivated enterovirus 71 (ev71) vaccine and its protective efficacy.201526381232
enterovirus 71 2c protein inhibits nf-κb activation by binding to rela(p65).viruses evolve multiple ways to interfere with nf-κb signaling, a key regulator of innate and adaptive immunity. enterovirus 71 (ev71) is one of primary pathogens that cause hand-foot-mouth disease. here, we identify rela(p65) as a novel binding partner for ev71 2c protein from yeast two-hybrid screen. by interaction with ipt domain of p65, 2c reduces the formation of heterodimer p65/p50, the predominant form of nf-κb. we also show that picornavirus 2c family proteins inhibit nf-κb activation an ...201526394554
enterovirus 71 infection caused neuronal cell death and cytokine expression in cultured rat neural cells.fatal enterovirus type-71 (ev71) cases are associated with central nervous system infection characterized by inflammatory cell infiltration and activation, cytokine overproduction, and neuronal cell death. although ev71 antigen has been detected in neurons and glia, the molecular mechanisms underlying ev71-associated neuroinflammation and neuronal cell death are not fully understood. using cultured rodent neural cell models, we found that ev71 infection preferentially caused cell death in neuron ...201526399559
antibodies to p-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.p-selectin glycoprotein ligand-1 (psgl-1) has been proved to serve as the functional receptor for enterovirus 71 (ev71). we found the abundant expression of psgl-1 on monocyte-derived dendritic cells (mddcs). however, we have previously demonstrated that mddcs did not support efficient replication of ev71. dendritic cells (dcs) have been described to be subverted by various viruses including ev71 for viral dissemination, we thus explore the potential contribution of psgl-1 on dc-mediated ev71 tr ...201526399965
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 ...201526401034
characterizing enterovirus 71 and coxsackievirus a16 virus-like particles production in insect cells.enterovirus 71 (ev71) and coxsackievirus a16 (cva16) are two viruses commonly responsible for hand, foot and mouth disease (hfmd) in children. the lack of prophylactic or therapeutic measures against hfmd is a major public health concern. insect cell-based ev71 and cva16 virus-like particles (vlps) are promising vaccine candidates against hfmd and are currently under development. in this paper, the influence of insect cell line, incubation temperature, and serial passaging effect and stability o ...201626410190
similar protective immunity induced by an inactivated enterovirus 71 (ev71) vaccine in neonatal rhesus macaques and children.during the development of enterovirus 71 (ev71) inactivated vaccine for preventing human hand, foot and mouth diseases (hfmd) by ev71 infection, an effective animal model is presumed to be significant and necessary. our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of hfmd, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during ev71 infection. althou ...201526419198
epidemiological characteristics and spatial-temporal clusters of hand, foot, and mouth disease in zhejiang province, china, 2008-2012.hand, foot and mouth disease (hfmd) is one of the major public health concerns in china. being the province with high incidence rates of hfmd, the epidemiological features and the spatial-temporal patterns of zhejiang province were still unknown. the objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. the surveillance data of hfmd during 2008-2012 were collected from the communicable disea ...201526422015
enterovirus-specific anti-peptide antibodies.enterovirus 71 (ev-71) is the main causative agent of hand, foot, and mouth disease (hfmd) which is generally regarded as a mild childhood disease. in recent years, ev71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in asia. a formalin-inactivated ev71 whole virus vaccine has completed phase iii trial in china but is currently unavailable clinically. the high cost of manufacturing and supply problems may limit p ...201526424285
a bivalent virus-like particle based vaccine induces a balanced antibody response against both enterovirus 71 and norovirus in mice.noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. genogroup ii.4 (gii.4) strains are responsible for the majority of norovirus outbreaks. enterovirus 71 (ev71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in asia-pacific regions, resulting in significant morbidity and mortality in young children. however, no vaccine is commercially availab ...201526424606
the suramin derivative nf449 interacts with the 5-fold vertex of the enterovirus a71 capsid to prevent virus attachment to psgl-1 and heparan sulfate.nf449, a sulfated compound derived from the antiparasitic drug suramin, was previously reported to inhibit infection by enterovirus a71 (ev-a71). in the current work, we found that nf449 inhibits virus attachment to target cells, and specifically blocks virus interaction with two identified receptors--the p-selectin ligand, psgl-1, and heparan sulfate glycosaminoglycan--with no effect on virus binding to a third receptor, the scavenger receptor scarb2. we also examined a number of commercially a ...201526430888
systematic review of economic evaluations of vaccination programs in mainland china: are they sufficient to inform decision making?the purpose of the study was to systematically review economic evaluations of vaccine programs conducted in mainland china. we searched for economic evaluations of vaccination in china published prior to august 3, 2015 in eight english-language and three chinese-language databases. each article was appraised against the 19-item consensus on health economic criteria list (chec-list). we found 23 papers evaluating vaccines against hepatitis b (8 articles), streptococcus pneumoniae (5 articles), hu ...201526435189
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