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Sample records for non-polio enterovirus diseases

  1. Non-Polio Enterovirus

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    ... Disease Viral Meningitis What is Polio? About Non-Polio Enteroviruses Recommend on Facebook Tweet Share Compartir Symptoms Lists symptoms of non-polio enterovirus infection… Transmission Explains how non-polio enteroviruses ...

  2. Environmental surveillance of non-polio enteroviruses in Iran

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    Kargar, Mohammad; Sadeghipour, Sara; Nategh, Rakhshandeh

    2009-01-01

    Background Enteroviruses can shed in feces for several weeks, so many excrete viruses can remain infectious for a long time in environment. Therefore, by detecting enteroviruses in environmental specimens and sewage, we can understand this virus circulation, the approximate ratio of contaminated persons in society and they are suitable indicators for environmental surveillance. Methods Since March 2006 to February 2007, 86 specimens from Sistan & Balouchestan,63 specimens from Tehran and 48 samples from Fars sewage disposal systems and surface water were collected by Grab Sample method and tested for enteroviruses directly by using two concentration methods: Pellet and Two-phase. Then Non-Polio Enteroviruses (NPEV) were serotyped by microneutralization method. Results Enteroviruses were isolated from 49(56.98%) of specimens in Sistan & Baluchestan,38(60.32%) in Tehran and 11(22.92%) in Fars. Besides, the majority of Non-Polio Enteroviruses related to Non-typable Enteroviruses (N.T.E.V), E11 (31.52%), COX-B (27.58%), E7 (17.73%) and E4 (21.67%). Conclusion Environmental surveillance has been used successfully in monitoring enteric virus circulation and assessing the extent or duration of epidemic non polioviruses in specific populations. The results of this research show the seasonal circulation of enteroviruses in different parts of Iran. PMID:19781063

  3. Environmental surveillance of non-polio enteroviruses in Iran

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    Sadeghipour Sara

    2009-09-01

    Full Text Available Abstract Background Enteroviruses can shed in feces for several weeks, so many excrete viruses can remain infectious for a long time in environment. Therefore, by detecting enteroviruses in environmental specimens and sewage, we can understand this virus circulation, the approximate ratio of contaminated persons in society and they are suitable indicators for environmental surveillance. Methods Since March 2006 to February 2007, 86 specimens from Sistan & Balouchestan,63 specimens from Tehran and 48 samples from Fars sewage disposal systems and surface water were collected by Grab Sample method and tested for enteroviruses directly by using two concentration methods: Pellet and Two-phase. Then Non-Polio Enteroviruses (NPEV were serotyped by microneutralization method. Results Enteroviruses were isolated from 49(56.98% of specimens in Sistan & Baluchestan,38(60.32% in Tehran and 11(22.92% in Fars. Besides, the majority of Non-Polio Enteroviruses related to Non-typable Enteroviruses (N.T.E.V, E11 (31.52%, COX-B (27.58%, E7 (17.73% and E4 (21.67%. Conclusion Environmental surveillance has been used successfully in monitoring enteric virus circulation and assessing the extent or duration of epidemic non polioviruses in specific populations. The results of this research show the seasonal circulation of enteroviruses in different parts of Iran.

  4. Non-polio enteroviruses associated with acute flaccid paralysis (AFP) and facial paralysis (FP) cases in Romania, 2001-2008.

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    Persu, Ana; Băicuş, Anda; Stavri, Simona; Combiescu, Mariana

    2009-01-01

    Acute flaccid paralysis is a complex clinical syndrome, with a wide variety of possible etiologies and with clinical manifestations that can vary according to age or geographical region. Enteroviruses (polioviruses and non-polio enteroviruses) are among the viral agents that can cause AFP. AFP surveillance is important for public health through its use in monitoring poliomyelitis, in the context of the Global Initiative to eradicate this disease. The current paper aims to assess the non-polio enteroviruses (NPEV) association with AFP and FP cases registered in Romania in the period 2001-2008 and to identify prevalent serotypes. Within the framework of Surveillance of AFP Cases Program, were collected samples from 579 children with AFP or FP (3.069 samples). The samples were processed and inoculated onto two types of cell culture (RD and L20B), according to WHO protocol. The identification of isolated viruses has been done by the reaction of seroneutralization with pools of specific antiserum and then with monospecific antiserum for confirmation. NPEV were isolated from 58 cases (123 positive samples). During the analyzed period, 23 NPEV serotypes have circulated (15 Echo serotypes and 8 coxsackie serotypes). The most frequently identified were the Echoviruses 13 and 11 and the coxsackie A viruses. 88% of positive cases have occurred in children between 1 and 5 years. As seasonal distribution, the peak of NPEV circulation was in the months August-September (36.2%). The paper provides information about NPEV circulation in Romania in the past 8 years, about its association with the AFP and FP and it indicates the need for monitoring NPEV circulation even after the eradication of poliomyelitis.

  5. Role of non-polio enterovirus infection in pediatric hemolytic uremic syndrome.

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    De Petris, Laura; Gianviti, Alessandra; Caione, Daniela; Innocenzi, Daniele; Edefonti, Alberto; Montini, Giovanni; De Palo, Tommaso; Tozzi, Alberto Eugenio; Caprioli, Alfredo; Rizzoni, Gianfranco

    2002-10-01

    Verocytotoxin-producing Escherichia coli(VTEC) infections cause most cases of hemolytic uremic syndrome (HUS); 10-30% of patients, however, are negative for VTEC infection. The etiology of HUS in VTEC-negative cases remains poorly understood. Before the association between VTEC infection and HUS was recognized, sporadic cases of HUS with enterovirus infection were reported in the literature. Since May 1988, most cases of HUS in Italy have been reported to the Italian surveillance system, and in 73% of these, evidence of VTEC infection was demonstrated. The aim of this study was to determine whether the frequency of enteroviral infections was different in the acute phase of VTEC-positive and VTEC-negative HUS. Eighty-nine patients were investigated for enteroviral infection, of whom 58 were VTEC positive and 31 VTEC negative. Two serum samples from each patient were examined for seroconversion to enterovirus (coxsackie, echovirus, and picornavirus) by a complement fixation test. Serological evidence of acute infection with non-polio enterovirus was found in 33 patients (37%) [20/58 (34.5%) VTEC positive and 13/31 (41.9%) VTEC negative]. There was no statistically significant difference between the two groups. These results demonstrate that there are no significant differences for enteroviral infection in VTEC-positive and VTEC-negative patients and, therefore, enteroviral infections should not be considered a cause of HUS in VTEC-negative children.

  6. Frequency of isolation of polioviruses and non polio enteroviruses from patients with acute flaccid paralysis, enterovirus infection and children from groups at risk

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    N. I. Romanenkova

    2012-01-01

    Full Text Available The article describes the frequency of isolation of polioviruses and non polio enteroviruses from different categories of the investigated children. The percentage of detection of polioviruses from the patients with acute flaccid paralysis was lower than that from the children from groups at risk. Among the patients with the enterovirus infection the polioviruses were rarely revealed. The frequency of isolation of non polio enteroviruses from these patients was significantly higher than that from the other categories of investigated persons. The improvement of poliomyelitis surveillance and the reinforcement of virological surveillance of children from groups at risk and those with enterovirus infection will provide the important data for Global Polio Eradication Initiative and the maintenance of polio free status of the Russian Federation.

  7. Detection of polioviruses and non-polio enteroviruses by acute flaccid paralysis and environmental surveillances in Sistan and Balouchestan Province

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    Saeideh alsadat Razavi

    2006-09-01

    Full Text Available Background: In some countries, though wild poliovirus isolation from clinical specimens has not been done, evidences of silent circulation of wild virus in sewage system have been reported. On the other hand, based on WHO recommendations, if there is any probability of wild virus entrance from endemic countries, environmental surveillance is advised as a completion to Acute Flaccid Paralysis (AFP surveillance. Methods: AFP and environmental surveillance were performed simultaneously in Sistan and Balouchestan province to confirm wild poliovirus eradication. To perform AFP surveillance, 21 stool specimens of AFP suspected cases were collected in a one year period and evaluated using L20B, RD and Hep-2 cell lines. To perform environmental surveillance, 86 samples from urban and hospital sewage disposal systems were collected. Using direct, Pellet and Two-phase methods for virus concentration, Enterovirus existence was investigated in above-mentioned cell lines. Results: Non-polio enteroviruses and polioviruses were isolated from 53.49% and 20.93% of sewage specimens, respectively. Sabin-Like polioviruses were isolated from 9.52% of AFP cases, and non-polio enteroviruses from 14.28% of them. Poliovirus type 2 was not isolated form stool specimens and there was no Poliovirus type 1 isolation from sewage specimens, either. Conclusion: The environmental surveillance as a completion to AFP in Sistan and Balouchestan Province in Iran confirms poliovirus eradication.

  8. An enzyme-linked immuno focus assay for rapid detection and enumeration, and a newborn mouse model for human non-polio enteroviruses associated with acute diarrhea.

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    Rao, C Durga; Reddy, Harikrishna; Naidu, Jagadish R; Raghavendra, A; Radhika, N S; Karande, Anjali

    2015-11-01

    We have recently reported significant association of non-polio enteroviruses (NPEVs) with acute and persistent diarrhea (18-21% of total diarrheal cases), and non-diarrheal Increased Frequency of Bowel Movements (IFoBM-ND) (about 29% of the NPEV infections) in children and that the NPEV-associated diarrhea was as significant as rotavirus diarrhea. However, their diarrhea-causing potential is yet to be demonstrated in an animal model system. Since the determination of virus titers by the traditional plaque assay takes 4-7 days, there is a need for development of a rapid method for virus titer determination to facilitate active clinical research on enterovirus-associated diarrhea. The goal of this study is to develop a cell-based rapid detection and enumeration method and to demonstrate the diarrhea-inducing potential of purified and characterized non-polio enteroviruses, which were isolated from diarrheic children. Here we describe generation of monoclonal and polyclonal antibodies against purified strains belonging to different serotypes, and development of an enzyme-linked immuno focus assay (ELIFA) for detection and enumeration of live NPEV particles in clinical and purified virus samples, and a newborn mouse model for NPEV diarrhea. Plaque-purified NPVEs, belonging to different serotypes, isolated from children with diarrhea, were grown in cell culture and purified by isopycnic CsCl density gradient centrifugation. By ELIFA, NPEVs could be detected and enumerated within 12h post-infection. Our results demonstrated that Coxsackievirus B1 (CVB1) and CVB5 strains, isolated from diarrheic children, induced severe diarrhea in orally-inoculated 9-12 day-old mouse pups, fulfilling Koch's postulates. The methods described here would facilitate studies on NPEV-associated gastrointestinal disease.

  9. Detection of non-polio enteroviruses from 17 years of virological surveillance of acute flaccid paralysis in the Philippines.

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    Apostol, Lea Necitas; Suzuki, Akira; Bautista, Analisa; Galang, Hazel; Paladin, Fem Julia; Fuji, Naoko; Lupisan, Socorro; Olveda, Remigio; Oshitani, Hitoshi

    2012-04-01

    Acute flaccid paralysis (AFP) surveillance has been conducted as part of the World Health Organization (WHO) strategy on poliomyelitis eradication. Aside from poliovirus, which is the target pathogen, isolation, and identification of non-polio enteroviruses (NPEVs) is also done by neutralization test using pools of antisera which can only identify limited number of NPEVs. In the Philippines, despite the significant number of isolated NPEVs, no information is available with regard to its occurrence, diversity, and pattern of circulation. In this study, a total of 790 NPEVs isolated from stool samples submitted to the National Reference Laboratory from 1992 to 2008 were analyzed; neutralization test was able to type 55% (442) of the isolates. Of the remaining 356 isolates, which were untyped by using neutralization test, 348 isolates were analyzed further by RT-PCR targeting the VP1 gene. A total of 47 serotypes of NPEV strains were identified using neutralization test and molecular typing, including 28 serotypes of human enterovirus B (HEV-B), 12 serotypes of HEV-A, and 7 of HEV-C. The HEV-B group (625/790; 79%) constituted the largest proportion of isolates, followed by HEV-C (108/790; 13.7%), HEV-A (57/790; 7.2%), and no HEV-D. Coxsackievirus (CV) B, echovirus (E)6, E11, and E13 were the most frequent isolates. E6, E11, E13, E14, E25, E30, E33, CVA20, and CVA24 were considered as endemic strains, some NPEVs recurred and few serotypes existed only for 1-3 years during the study period. Despite some limitations in this study, plural NPEVs with multiple patterns of circulation in the Philippines for 17 years were identified.

  10. Characterization of the non-polio enterovirus infections associated with acute flaccid paralysis in South-Western India.

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    Rongala Laxmivandana

    Full Text Available Non-polio enteroviruses (NPEVs have been reported frequently in association with acute flaccid paralysis (AFP cases during Polio Surveillance Programs (PSPs worldwide. However, there is limited understanding on the attributes of their infections. This study reports characteristics of NPEVs isolated from AFP cases, investigated during PSPs held in 2009-2010, in Karnataka and Kerala states of south-western India having varied climatic conditions. NPEV cell culture isolates derived from stool specimens that were collected from 422 of 2186 AFP cases (<1-14 years age and 17 of 41 asymptomatic contacts; and details of all AFP cases/contacts were obtained from National Polio Laboratory, Bangalore. The distribution of NPEV infections among AFP cases and circulation pattern of NPEV strains were determined by statistical analysis of the data. Genotyping of all NPEV isolates was carried out by partial VP1 gene sequencing and phylogenetic analysis. NPEV positive AFP cases were significantly higher in children aged <2 years; with residual paralysis; in summer months; and in regions with relatively hot climate. Genotyping of NPEVs identified predominance of human enteroviruses (HEV-B species [81.9%-Echoviruses (E: 57.3%; coxsackieviruses (CV B: 15%; numbered EVs: 8.9%; CVA9: 0.7%] and low levels of HEV-A [14.5%-CVA: 6%; numbered EVs: 8.5%] and HEV-C [3.6%-CVA: 2.6%; numbered EVs: 1%] species, encompassing 63 genotypes. EV76 (6.3% and each of E3, CVB3 and E9 (4.97% were found frequently during 2009 while E11 (6.7%, CVB1 (6.1%, E7 (5.1% and E20 (5.1% were detected commonly in 2010. A marked proportion of AFP cases from children aged <2 years; presenting with fever; and from north and south interior parts of Karnataka state was detected with E/numbered EVs than that found with CVA/CVB. This study highlights the extensive genetic diversity and diverse circulation patterns of NPEV strains in AFP cases from different populations and climatic conditions.

  11. Molecular surveillance of non-polio enterovirus infections in patients with acute gastroenteritis in Western India: 2004-2009.

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    Patil, Pooja R; Chitambar, Shobha D; Gopalkrishna, V

    2015-01-01

    Acute gastroenteritis is a major cause of childhood morbidity and mortality worldwide. Rotavirus (RV) and Norovirus (NoV) are the leading cause of the disease. Despite the use of improved diagnostic methods a significant proportion of gastroenteritis cases remained undiagnosed. Though nonpolio enteroviruses (NPEVs) have been reported frequently in children with acute gastroenteritis, their etiologic role has not been established. To investigate the epidemiology of NPEVs in gastroenteritis cases which remained negative for leading causative agents, 955 RV and NoV negative stool specimens from children hospitalized for acute gastroenteritis were included in the study. A case control study was conducted which includes stool specimens from 450 children with gastroenteritis and 162 asymptomatic control subjects to determine the association of NPEVs with the disease. NPEV detection and typing was carried out by RT-PCR and sequencing. Presence of RV, NoV, Adenovirus, and Astrovirus was confirmed by ELISA or PCR/RT-PCR. Overall 14% NPEV prevalence was noted. The percentage of children with NPEV infection differed significantly between gastroenteritis and non-gastroenteritis patients (13.7% vs. 4.9%). NPEV was more prevalent among patients with gastroenteritis of undetectable etiology as compared to those detected positive for other viruses (17.9% vs. 7%) (P gastroenteritis and highlights the clinical and epidemiological features of NPEV infections in patients with acute gastroenteritis from western India.

  12. Sporadic isolation of sabin-like polioviruses and high-level detection of non-polio enteroviruses during sewage surveillance in seven Italian cities, after several years of inactivated poliovirus vaccination.

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    Battistone, A; Buttinelli, G; Fiore, S; Amato, C; Bonomo, P; Patti, A M; Vulcano, A; Barbi, M; Binda, S; Pellegrinelli, L; Tanzi, M L; Affanni, P; Castiglia, P; Germinario, C; Mercurio, P; Cicala, A; Triassi, M; Pennino, F; Fiore, L

    2014-08-01

    Sewage surveillance in seven Italian cities between 2005 and 2008, after the introduction of inactivated poliovirus vaccination (IPV) in 2002, showed rare polioviruses, none that were wild-type or circulating vaccine-derived poliovirus (cVDPV), and many other enteroviruses among 1,392 samples analyzed. Two of five polioviruses (PV) detected were Sabin-like PV2 and three PV3, based on enzyme-linked immunosorbent assay (ELISA) and PCR results. Neurovirulence-related mutations were found in the 5'noncoding region (5'NCR) of all strains and, for a PV2, also in VP1 region 143 (Ile>Thr). Intertypic recombination in the 3D region was detected in a second PV2 (Sabin 2/Sabin 1) and a PV3 (Sabin 3/Sabin 2). The low mutation rate in VP1 for all PVs suggests limited interhuman virus passages, consistent with efficient polio immunization in Italy. Nonetheless, these findings highlight the risk of wild or Sabin poliovirus reintroduction from abroad. Non-polio enteroviruses (NPEVs) were detected, 448 of which were coxsackievirus B (CVB) and 294 of which were echoviruses (Echo). Fifty-six NPEVs failing serological typing were characterized by sequencing the VP1 region (nucleotides [nt] 2628 to 2976). A total of 448 CVB and 294 Echo strains were identified; among those strains, CVB2, CVB5, and Echo 11 predominated. Environmental CVB5 and CVB2 strains from this study showed high sequence identity with GenBank global strains. The high similarity between environmental NPEVs and clinical strains from the same areas of Italy and the same periods indicates that environmental strains reflect the viruses circulating in the population and highlights the potential risk of inefficient wastewater treatments. This study confirmed that sewage surveillance can be more sensitive than acute flaccid paralysis (AFP) surveillance in monitoring silent poliovirus circulation in the population as well as the suitability of molecular approaches to enterovirus typing.

  13. Epidemiología de los enterovirus asociados a enfermedades neurológicas Epidemiology of enterovirus associated with neurologic diseases

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    Daniel M. Cisterna

    2007-04-01

    . Echovirus 4 (E4, E9, E30 and E17 were identified from meningitis outbreaks. Coxsackievirus A2 (CAV2, CBV2, CBV5, E7, E11, E19, E24, E29 and enterovirus 71 were recovered only from sporadic cases. Three different serotypes were identified in encephalitis patients: E4, E7 and E24. A total of 28 different serotypes of non-polio enteroviruses were detected from acute flaccid paralysis cases. The information here presented contributes to improving our knowledge about enteroviruses epidemiology in Argentina and their relationship with different neurological diseases. This study provides valuable data that could be useful to further research.

  14. Human Enteroviruses isolated during acute flaccid paralysis surveillance in Ghana: implications for the post eradication era.

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    Odoom, John Kofi; Obodai, Evangeline; Barnor, Jacob Samson; Ashun, Miriam; Arthur-Quarm, Jacob; Osei-Kwasi, Mubarak

    2012-01-01

    Surveillance of acute flaccid surveillance (AFP) has been used world-wide to monitor the control and eradication of circulating wild polioviruses. The Polio Laboratory since its accreditation in 1996 has supported the Disease Surveillance Department for AFP surveillance. This study aims to isolate and characterize human enteroviruses from patients with AFP in Ghana. Stool suspension was prepared from 308 samples received in 2009 from the surveillance activities throughout the country and inoculated on both RD and L20B cell lines. Isolates that showed growth on L20B were selected for real-time RT-PCR using degenerate and non-degenerate primers and probes. RD isolates were however characterized by microneutralisation technique with antisera pools from RIVM, The Netherlands and viruses that were untypable subjected to neutralization assay using antibodies specific for E71. Of the 308 samples processed, 17 (5.5%) grew on both L20B and RD cells while 32 (10.4%) grew on RD only. All 28 isolates from L20B were characterized by rRT-PCR as Sabin-like polioviruses. No wild poliovirus or VDPV was found. However from the microneutralisation assay, six different enteroviruses were characterized. Among these, Coxsackie B viruses were most predominant followed by Echovirus. Three children from whom non-polio enteroviruses were isolated had residual paralysis while one child with VAPP found. The non-polio enteroviruses circulated throughout the country with the majority (20.7%) from Ashanti region. This study showed the absence of wild or vaccine-derived poliovirus circulation in the country. However, the detection of three non-polio enteroviruses and one Sabin-like poliovirus with residual paralysis call for continuous surveillance even in the post polio eradication era.

  15. Environmental Surveillance of Polio and Non-Polio Enterovi¬ruses in Sistan and Balouchestan Province

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    S Hamed Khodaei

    2008-09-01

    Full Text Available "nBackground: Enteroviruses can easily circulate in the population through sewage and they are suitable indicators for environ­mental surveillance. On the other hand, in some countries there are evidences of silent circulation of viruses in sew­age specimens despite no virus isolation from clinical specimens. Therefore, WHO has suggested environmental surveil­lance using surface water and sewage specimens for final confirmation of Poliovirus eradication. In this research, according to wild Poliovirus circulation in Afghanistan and Pakistan and probability of virus entrance to Iran, and also to assure wild Poliovi­rus eradication, the environmental surveillance was performed in Sistan and Balouchestan Province of Iran."nMethods: From March 2004 to February 2005, 86 specimens from 2 sewage disposal systems, 5 hospitals and surface water from several villages were collected by Grab Sample method and tested for Enteroviruses directly and using 2 concentration meth­ods: Pellet and Two-phase. Then Poliovirus and Non-Polio Enteroviruses (NPEV were serotyped by microneutraliza­tion method and Polioviruses were intratypically differentiated using ELISA and Probe Hybridization techniques."nResults: From a total of 86 specimens, Enteroviruses and Non-Polio Enteroviruses were isolated from 49(56.98% and 46(53.49% of specimens respectively. Polioviruses were isolated from 18(20.93% specimens and none of them was wild Poliovi­rus fortunately. 13(17.81%, 39(53.42% and 57(78.08% of enteroviruses were isolated using Direct, Pellet and Two-phase methods, respectively."nConclusions: The results of this research confirm the validity of environmental surveillance and Polio eradication in Sistan and Balouchestan Province. "n 

  16. Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity

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    Bessaud, Maël; Joffret, Marie-Line; Blondel, Bruno; Delpeyroux, Francis

    2016-01-01

    The attenuated Sabin strains contained in the oral poliomyelitis vaccine are genetically unstable, and their circulation in poorly immunized populations can lead to the emergence of pathogenic circulating vaccine-derived polioviruses (cVDPVs). The recombinant nature of most cVDPV genomes and the preferential presence of genomic sequences from certain cocirculating non-polio enteroviruses of species C (EV-Cs) raise questions about the permissiveness of genetic exchanges between EV-Cs and the phenotypic impact of such exchanges. We investigated whether functional constraints limited genetic exchanges between Sabin strains and other EV-Cs. We bypassed the natural recombination events by constructing 29 genomes containing a Sabin 2 capsid-encoding sequence and other sequences from Sabin 2 or from non-polio EV-Cs. Most genomes were functional. All recombinant viruses replicated similarly in vitro, but recombination modulated plaque size and temperature sensitivity. All viruses with a 5′UTR from Sabin 2 were attenuated in mice, whereas almost all viruses with a non-polio 5′UTR caused disease. These data highlight the striking conservation of functional compatibility between different genetic domains of cocirculating EV-Cs. This aspect is only one of the requirements for the generation of recombinant cVDPVs in natural conditions, but it may facilitate the generation of viable intertypic recombinants with diverse phenotypic features, including pathogenicity. PMID:27958320

  17. 非脊髓灰质炎肠道病毒感染对口服脊髓灰质炎减毒活疫苗免疫原性影响的Meta分析%Meta-Analysis of the Influence of Non-polio Enterovirus Infection on Immunogenicity of Oral Poliomyelitis Attenuated Live Vaccine

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    胡昱; 唐学雯; 郭静; 陈雅萍; 张兵

    2015-01-01

    目的 评价非脊髓灰质炎(脊灰)肠道病毒感染(Non-Poliomyelitis Enteroviruses Infection,nPEI)对口服脊灰减毒活疫苗(Oral Poliomyelitis Attenuated Live Vaccine,OPV)免疫原性的影响.方法 电子检索美国国家医学图书馆数据库(National Center for Biotechnology Information,NCBI)、考克兰(Cochrane)协作网图书馆等数据库,将有关nPEI对OPV免疫原性影响的研究纳入分析.使用综述管理(RevMan) 5.1软件进行统计分析.结果 共纳入13篇文献,nPEI对接种OPV后血清阳转率影响的相对危险度(Relative Risk,RR)是0.87 [95%可信区间(Confidence Interval,CI):0.79 ~0.97],其中nPEI对接种单价(Monovalent) OPV(mOPV)后阳转率影响的RR是0.69(95% CI:0.63~0.76),对接种三价(Trivalent) OPV(tOPV)后阳转率影响的RR是0.96(95% CI:0.84~1.09);nPEI对肠道疫苗病毒排出率(Vaccine Virus Shedding Rate,VVSR)影响的RR是0.78(95% CI:0.61~1.00),其中nPEI对接种mOPV后VVSR影响的RR是0.54(95% CI:0.45 ~0.64),对接种tOPV后VVSR影响的RR是1.11(95% CI:0.83~1.46).结论 nPEI可降低OPV血清型Ⅰ免疫原性的同时,也可降低mOPV的免疫原性.提示制定OPV免疫策略时,应考虑nPEI的因素,如尽量避开nPEI高发季节.

  18. Neurotropic Enterovirus Infections in the Central Nervous System

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    Hsing-I Huang

    2015-11-01

    Full Text Available Enteroviruses are a group of positive-sense single stranded viruses that belong to the Picornaviridae family. Most enteroviruses infect humans from the gastrointestinal tract and cause mild symptoms. However, several enteroviruses can invade the central nervous system (CNS and result in various neurological symptoms that are correlated to mortality associated with enteroviral infections. In recent years, large outbreaks of enteroviruses occurred worldwide. Therefore, these neurotropic enteroviruses have been deemed as re-emerging pathogens. Although these viruses are becoming large threats to public health, our understanding of these viruses, especially for non-polio enteroviruses, is limited. In this article, we review recent advances in the trafficking of these pathogens from the peripheral to the central nervous system, compare their cell tropism, and discuss the effects of viral infections in their host neuronal cells.

  19. Enteroviruses isolated from herpangina and hand-foot-and-mouth disease in Korean children

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    Park KwiSung

    2012-09-01

    Full Text Available Abstract Hand-foot-and-mouth disease (HFMD and herpangina are commonly prevalent illness in young children. They are similarly characterized by lesions on the skin and oral mucosa. Both diseases are associated with various enterovirus serotypes. In this study, enteroviruses from patients with these diseases in Korea in 2009 were isolated and analyzed. Demographic data for patients with HFMD and herpangina were compared and all enterovirus isolates were amplified in the VP1 region by reverse transcription-polymerase chain reaction and sequenced. Among the enterovirus isolates, prevalent agents were coxsackievirus A16 in HFMD and coxsackievirus A5 in herpangina. More prevalent months for HFMD were June (69.2% and May (11.5%, and June (40.0% and July (24.0% for herpangina. Age prevalence of HFMD patients with enterovirus infection was 1 year (23.1%, 4 years (19.2%, and over 5 years (19.2%. However, the dominant age group of herpangina patients with enterovirus infection was 1 year (48.0% followed by 2 years (28.0%. Comparison of pairwise VP1 nucleotide sequence alignment of all isolates within the same serotypes revealed high intra-type variation of CVA2 isolates (84.6–99.3% nucleotide identity. HFMD and herpangina showed differences in demographic data and serotypes of isolated enteroviruses, but there was no notable difference in amino acid sequences by clinical syndromes in multiple comparison of the partial VP1 gene sequence.

  20. Characteristics of pediatric patients with enterovirus meningitis and no cerebral fluid pleocytosis

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    de Crom, Stephanie C. M.; van Furth, Marceline A. M.; Peeters, Marcel F.; Rossen, John W. A.; Obihara, Charles C.

    2012-01-01

    UNLABELLED: Human non-polio enterovirus (EV) is the most important cause of aseptic meningitis in children. Only a few studies report the lack of cerobrospinal fluid (CSF) pleocytosis in children with confirmed EV meningitis; however, the characteristics of these children have not been well defined.

  1. Epidemiological survey enterovirus infection in of neonatal non-polio the Netherlands

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    Verboon-Maciolek, MA; Krediet, TG; van Loon, AM; Kaan, J; Galama, JMD; Gerards, LJ; Fleer, A

    2002-01-01

    The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1

  2. Epidemiological survey of neonatal non-polio enterovirus infection in the Netherlands.

    NARCIS (Netherlands)

    Verboom-Maciolek, M.A.; Krediet, T.G.; Loon, A.M. van; Kaan, J.A.; Galama, J.M.D.; Gerards, L.J.; Fleer, A.

    2002-01-01

    The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1

  3. Characterization of a novel enterovirus serotype and an enterovirus EV-B93 isolated from acute flaccid paralysis patients.

    Directory of Open Access Journals (Sweden)

    Shahzad Shaukat

    Full Text Available Non-polio enteroviruses (NPEVs are among the most common viruses infecting humans worldwide. Most of these infections are asymptomatic but few can lead to systemic and neurological disorders like Acute Flaccid Paralysis (AFP. Acute Flaccid Paralysis is a clinical syndrome and NPEVs have been isolated frequently from the patients suffering from AFP but little is known about their causal relationship. The objective of this study was to identify and characterize the NPEV serotypes recovered from 184 stool samples collected from AFP patients in Federally Administered Tribal Areas (FATA in north-west of Pakistan. Overall, 44 (95.6 % isolates were successfully typed through microneutralization assay as a member of enterovirus B species including echovirus (E-2, E-3, E-4, E-6, E-7, E-11, E-13, E-14, E-21 and E-29 while two isolates (PAK NIH SP6545B and PAK NIH SP1202B remained untypeable. The VP1 and capsid regions analysis characterized these viruses as EV-B93 and EV-B106. Phylogenetic analysis confirmed that PAK NIH isolates had high genetic diversity and represent distinct genotypes circulating in the country. Our findings highlight the role of NPEVs in AFP cases to be thoroughly investigated especially in high disease risk areas, with limited surveillance activities and health resources.

  4. Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark

    DEFF Research Database (Denmark)

    Sørup, Signe; Stensballe, Lone G; Krause, Tyra Grove;

    2015-01-01

    Background.  Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children with inactiv......Background.  Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children...... with inactivated diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) or live measles-mumps-rubella vaccine (MMR) as their most recent vaccine. Methods.  A nationwide, register-based, retrospective cohort study of 137 403 Danish children born 1997-1999, who had received 3 doses...... of DTaP-IPV-Hib, were observed from 24 months (first OPV dose) to 36 months of age. Results.  Oral polio vaccine was associated with a lower rate of admissions with any type of non-polio infection compared with DTaP-IPV-Hib as most recent vaccine (adjusted incidence rate ratio [IRR], 0.85; 95% confidence...

  5. Prevalence of human enteroviruses among apparently healthy nursery school children in Accra.

    Science.gov (United States)

    Attoh, Juliana; Obodai, Evangeline; Adiku, Theophilus; Odoom, John Kofi

    2014-01-01

    Human enteroviruses are common in children causing asymptomatic infections ranging from mild to severe illnesses. In Ghana, information on the prevalence of non-polio enterovirus causing acute flaccid paralysis is available but data on surveillance of these viruses in school children is scanty. Here, the prevalence of human enteroviruses among apparently healthy children in selected school in Accra was studied. Stool samples from 273 apparently healthy children less than eight years of age in 9 selected nursery schools were collected between December 2010 and March 2011 and processed for human enteroviruses on L20B, RD and Hep-2 cell lines. Positive Isolates were characterized by microneutralisation assay with antisera pools from RIVM, the Netherlands according to standard methods recommended by WHO. Of the 273 samples processed, 66 (24.2%) non-polio enteroviruses were isolated. More growth was seen on Hep-2C (46%) only than RD (18%) only and on both cell lines (34%). No growth was seen on L20B even after blind passage. Excretion of non-polio enteroviruses was found in all the schools with majority in BD school. Serotyping of the isolates yielded predominantly Coxsackie B viruses followed by echoviruses 13 and 7. More than half of the isolates could not be typed by the antisera pools. The study detected 13 different serotypes of non-polio enteroviruses in circulation but no poliovirus was found. BD school was found to have the highest prevalence of NPEV. Complete identification through molecular methods is essential to establish the full range of NPEVs in circulation in these schools.

  6. Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children

    NARCIS (Netherlands)

    de Crom, S. C. M.; Rossen, J. W. A.; de Moor, R. A.; Veldkamp, E. J. M.; van Furth, A. M.; Obihara, C. C.

    2016-01-01

    Background: Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. Obje

  7. Coxsackievirus A6 and enterovirus 71 causing hand, foot and mouth disease in Cuba, 2011-2013.

    Science.gov (United States)

    Fonseca, Magilé C; Sarmiento, Luis; Resik, Sonia; Martínez, Yenisleidys; Hung, Lai Heng; Morier, Luis; Piñón, Alexander; Valdéz, Odalys; Kourí, Vivian; González, Guelsys

    2014-09-01

    Hand, foot and mouth disease (HFMD) is usually caused by coxsackievirus A16 or enterovirus 71 (EV71). Between 2011 and 2013, HFMD cases were reported from different Cuban provinces. A total of 42 clinical specimens were obtained from 23 patients. Detection, identification and phylogenetic analysis of enterovirus-associated HFMD were carried out by virus isolation, specific enterovirus PCR and partial VP1 sequences. HEV was detected in 11 HFMD cases. Emerging genetic variants of coxsackievirus A6 and EV71 were identified as the causative agents of the Cuban HFMD cases.

  8. Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71.

    Science.gov (United States)

    Zhang, Yu-Feng; Deng, Hui-Ling; Fu, Jia; Zhang, Yu; Wei, Jian-Qiang

    2016-02-14

    Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis.

  9. Neutralizing Antibodies to Enterovirus 71 in Belém, Brazil

    Directory of Open Access Journals (Sweden)

    Gomes Maria de Lourdes C

    2002-01-01

    Full Text Available Non-polio enteroviruses (Coxsackievirus A, Coxsackievirus B, Echovirus and EV 68-72 which belong to the enterovirus (EV genus, Picornaviridae family, may be responsible for acute flaccid paralysis, aseptic meningitis, myocarditis, hepatitis, pleurodinia, neonatal sepsis, hand, foot and mouth disease (HFMD even though 50-80% of infections are asymptomatic. EV 71 has been responsible for outbreaks and epidemics of HFMD and acute neurologic disease justifying its study in our country. The aim of this study was to detect neutralizing antibodies (NtAb to EV 71 in individuals up to 15 years of age living in Belém, State of Pará, northern Brazil. Serum samples from 238 patients attending the Virology Sector of Evandro Chagas Institute in Belém, Brazil, were analyzed using microneutralization tests that included RD cells and BrCr strain. Overall 40.8% (97/238 of tested samples had NtAb to EV 71. Regarding the distribution per age group, 85.2% (92/108 of patients aged 0-3 years had no NtAb to this virus and 69.2% of those 12 to15 years of age were seropositive. These results confirm that EV 71 infection occurs in the city of Belém; and that a high rate of individuals in this study were infected aged 3 years and over and, when aged 15 years nearly 70% had EV 71 NtAb.

  10. Survey of enterovirus infections from hand, foot and mouth disease outbreak in china, 2009

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    Yang Fan

    2011-11-01

    Full Text Available Abstract Background In China, a rapid expansion of Hand, foot, and mouth disease (HFMD outbreaks has occurred since 2004 and HFMD has become an important issue for China. However, people are still only concerned with human enterovirus 71(HEV-71 and coxsackie virus A16 (CV-A16. Much of what is known about the other enterovirus infections relies on fractional evidence and old epidemic data, with little knowledge concerning their distribution. To alert potential threatens of the other enteroviruses, our study genetically characterized specimens from different regions of China and yielded novel information concerning the circulating and phylogenetic characteristics of enteroviral strains from HFMD cases. Findings A total of 301 clinical throat swabs were randomly obtained from patients suffering from HFMD from the southern, northern and central regions of China during outbreaks in 2009. 266 of 301 (88.4% HFMD cases were found positive for HEV and seven genotypes, HEV-71, CV-A16, -B5, -A4, -A6, -A10, and -A12, were detected. Conclusions The HFMD pathogen compositions in the different regions of China were significantly different. HFMD epidemics might persist for a long time in China due to the multiple pathogen compositions, the enteroviral characteristic of recombination and co-infection, the ever-increasing travel and migration and the deficiency of effective vaccine. Our study deserves the attention on HFMD control and vaccine development.

  11. Distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications

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    Xu Wei

    2012-01-01

    Full Text Available Abstract Background To explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (HFMD complicated with nervous system disease. 234 hospitalized HFMD patients treated in Shengjing Hospital, Liaoning Province were analyzed retrospectively. Based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. Based on the detected pathogen, the patients were grouped as follows: Enterovirus 71 (EV71 infection, coxsackie A16 (CA16 infection and other enterovirus (OE infection. Results Of the 423 hospitalized patients, most were admitted in July 2010(129/423, 30.5%. Enteroviruses were detected in 177(41.8%. 272/423 patients were male (64.3%, and fatal patients had the greatest proportion of male patients (p p p p p p Conclusion The disease progresses faster in EV71-infected HFMD patients. These patients are more likely to suffer nervous system damage, neurogenic pulmonary edema, severe sequelae or death. CA16 and other enteroviruses can also cause HFMD with severe nervous system complications.

  12. Plaque morphology of Teschen disease viruses and certain pig enteroviruses in primary pig kidney monolayer cultures.

    Science.gov (United States)

    Dardiri, A H

    1968-04-01

    Plaque patterns and diameters of four virulent strains and one tissue culture mutant of Teschen disease virus were compared with six pig enteroviruses isolated in the United States. They are described as they were produced in primary pig kidney monolayer cultures. Reproducible plaques, with similar characteristics and class-types of each of the viruses tested were obtained with the application of a 45-minute virus adsorption time. Their morphologic characteristics and the proportion in which the plaque types appeared may assist in the differentiation of these virus strains.

  13. Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia.

    OpenAIRE

    Nmn NikNadia; I-Ching Sam; Sanjay Rampal; Wmz WanNorAmalina; Ghazali NurAtifah; Khebir Verasahib; Chia Ching Ong; MohdAidinniza MohdAdib; Yoke Fun Chan

    2016-01-01

    Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2–3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples c...

  14. Prevalence and characterization of enterovirus infections among pediatric patients with hand foot mouth disease, herpangina and influenza like illness in Thailand, 2012.

    Science.gov (United States)

    Puenpa, Jiratchaya; Mauleekoonphairoj, John; Linsuwanon, Piyada; Suwannakarn, Kamol; Chieochansin, Thaweesak; Korkong, Sumeth; Theamboonlers, Apiradee; Poovorawan, Yong

    2014-01-01

    Hand, foot, and mouth disease (HFMD) and herpangina are common infectious diseases caused by several genotypes of human enterovirus species A and frequently occurring in young children. This study was aimed at analyzing enteroviruses from patients with these diseases in Thailand in 2012. Detection and genotype determination of enteroviruses were accomplished by reverse transcription-polymerase chain reaction and sequencing of the VP1 region. Enterovirus-positive samples were differentiated into 17 genotypes (coxsackievirus A4 (CAV4), A5, A6, A8, A9, A10, A12, A16, A21, B1, B2, B4, B5, echovirus 7, 16, 25 and Enterovirus 71). The result showed CAV6 (33.5%), followed by CAV16 (9.4%) and EV71 (8.8%) as the most frequent genotypes in HFMD, CAV8 (19.3%) in herpangina and CAV6 (1.5%) in influenza like illness. Enterovirus infections were most prevalent during July with 34.4% in HFMD, 39.8% in herpangina and 1.6% in ILI. The higher enterovirus infection associated with HFMD and herpangina occurred in infants over one year-old. This represents the first report describing the circulation of multiple enteroviruses in Thailand.

  15. Human enteroviruses are not the cause of neurological impairments in children at the Korle-Bu Teaching Hospital.

    Science.gov (United States)

    Tettey, Prudence; Badoe, Ebenezer; Adiku, Theophilus; Obodai, Eva; Odoom, John Kofi

    2014-01-01

    Convulsions associated with fever and acute onset of unknown aetiology with case fatalities have become a long observed medical condition at the Child Health Department of the Korle-Bu Teaching Hospital. Children admitted to the department with seizures of undetermined origin and fever has been a source of diagnostic confusion. Studies from the Asia Pacific region suggest a link with non-polio enteroviruses. The aim of the study was to investigate the association between non-polio enterovirus and acute encephalopathy causing neurological morbidity in children. One hundred and fifty cerebrospinal fluid (CSF), throat swab and serum samples were collected from participants at the Child Health Department of the Korle-Bu Teaching Hospital for virus isolation and characterization. Samples were cultured on cells and positive culture assayed by microneutralisation. Direct PCR as well as multiplex PCR were used to detect other viral agents present. Enterovirus isolation rate was approximately 0.67%. Intratypic differentiation by molecular characterization identified a poliovirus from vaccine origin. Further screening by real-time RT-PCR identified the virus as normal Sabin and not vaccine-derive poliovirus. No arbovirus was however detected. Non-polio enteroviruses and chikugunya virus were found not to be the etiologic agent responsible for the convulsion with neurologic morbidity observed in the Ghanaian children. Investigation for other viral agents is recommended.

  16. Hand foot and mouth disease due to enterovirus 71 in Malaysia.

    Science.gov (United States)

    Chua, Kaw Bing; Kasri, Abdul Rasid

    2011-08-01

    Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth. The illness is caused by a number of enteroviruses with coxsackievirus A16 and enterovirus 71 as the main causative agents. Human enterovirus 71 (EV71) belongs to the species Human enterovirus A under the genus Enterovirus within the family Picornaviridae. EV71 has been associated with an array of clinical diseases including hand foot and mouth disease (HFMD), aseptic meningitis, encephalitis and poliomyelitis-like acute flaccid paralysis. A large outbreak of HFMD due to highly neurovirulent EV71 emerged in Malaysia in 1997, and caused 41 deaths amongst young children. In late 2000, a recurrence of an outbreak of HFMD occurred in Malaysia with 8 fatalities in peninsular Malaysia. Outbreak of HFMD due to EV71 recurred in 2003 with an unknown number of cases and mortalities. A similar outbreak of HFMD with 2 recorded deaths in young children occurred in peninsular Malaysia in late 2005 and this was followed by a larger outbreak in Sarawak (Malaysian Borneo) with 6 reported fatalities in the early part of 2006. The current on-going outbreak of HFMD started in peninsular Malaysia in epidemiological week 12 of 2010. As with other HFMD outbreaks in Malaysia, both EV71 and CA16 were the main aetiological viruses isolated. In similarity with the HFMD outbreak in 2005, the isolation of CA16 preceded the appearance of EV71. Based on the VP1 gene nucleotide sequences, 4 sub-genogroups of EV71 (C1, C2, B3 and B4) co-circulated and caused the outbreak of hand, foot and mouth disease in peninsular Malaysia in 1997. Two sub-genogroups (C1 and B4) were noted to cause the outbreak in 2000 in both peninsular Malaysia and Sarawak. EV71 of sub-genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak in 2003. In the 2005 outbreak

  17. Hand Foot and Mouth Disease Due to Enterovirus 71 in Malaysia

    Institute of Scientific and Technical Information of China (English)

    Kaw Bing Chua; Abdul Rasid Kasri

    2011-01-01

    Hand foot and mouth disease is a febrile sickness complex characterized by cutaneous eruption (exanthem) on the palms and soles with simultaneous occurrence of muco-cutanous vesiculo-ulcerative lesions (enanthem) affecting the mouth.The illness is caused by a number of enteroviruses with coxsackievirus A16 and enterovirus 71 as the main causative agents.Human enterovirus 71 (EV71) belongs to the species Human enterovirus A under the genus Enterovirus within the family Picornaviridae.EV71 has been associated with an array of clinical diseases including hand foot and mouth disease (HFMD),aseptic meningitis,encephalitis and poliomyelitis-like acute flaccid paralysis.A large outbreak of HFMD due to highly neurovirulent EV71 emerged in Malaysia in 1997,and caused 41deaths amongst young children.In late 2000,a recurrence of an outbreak of HFMD occurred in Malaysia with S fatalities in peninsular Malaysia.Outbreak of HFMD due to EV71 recurred in 2003 with an unknown number of cases and mortalities.A similar outbreak of HFMD with 2 recorded deaths in young children occurred in peninsular Malaysia in late 2005 and this was followed by a larger outbreak in Sarawak (Malaysian Borneo) with 6 reported fatalities in the early part of 2006.The current on-going outbreak of HFMD started in peninsular Malaysia in epidemiological week 12 of 2010.As with other HFMD outbreaks in Malaysia,both EV71 and CA16 were the main aetiological viruses isolated.In similarity with the HFMD outbreak in 2005,the isolation of CA16 preceded the appearance of EV71.Based on the VP 1 gene nucleotide sequences,4 sub-genogroups of EV71 (C1,C2,B3 and B4) co-circulated and caused the outbreak of hand,foot and mouth disease in peninsular Malaysia in 1997.Two sub-genogroups (C1 and B4) were noted to cause the outbreak in 2000 in both peninsular Malaysia and Sarawak.EV71 of sub-genogroup B5 with smaller contribution from sub-genogroup C1 caused the outbreak in 2003.In the 2005 outbreak,besides the EV71 strains

  18. The Autophagic Machinery in Enterovirus Infection

    Directory of Open Access Journals (Sweden)

    Jeffrey K. F. Lai

    2016-01-01

    Full Text Available The Enterovirus genus of the Picornaviridae family comprises many important human pathogens, including polioviruses, rhinovirus, enterovirus A71, and enterovirus D68. They cause a wide variety of diseases, ranging from mild to severe life-threatening diseases. Currently, no effective vaccine is available against enteroviruses except for poliovirus. Enteroviruses subvert the autophagic machinery to benefit their assembly, maturation, and exit from host. Some enteroviruses spread between cells via a process described as autophagosome-mediated exit without lysis (AWOL. The early and late phases of autophagy are regulated through various lipids and their metabolizing enzymes. Some of these lipids and enzymes are specifically regulated by enteroviruses. In the present review, we summarize the current understanding of the regulation of autophagic machinery by enteroviruses, and provide updates on recent developments in this field.

  19. Alteration of serum high-mobility group protein 1 (HMGB1) levels in children with enterovirus 71-induced hand, foot, and mouth disease

    OpenAIRE

    Zheng, Weikun; Shi, Haifan; Chen, Yiping; Xu, Zhiwei; Chen, Jie; Jin, Longteng

    2017-01-01

    Abstract Hand, foot, and mouth disease (HFMD) is a common pediatric disease caused by enterovirus infection. It typically presents as a fever along with flat, discolored spots and bumps on the hands, feet, and mouth. Compared with other viruses, enterovirus 71 (EV71)-induced HFMD is more prone to cause severe complications in children, such as brainstem encephalitis, cardiopulmonary disorders, and even death. More in-depth studies are still necessary to understand the characteristics of EV71-...

  20. Epidemiology of enterovirus types causing neurological disease in Austria 1999-2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes.

    Science.gov (United States)

    Ortner, Birgit; Huang, Chiao-Wei; Schmid, Daniela; Mutz, Ingomar; Wewalka, Günther; Allerberger, Franz; Yang, Jyh-Yuan; Huemer, Hartwig P

    2009-02-01

    Between 1999 and 2007 1,388 stool specimens from patients with acute flaccid paralysis or aseptic meningitis were submitted to the Austrian reference laboratory for poliomyelitis. Samples (201) yielded non-poliovirus enterovirus in culture. One hundred eighty-one viruses were available for typing and 78 isolates which remained serologically untyped were further analyzed by CODEHOP-PCR and sequencing of the VP1 gene and the 5'-untranslated region (5'-UTR). Typing revealed an Echovirus 30 outbreak in northwestern Austria in 2000, which was in accordance with the situation in Europe, and no dramatic seasonal changes of Coxsackie viruses were observed. In 2002/2003 a small outbreak of enterovirus 71 (EV71), affected 12 patients in the province of Styria. This virus was identified as genotype C1 and appeared to be genetically distinct from the isolates observed in 2001/2002 in Vienna. In 2004 two unrelated cases occurred in Lower Austria, which were identified as genotype C4, which has been described associated with high mortality most recently in China. In contrast to the situation in Asia the detected EV71 cases were not associated with hand-foot-mouth disease, but with serous meningitis only. This was surprising as a recent publication suggested a reduced neurovirulence of C1 genotype in children in Norway, presumably due to alterations in 5'-UTR and polymerase gene. However, comparing the 5'-UTR of the Austrian isolates and established virulent reference strains to the Norwegian isolate and an attenuated EV71 laboratory strain we did not find an indication that the genotype C1 possesses a RNA structure in its 5'-UTR leading to reduced neurovirulence.

  1. Etiology of Multiple Non-EV71 and Non-CVA16 Enteroviruses Associated with Hand, Foot and Mouth Disease in Jinan, China, 2009-June 2013.

    Directory of Open Access Journals (Sweden)

    Hengyun Guan

    Full Text Available Hand, foot, and mouth disease (HFMD is an infectious disease caused by human enterovirus 71 (EV71, coxsackievirus A16 (CVA16 and other enteroviruses. It is of interest that other enteroviruses associated with HFMD in Jinan have been rarely reported. The aim of the present study is to detect and characterize the circulating serotypes of non-EV71 and non-CVA16 enteroviruses associated with HFMD in Jinan city, Shandong province, China. A total of 400 specimens were collected from clinically diagnosed HFMD cases in Jinan from January 2009 to June 2013. All specimens were infected with non-EV71 and non-CVA16 enteroviruses previously confirmed by RT-PCR or real-time PCR according to the protocols at that time. The GeXP-based multiplex RT-PCR assay (GeXP assay was performed to investigate the pathogen spectrum of 15 enteroviruses (coxsackieviruses A4, A5, A6, A9, A10, A16; coxsackieviruses B1, B3, B5; Echoviruses 6, 7, 11, 13, 19 and EV71 infections associated with HMFD. For GeXP assay negative samples, reverse transcription nested PCR (nested RT-PCR based on the 5' -untranslated region (5'- UTR sequence and phylogenetic analysis were conducted to further explore the etiology of multiple enteroviruses. The results showed that a total of twenty serotypes of enteroviruses (including EV71 and CVA16 were identified by GeXP assay and nested RT-PCR. The most circulating twelve serotypes of enteroviruses with HFMD in Jinan from 2009 to June 2013 were EV71, CVA16, CVA10, CVA6, CVA12, CVA2, Echo3, CVA4, CVA9, CVB1, CVB3 and Echo6. CVA10 and CVA6 were the most prevalent pathogens other than EV71 and CVA16 in Jinan and their most prevalent seasons were spring and summer, and a slight increase was observed in autumn and early winter. It should be noted that mixed-infections were identified by GeXP assay and the phylogenetic tree clearly discriminated the multiple pathogens associated with HFMD. Our results thus demonstrate that there was a clear lack of a reliable

  2. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

    Science.gov (United States)

    Han, Jun; Wang, Ying; Gan, Xing; Song, Juan; Sun, Peng; Dong, Xiao-Ping

    2014-08-01

    Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1β, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients.

  3. Excretion of enterovirus 71 in persons infected with hand, foot and mouth disease

    Directory of Open Access Journals (Sweden)

    Li Jie

    2013-01-01

    Full Text Available Abstract Background Hand, foot and mouth disease (HFMD is a common illness in young children. It also can be seen in adults occasionally. Enterovirus 71 (EV71, a pathogen that causes not only HFMD but also neurological complications and even death, has caused many HFMD outbreaks in China. However, till now the data about the duration of EV71 shedding is very limited. Results A total of 136 throat swabs and fecal samples were collected from 27 children and 3 adults, which includs 7 close contacts, 9 mild cases and 14 severe cases,. The participants were divided into three groups namely, severe case group, mild case group and close contact group. All the samples were assayed with real-time polymerase chain reaction (PCR. Kruskal-Wallis Test was employed to compare the difference in duration of viral RNA shedding among three groups. The results showed that significant difference in duration of EV71 shedding was found among three groups (P  Conclusions HFMD is characterized by extended excretion of EV71. Our results suggest that the duration of EV71 shedding is correlated with the severity of the disease. EV71 shedding through feces can persist more than 54 days. Prolonged virus shedding is a potential risk factor of proliferating HFMD epidemic.

  4. Adaptation of enterovirus 71 to adult interferon deficient mice.

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    Elizabeth A Caine

    Full Text Available Non-polio enteroviruses, including enterovirus 71 (EV71, have caused severe and fatal cases of hand, foot and mouth disease (HFMD in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN receptor deficient and AG129 (α/β, γ IFN receptor deficient mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p. into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m. in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05. The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection

  5. Antiviral activity of Paulownia tomentosa against enterovirus 71 of hand, foot, and mouth disease.

    Science.gov (United States)

    Ji, Ping; Chen, Changmai; Hu, Yanan; Zhan, Zixuan; Pan, Wei; Li, Rongrong; Li, Erguang; Ge, Hui-Ming; Yang, Guang

    2015-01-01

    The bark, leaves, and flowers of Paulownia trees have been used in traditional Chinese medicine to treat infectious and inflammatory diseases. We investigated the antiviral effects of Paulownia tomentosa flowers, an herbal medicine used in some provinces of P. R. China for the treatment of skin rashes and blisters. Dried flowers of P. tomentosa were extracted with methanol and tested for antiviral activity against enterovirus 71 (EV71) and coxsackievirus A16 (CAV16), the predominant etiologic agents of hand, foot, and mouth disease in P. R. China. The extract inhibited EV71 infection, although no effect was detected against CAV16 infection. Bioactivity-guided fractionation was performed to identify apigenin as an active component of the flowers. The EC50 value for apigenin to block EV71 infection was 11.0 µM, with a selectivity index of approximately 9.3. Although it is a common dietary flavonoid, only apigenin, and not similar compounds like naringenin and quercetin, were active against EV71 infection. As an RNA virus, the genome of EV71 has an internal ribosome entry site that interacts with heterogeneous nuclear ribonucleoproteins (hnRNPs) and regulates viral translation. Cross-linking followed by immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that EV71 RNA was associated with hnRNPs A1 and A2. Apigenin treatment disrupted this association, indicating that apigenin suppressed EV71 replication through a novel mechanism by targeting the trans-acting factors. This study therefore validates the effects of Paulownia against EV71 infection. It also yielded mechanistic insights on apigenin as an active compound for the antiviral activity of P. tomentosa against EV71 infection.

  6. Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia.

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    Nmn NikNadia

    2016-03-01

    Full Text Available Enterovirus A71 (EV-A71 is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2-3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence. Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance. A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24-1.69; P<0.001. Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01-1.34 P<0.034. In summary, the 2-3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs.

  7. Receptors for enterovirus 71

    OpenAIRE

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2014-01-01

    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 crit...

  8. Complete genome sequence analysis of enterovirus 71 isolated from children with hand, foot, and mouth disease in Thailand, 2012-2014.

    Science.gov (United States)

    Mauleekoonphairoj, John; Vongpunsawad, Sompong; Puenpa, Jiratchaya; Korkong, Sumeth; Poovorawan, Yong

    2015-10-01

    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 data from this work will contribute to the study of evolution dynamics of EV71.

  9. Change of Major Genotype of Enterovirus 71 in Outbreaks of Hand-Foot-and-Mouth Disease in Taiwan between 1998 and 2000

    OpenAIRE

    Wang, Jen-Ren; Tuan, Yen-Chang; Tsai, Huey-Pin; Yan, Jing-Jou; Liu, Ching-Chuan; Su, Ih-Jen

    2002-01-01

    Two outbreaks of hand-foot-and-mouth disease (HFMD) occurred in Taiwan between 1998 and 2000. Enteroviruses were isolated from a total of 1,892 patients in this laboratory during this period. Of the virus isolates, enterovirus 71 (EV71) was diagnosed in 44.4% of the patients (132 of 297) in 1998, 2% (13 of 646) in 1999, and 20.5% (195 of 949) in 2000. Genetic analyses of the 5′-untranslated and VP1 regions of EV71 isolates by reverse transcription-PCR and sequencing were performed to understa...

  10. Recombinant adeno-vaccine expressing enterovirus 71-like particles against hand, foot, and mouth disease.

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    Yueh-Liang Tsou

    2015-04-01

    Full Text Available Enterovirus 71 (EV71 and coxsackieviruses (CV are the major causative agents of hand, foot and mouth disease (HFMD. There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71 vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-γ T cells associated with Th1/Th2-balanced IFN-ɣ, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-γ T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and

  11. Recombinant Human Enterovirus 71

    OpenAIRE

    2004-01-01

    Two human enterovirus 71 (HEV71) isolates were identified from hand, foot and mouth disease patients with genome sequences that had high similarity to HEV71 (>93%) at 5´ UTR, P1, and P2 and coxsackievirus A16 (CV-A16, >85%) at P3 and 3´UTR. Intertypic recombination is likely to have occurred between HEV71 and CV-A16 or an as-yet to be described CV-A16-like virus.

  12. Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination.

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    Saki Takahashi

    2016-02-01

    Full Text Available Hand, foot, and mouth disease (HFMD is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71 and Coxsackievirus A16 (CV-A16 being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus.Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40 and 27.13 for CV-A16 (IQR: 23.15, 31.34, with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation. EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the

  13. Neutralizing antibody response in the patients with hand, foot and mouth disease to enterovirus 71 and its clinical implications

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    Zhu Liye

    2011-06-01

    Full Text Available Abstract Enterovirus 71 (EV71 has emerged as a significant pathogen causing large outbreaks in China for the past 3 years. Developing an EV71 vaccine is urgently needed to stop the spread of the disease; however, the adaptive immune response of humans to EV71 infection remains unclear. We examined the neutralizing antibody titers in HFMD patients and compared them to those of asymptomatic healthy children and young adults. We found that 80% of HFMD patients became positive for neutralizing antibodies against EV71 (GMT = 24.3 one day after the onset of illness. The antibody titers in the patients peaked two days (GMT = 79.5 after the illness appeared and were comparable to the level of adults (GMT = 45.2. Noticeably, the antibody response was not correlated with disease severity, suggesting that cellular immune response, besides neutralizing antibodies, could play critical role in controlling the outcome of EV71 infection in humans.

  14. Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China.

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    Xiaomei Wang

    Full Text Available Human enterovirus 71 (EV71-associated hand, foot, and mouth disease (HFMD has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV. Classified as EV71 subtype C4 (EV71 C4, these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1 of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3 showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5'UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD.

  15. MR Imaging Features of Acute Enterovirus 71 Encephalitis in a Patient with Hand-Foot-Mouth Disease: A Case Report

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    Park, Byung Sa; Yu, In Kyu; Lee, Byung Hee [Eulji University Hospital, Daejeon (Korea, Republic of)

    2011-02-15

    We report here on the MR findings of the first Korean case of hand-foot-mouth disease (HFMD) complicated by acute enterovirus 71 (EV 71) encephalitis in a 33-month old girl. Conventional MR images of the patient showed the increased signal intensity (SI) on a T2-weighted image (WI) at the posterior aspect of the medulla, the pontine tegmen, the bilateral dentate nuclei of the cerebellum and the midbrain. There was no evidence of abnormal SI or contrast enhancement at the same areas of the brain on the pre- and post-contrast T1-WI. The diffusion weighted images (DWI) also revealed the bilateral symmetrical strong high SI at the posterior aspect of the medulla and pontine tegmen and there was low SI at the same areas on the apparent diffusion coefficient (ADC) map. DWI in addition to the conventional MR imaging may be helpful for the early detection of acute EV 71 encephalitis in a patient with HFMD

  16. Structure determination of enterovirus 71

    Energy Technology Data Exchange (ETDEWEB)

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G. (Purdue); (Sentinext)

    2013-02-20

    Enterovirus 71 is a picornavirus that causes hand, foot and mouth disease but may induce fatal neurological illness in infants and young children. Enterovirus 71 crystallized in a body-centered orthorhombic space group with two particles in general orientations in the crystallographic asymmetric unit. Determination of the particle orientations required that the locked rotation function excluded the twofold symmetry axes from the set of icosahedral symmetry operators. This avoided the occurrence of misleading high rotation-function values produced by the alignment of icosahedral and crystallographic twofold axes. Once the orientations and positions of the particles had been established, the structure was solved by molecular replacement and phase extension.

  17. Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in Korea, 2009

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    Hye Kyung Cho

    2010-05-01

    Full Text Available Purpose : Hand-foot-mouth disease (HFMD is a common viral illness in children, which is usually mild and self-limiting. However, in recent epidemics of HFMD in Asia, enterovirus 71 (EV71 has been recognized as a causative agent with severe neurological symptoms with or without cardiopulmonary involvement. HFMD was epidemic in Korea in the spring of 2009. Severe cases with complications including death have been reported. The clinical characteristics in children with neurologic manifestations of EV71 were studied in Ewha Womans University Mokdong Hospital. Methods : Examinations for EV71 were performed from the stools, respiratory secretion or CSF of children who presented neurologic symptoms associated with HFMD by realtime PCR. Clinical and radiologic data of the patients were collected and analyzed. Results : EV71 was isolated from the stool of 16 patients but not from respiratory secretion or CSF. Among the 16 patients, meningitis (n=10 was the most common manifestation, followed by Guillain-Barr&eacute; syndrome (n=3, meningoencephalitis (n=2, poliomyelitis-like paralytic disease (n=1, and myoclonus (n=1. Gene analysis showed that most of them were caused by EV71 subgenotype C4a, which was prevalent in China in 2008. Conclusion : Because EV71 causes severe complications and death in children, a surveillance system to predict upcoming outbreaks should be established and maintained and adequate public health measures are needed to control disease.

  18. Clinical and neuroimaging features of enterovirus71 related acute flaccid paralysis in patients with hand-foot-mouth disease

    Institute of Scientific and Technical Information of China (English)

    Feng Chen; Jian-Jun Li; Tao Liu; Guo-Qiang Wen; Wei Xiang

    2013-01-01

    Objective: To investigate clinical and neuroimaging features of enterovirus71 (EV71) related acute flaccid paralysis in patients with hand-foot-mouth disease. Methods: Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012. Results: One extremity flaccid was found in four cases (3 with lower limb, 1 with upper limb), two limbs flaccid in three cases (2 with lower limbs, 1 with upper limbs), and four limbs flaccid in two cases. Spinal MRI studies showed lesion with high signal in T2-weighted images (T2WI) and low signal T1-weighted images (T1WI) in the spinal cord of all nine cases, and the lesions were mainly in bilateral and unilateral anterior horn of cervical spinal cord and spinal cord below thoracic 9 (T9) level. In addition, the midbrain, pons, and medulla, which were involved in 3 cases with brainstem encephalitis, demonstrated abnormal signal. Moreover, spinal cord contrast MRI studies showed mild enhancement in corresponding anterior horn of the involved side, and strong enhancement in its ventral root. Conclusions:EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior horn regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiently show the characteristic pattern and extent of the lesions which correlated well with the clinical features.

  19. Epidemiologic Features of Enterovirus 71-Associated Hand-Foot-and-Mouth Disease from 2009 to 2013 in Zhejiang, China

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    Zhifang Wang

    2016-12-01

    Full Text Available Enterovirus 71 (EV71 usually causes hand-foot-and-mouth disease (HFMD with severe clinical symptoms and even deaths in China. There is no efficient antiviral drug to protect against severe EV71-associated HFMD, making the development of EV71 vaccines therefore a priority. However, the potential target subject population(s to be immunized with EV71 vaccine are not well understood. In this study, we characterized the epidemiology regarding EV71-associated HFMD on the basis of provincial-level surveillance. We extracted data on EV71-associated HFMD from the National Notifiable Disease Reporting System in Zhejiang Province, China between 1 January 2009 and 31 December 2013 (n = 7650. The higher incidence rate of EV71 cases occurred in those children aged 12–23 months, with boys being predominant. Interestingly, different peaks activities of EV71 infection was observed in different calendar year, with one peak in 2009 and 2013 and two peaks in 2010–2012. However, EV71 infection seemed to predominately occur in warm season and a distinguished cyclic peak that seemed to be of about 12 months. Children aged 12–23 months are thus identified as an important target population for public health intervention, for example, it is recommended that these key subjects immunized with EV71 vaccine. In addition, an enhanced surveillance system for EV71-associated with HFMD needs to focus on generic and phylogenetic analysis.

  20. Epidemiologic Features of Enterovirus 71-Associated Hand-Foot-and-Mouth Disease from 2009 to 2013 in Zhejiang, China

    Science.gov (United States)

    Wang, Zhifang; Lv, Huakun; Zhu, Wenming; Mo, Zhe; Mao, Guangming; Wang, Xiaofeng; Lou, Xiaoming; Chen, Yongdi

    2016-01-01

    Enterovirus 71 (EV71) usually causes hand-foot-and-mouth disease (HFMD) with severe clinical symptoms and even deaths in China. There is no efficient antiviral drug to protect against severe EV71-associated HFMD, making the development of EV71 vaccines therefore a priority. However, the potential target subject population(s) to be immunized with EV71 vaccine are not well understood. In this study, we characterized the epidemiology regarding EV71-associated HFMD on the basis of provincial-level surveillance. We extracted data on EV71-associated HFMD from the National Notifiable Disease Reporting System in Zhejiang Province, China between 1 January 2009 and 31 December 2013 (n = 7650). The higher incidence rate of EV71 cases occurred in those children aged 12–23 months, with boys being predominant. Interestingly, different peaks activities of EV71 infection was observed in different calendar year, with one peak in 2009 and 2013 and two peaks in 2010–2012. However, EV71 infection seemed to predominately occur in warm season and a distinguished cyclic peak that seemed to be of about 12 months. Children aged 12–23 months are thus identified as an important target population for public health intervention, for example, it is recommended that these key subjects immunized with EV71 vaccine. In addition, an enhanced surveillance system for EV71-associated with HFMD needs to focus on generic and phylogenetic analysis. PMID:28042848

  1. Implications of Age-Dependent Immune Responses to Enterovirus 71 Infection for Disease Pathogenesis and Vaccine Design.

    Science.gov (United States)

    Gantt, Soren; Yao, Lena; Kollmann, Tobias R; Casper, Corey; Zhang, Jing; Self, Steven G

    2013-06-01

    Epidemics of enterovirus serotype 71 (EV71) infection in Asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. Efforts are underway to develop an effective EV71 vaccine. However, the immunologic correlates of protection against EV71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. Severe disease and death typically occur only in young children, which is likely due in part to a lack of EV71-specific adaptive immunity but possibly also due to age-dependent hyperactive innate immune responses. Infants are the primary targets of EV71 vaccination strategies. Therefore, studies are needed to understand the interplay between age, immunopathology, and severity of EV71 infection to distinguish protective from harmful immune responses and to guide the development of effective EV71 vaccines. This review summarizes our current understanding and outlines the next steps forward. © The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. MRI of Enterovirus 71 myelitis with monoplegia

    Energy Technology Data Exchange (ETDEWEB)

    Shen, W.C. [Department of Radiology, and School of Medicine, China Medical College, China Medical College Hospital, Taiwan (Taiwan); Tsai, C.H. [Department of Paediatrics, and School of Medicine, China Medical College, China Medical College Hospital, Taiwan (Taiwan); Chiu, H.H. [Department of Paediatrics, China Medical College Hospital, No. 2 Yuh-Der Road, 407 Taichung, Taiwan (Taiwan); Chow, K.C. [Department of Medical Research, China Medical College Hospital, Taichung, Taiwan (Taiwan)

    2000-02-01

    We report two boys diagnosed as having herpangina and hand-foot-mouth disease complicated by monoplegia during the outbreak enterovirus infection in Taiwan in 1998. Enterovirus 71 was identified in the stool and throat swab; neither polio nor Coxsackie viruses was identified. MRI showed unilateral lesions in the anterior horns of the spinal cord at T11-12 and C2-5. Although the MRI findings and sites of these lesions were similar to those of poliovirus-associated poliomyelitis, the virological data indicated that these boys were infected with enterovirus type 71. (orig.)

  3. Detection of Enteroviruses in Influent and Effluent Flow Samples from Wastewater Treatment Plants in Italy.

    Science.gov (United States)

    Battistone, Andrea; Buttinelli, Gabriele; Bonomo, Paolo; Fiore, Stefano; Amato, Concetta; Mercurio, Pietro; Cicala, Antonella; Simeoni, Josef; Foppa, Adelheid; Triassi, Maria; Pennino, Francesca; Fiore, Lucia

    2014-03-01

    This study evaluated the presence and seasonal distribution of polio and other enteroviruses in four wastewater treatment plants in three cities in Italy, using different treatment systems. Detection of enteroviruses was carried out by virus isolation in cell cultures after concentration of water samples collected at both inlet and outlet of the treatment plants, following the methods described in the WHO guidelines. Viral serotypes isolated before and after water treatment were compared. Forty-eight non-polio enteroviruses were isolated from 312 samples collected at the inlet of the four wastewater treatment plants, 35 of which were Coxsackievirus type B (72.9 %) and 13 Echovirus (27.1 %). After treatment, 2 CVB3, 1 CVB5, and 1 Echo 6 were isolated. CVB3 and Echo 6 serotypes were also detected in samples collected at the inlet of the TP, in the same month and year. The high rate of detection of infectious enteroviruses in inlet sewage samples (30.1 %) indicates wide diffusion of these viruses in the populations linked to the collectors. The incomplete removal of infectious viruses following sewage treatment highlights possible risks for public health relate to treated waters discharge into the environment.

  4. Correlation of symptomatic enterovirus infection and later risk of allergic diseases via a population-based cohort study

    Science.gov (United States)

    Lee, Zon-Min; Huang, Ying-Hsien; Ho, Shu-Chen; Kuo, Ho-Chang

    2017-01-01

    Abstract Infants who are exposed to the rhinovirus or respiratory syncytial virus are at a higher risk of subsequently developing wheezing or asthma. This study aims to determine whether preschoolers with a history of symptomatic enterovirus infection are at an increased risk of developing allergic diseases or not. We used data from the Taiwan National Health Insurance Research Database from 1999 to 2006 for this nationwide population-based cohort study. The subsequent risks for allergic diseases, which included asthma (International Classification of Diseases [ICD]-9: 493.X), allergic rhinitis (AR; ICD-9 CM code 477.X), and atopic dermatitis (AD; ICD-9-CM code 691.X), were compared between herpangina (ICD-9: 074.0) and hand, foot, and mouth disease (HFMD; ICD-9: 074.3) throughout the follow-up period using the Cox proportional hazards model. In this database, 12,016 neonates were born between January 1999 and December 1999. Among them, we further evaluated 8337 subjects; 3267 children infected with either herpangina or HFMD served as the study cohort, and the other 5070 children made up the comparison cohort. Children in the herpangina group had a higher risk of developing AR and AD, with adjusted hazard ratios of 1.15 (1.02–1.30, 95% CI) and 1.38 (1.17–1.63. 95% CI), respectively, while children suffered from HFMD had decreased risks of asthma, with an adjusted hazard ratio of 0.76 (0.63–0.93, 95% CI). Children who previously suffered from herpangina experienced an increased risk of subsequently developing AD and AR. Meanwhile, children who had suffered from HFMD experienced a decrease in the subsequent occurrence of asthma compared to the general population. PMID:28121929

  5. Challenges to Licensure of Enterovirus 71 Vaccines

    OpenAIRE

    Min-Shi Lee; Fan-Chen Tseng; Jen-Ren Wang; Chia-Yu Chi; Pele Chong; Ih-Jen Su

    2012-01-01

    Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71), which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA) are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD). A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. S...

  6. The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development

    OpenAIRE

    Ping-Chin Chang; Shou-Chien Chen; Kow-Tong Chen

    2016-01-01

    Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms “enterovirus 71” and “epidemiology” or “pathogenesis” or “molecular epidemiology” or “vaccine” in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion arti...

  7. Clinical and enterovirus findings associated with acute flaccid paralysis in the Republic of Korea during the recent decade.

    Science.gov (United States)

    Kim, HyeJin; Kang, Byounghak; Hwang, Seoyeon; Lee, Sang Won; Cheon, Doo-Sung; Kim, Kisang; Jeong, Yong-Seok; Hyeon, Ji-Yeon

    2014-09-01

    Acute flaccid paralysis (AFP) is described as sudden onset of flaccid paralysis in one or more limbs in children caused by polioviruses (PVs). PV eradication is achieved through intensive immunization and AFP attentive surveillance, according to the World Health Organization. Since 1998, the Korea Centers for Disease Control and Prevention has conducted surveillance system. This is an overview of surveillance in the Republic of Korea during the 10-year period from 2002 to 2011. The surveillance system for wild PV eradication was conducted through reporting and laboratory testing. Cell culture isolates were identified by neutralization tests using standard polyclonal antisera typing. The molecular methods were used for further characterization to improve specificity. For genotyping, semi-nested RT-PCR was used to amplify part of the viral protein 1 gene. Patients below 5 years of age accounted for the largest proportion of cases, and a positive association between age and incidence was found. In the total 285 cases, Guillain-Barré syndrome was the major leading causes of AFP. Non-polio enterovirus was detected in some AFP patients. EV71 was detected in 21 cases and Coxsackievirus (C) A2, CA6, CA9, CB2, CB3, CB4, CB5, and Echovirus (E) 25, E30, Sabin strain polio 2, polio 1 and 3 were also detected in some patients. The present study represents a comprehensive 10-year country-based survey of AFP in the Republic of Korea. This surveillance could provide better understanding of the epidemiologic pattern, and clinical manifestations associated with specific genotypes of AFP in the Republic of Korea.

  8. Identification of Enterovirus C105 for the first time in New Zealand

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    Angela Todd

    2015-02-01

    Full Text Available We report on the first identification of Enterovirus C105 (EV-C105 in New Zealand from a 52-year-old male hospitalized with mild respiratory tract symptoms. Enterovirus genotyping was performed by partial sequencing of the VP1 region of the enterovirus genome. This highlights the importance of enterovirus surveillance for detection of the importation of new genotypes such as EV-C105, thus allowing a better understanding of the roles they play in disease.

  9. An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

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    Sun Junling

    2010-05-01

    Full Text Available Abstract Hand, foot and mouth disease (HFMD, a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71 with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50% were hospitalized, 353 (5.8% were severe and 22 (0.36% were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16, resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.

  10. Enterovirus 71 Virus Propagation and Purification

    OpenAIRE

    Kristin L Shingler; Organtini, Lindsey J.; Hafenstein, Susan

    2014-01-01

    Since its discovery in 1969, enterovirus 71 (EV71) has emerged as a serious worldwide health threat. This member of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. This is the propagation and purification procedure to produce infectious virion.

  11. Enterovirus D68 Infection

    Directory of Open Access Journals (Sweden)

    Susanna Esposito

    2015-11-01

    Full Text Available First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68 is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many reports from different countries have described an increasing number of patients with respiratory diseases due to EV-D68 associated with relevant clinical severity. In particular, an unexpectedly high number of children have been hospitalized for severe respiratory disease due to EV-D68, requiring intensive care such as intubation and mechanical ventilation. Moreover, EV-D68 has been associated with acute flaccid paralysis and cranial nerve dysfunction in children, which has caused concerns in the community. As no specific antiviral therapy is available, treatment is mainly supportive. Moreover, because no vaccines are available, conventional infection control measures (i.e., standard, for contacts and droplets in both community and healthcare settings are recommended. However, further studies are required to fully understand the real importance of this virus. Prompt diagnosis and continued surveillance of EV-D68 infections are essential to managing and preventing new outbreaks. Moreover, if the association between EV-D68 and severe diseases will be confirmed, the development of adequate preventive and therapeutic approaches are a priority.

  12. Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.

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    Yan Zhang

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD. This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity. METHODOLOGY: Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined. PRINCIPAL FINDINGS: Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1 GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2 G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3 IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4 FACS analysis revealed that the frequency of CD19(+HLADR(+ mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.

  13. ENTEROVIRUS INFECTION: VARIETY OF ETIOLOGICAL FACTORS AND CLINICAL MANIFESTATIONS

    Directory of Open Access Journals (Sweden)

    O. I. Kanaeva

    2014-01-01

    Full Text Available Abstract. Enteroviruses are widely distributed human infectious pathogens. In spite of infection a disease does not manifest in majority number of cases. However, in some infected persons the different kind of symptoms can be observed; from common cold signs up to  aseptic (serous meningitis and myocarditis. Severe enteroviral cases with lethal outcomes are rarely reported. Ability of enteroviruses to cause large outbreaks and even epidemic distribution is very significant for health care systems. Taking in account a high genetic diversity of enteroviruses it is possible appearance of new highly pathogenic strains in the future. In some countries including the Russian Federation the permanent surveillance for enteroviral infections is provided besides of WHO polio elimination program. The laboratory diagnostics of enterovirus infections is complicated by numerous of pathogen serotypes. Thus, classical virological methods should be supported by molecular-biological tools to sequence pathogen genome and to define phylogenetic relations between different enterovirus strains.

  14. Molecular epidemiology of human enterovirus 71 at the origin of an epidemic of fatal hand, foot and mouth disease cases in Cambodia.

    Science.gov (United States)

    Duong, Veasna; Mey, Channa; Eloit, Marc; Zhu, Huachen; Danet, Lucie; Huang, Zhong; Zou, Gang; Tarantola, Arnaud; Cheval, Justine; Perot, Philippe; Laurent, Denis; Richner, Beat; Ky, Santy; Heng, Sothy; Touch, Sok; Sovann, Ly; van Doorn, Rogier; Tan Tran, Thanh; Farrar, Jeremy J; Wentworth, David E; Das, Suman R; Stockwell, Timothy B; Manuguerra, Jean-Claude; Delpeyroux, Francis; Guan, Yi; Altmeyer, Ralf; Buchy, Philippe

    2016-09-21

    Human enterovirus 71 (EV-A71) causes hand, foot and mouth disease (HFMD). EV-A71 circulates in many countries and has caused large epidemics, especially in the Asia-Pacific region, since 1997. In April 2012, an undiagnosed fatal disease with neurological involvement and respiratory distress occurred in young children admitted to the Kantha Bopha Children's Hospital in Phnom Penh, Cambodia. Most died within a day of hospital admission, causing public panic and international concern. In this study, we describe the enterovirus (EV) genotypes that were isolated during the outbreak in 2012 and the following year. From June 2012 to November 2013, 312 specimens were collected from hospitalized and ambulatory patients and tested by generic EV and specific EV-A71 reverse transcription PCR. EV-A71 was detected in 208 clinical specimens while other EVs were found in 32 patients. The VP1 gene and/or the complete genome were generated. Our phylogenetic sequencing analysis demonstrated that 80 EV-A71 strains belonged to the C4a subgenotype and 3 EV-A71 strains belonged to the B5 genotype. Furthermore, some lineages of EV-A71 were found to have appeared in Cambodia following separate introductions from neighboring countries. Nineteen EV A (CV-A6 and CV-A16), 9 EV B (EV-B83, CV-B3, CV-B2, CV-A9, E-31, E-2 and EV-B80) and 4 EV C (EV-C116, EV-C96, CV-A20 and Vaccine-related PV-3) strains were also detected. We found no molecular markers of disease severity. We report here that EV-A71 genotype C4 was the main etiological agent of a large outbreak of HFMD and particularly of severe forms associated with central nervous system infections. The role played by other EVs in the epidemic could not be clearly established.

  15. 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.

    Science.gov (United States)

    Lim, C T K; Jiang, L; Ma, S; James, L; Ang, L W

    2016-04-01

    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 based on the cumulative number of reported cases in the initial growth phase of each outbreak associated with the particular enterovirus type. A total of 33 HFMD outbreaks were selected based on the inclusion criteria specified for our study, of which five were associated with CV-A6, 13 with CV-A16, and 15 with EV-A71. The median R 0 was estimated to be 5·04 [interquartile range (IQR) 3·57-5·16] for CV-A6, 2·42 (IQR 1·85-3·36) for CV-A16, and 3·50 (IQR 2·36-4·53) for EV-A71. R 0 was not significantly associated with number of infected children (P = 0·86), number of exposed children (P = 0·94), and duration of the outbreak (P = 0·05). These enterovirus-specific R 0 estimates will be helpful in providing insights into the potential growth of future HFMD epidemics and outbreaks for timely implementation of disease control measures, together with disease dynamics such as severity of the cases.

  16. The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development

    Science.gov (United States)

    Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

    2016-01-01

    Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms “enterovirus 71” and “epidemiology” or “pathogenesis” or “molecular epidemiology” or “vaccine” in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing. PMID:27618078

  17. The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development

    Directory of Open Access Journals (Sweden)

    Ping-Chin Chang

    2016-09-01

    Full Text Available Enterovirus 71 (EV71 infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms “enterovirus 71” and “epidemiology” or “pathogenesis” or “molecular epidemiology” or “vaccine” in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4 that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

  18. The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development.

    Science.gov (United States)

    Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

    2016-09-09

    Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

  19. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice

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    Elizabeth A. Caine

    2015-11-01

    Full Text Available Hand, foot, and mouth disease (HFMD has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71 and Coxsackievirus A16 (CVA16 are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6, can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN α/β (A129 and α/β and γ (AG129 receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6 and 12 week-old AG129 (CVA16 mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  20. Alteration of serum high-mobility group protein 1 (HMGB1) levels in children with enterovirus 71-induced hand, foot, and mouth disease.

    Science.gov (United States)

    Zheng, Weikun; Shi, Haifan; Chen, Yiping; Xu, Zhiwei; Chen, Jie; Jin, Longteng

    2017-04-01

    Hand, foot, and mouth disease (HFMD) is a common pediatric disease caused by enterovirus infection. It typically presents as a fever along with flat, discolored spots and bumps on the hands, feet, and mouth. Compared with other viruses, enterovirus 71 (EV71)-induced HFMD is more prone to cause severe complications in children, such as brainstem encephalitis, cardiopulmonary disorders, and even death. More in-depth studies are still necessary to understand the characteristics of EV71-induced HFMD, although some related research has been reported so far. High-mobility group box 1 (HMGB1) is an inflammatory cytokine that can upregulate other inflammatory factors through its receptors, such as Toll-like receptors and the receptor for advanced glycation endproducts.We prospectively investigated the alteration of serum HMGB1, interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels before and after treatment in 82 children with HFMD.We found that the serum HMGB1, IL-6, and TNF-α levels were significantly increased in EV71-induced HFMD, and that these changes were more serious in the severe and critical HMFD groups; however, there was no significant difference in the HMGB1 level between the normal control and mild HMFD groups. Moreover, the serum HMGB1 level was positively correlated with the alteration of serum IL-6 and TNF-α concentrations.These results suggest that HMGB1 is involved in the inflammatory pathogenesis of EV71-induced HFMD and that the serum level of HMGB1 could be applied as a clinical indicator for the severity of HFMD, and also a sign for the recovery prognosis of HFMD.

  1. Co-circulation and genomic recombination of coxsackievirus A16 and enterovirus 71 during a large outbreak of hand, foot, and mouth disease in Central China.

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    Weiyong Liu

    Full Text Available A total of 1844 patients with hand, foot, and mouth disease (HFMD, most of them were children of age 1-3-year-old, in Central China were hospitalized from 2011 to 2012. Among them, 422 were infected with coxsackievirus A16 (CVA16, 334 were infected with enterovirus 71 (EV71, 38 were co-infected with EV71 and CVA16, and 35 were infected with other enteroviruses. Molecular epidemiology analysis revealed that EV71 and CVA16 were detected year-round, but EV71 circulated mainly in July and CVA16 circulated predominantly in November, and incidence of HFMD was reduced in January and February and increased in March. Clinical data showed that hyperglycemia and neurologic complications were significantly higher in EV71-infected patients, while upper respiratory tract infection and C-reactive protein were significantly higher in CVA16-associated patients. 124 EV71 and 80 CVA16 strains were isolated, among them 56 and 68 EV71 strains were C4a and C4b, while 25 and 55 CVA16 strains were B1a and B1b, respectively. Similarity plots and bootscan analyses based on entire genomic sequences revealed that the three C4a sub-genotype EV71 strains were recombinant with C4b sub-genotype EV71 in 2B-2C region, and the three CVA16 strains were recombinant with EV71 in 2A-2B region. Thus, CVA16 and EV71 were the major causative agents in a large HFMD outbreak in Central China. HFMD incidence was high for children among household contact and was detected year-round, but outbreak was seasonal dependent. CVA16 B1b and EV71 C4b reemerged and caused a large epidemic in China after a quiet period of many years. Moreover, EV71 and CVA16 were co-circulated during the outbreak, which may have contributed to the genomic recombination between the pathogens. It should gain more attention as there may be an upward trend in co-circulation of the two pathogens globally and the new role recombination plays in the emergence of new enterovirus variants.

  2. Identification of a Common Epitope between Enterovirus 71 and Human MED25 Proteins Which May Explain Virus-Associated Neurological Disease

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    Peihu Fan

    2015-03-01

    Full Text Available Enterovirus 71 (EV71 is a major causative pathogen of hand, foot and mouth disease with especially severe neurologic complications, which mainly account for fatalities from this disease. To date, the pathogenesis of EV71 in the central neurons system has remained unclear. Cytokine-mediated immunopathogenesis and nervous tissue damage by virus proliferation are two widely speculated causes of the neurological disease. To further study the pathogenesis, we identified a common epitope (co-epitope between EV71 VP1 and human mediator complex subunit 25 (MED25 highly expressed in brain stem. A monoclonal antibody (2H2 against the co-epitope was prepared, and its interaction with MED25 was examined by ELISA, immunofluorescence assay and Western blot in vitro and by live small animal imaging in vivo. Additionally, 2H2 could bind to both VP1 and MED25 with the affinity constant (Kd of 10−7 M as determined by the ForteBio Octet System. Intravenously injected 2H2 was distributed in brain stem of mice after seven days of EV71 infection. Interestingly, 2H2-like antibodies were detected in the serum of EV71-infected patients. These findings suggest that EV71 infection induces the production of antibodies that can bind to autoantigens expressed in nervous tissue and maybe further trigger autoimmune reactions resulting in neurological disease.

  3. Research Progress in Hand-Foot-Mouth Disease Caused by Severe Enterovirus 71 Infection%重症肠道病毒71型感染手足口病研究进展

    Institute of Scientific and Technical Information of China (English)

    郭靖

    2015-01-01

    常见的手足口病由重症肠道病毒71型引起,并在世界范围内流行。为了更加科学地认识肠道病毒71型与手足口病的关系,该文就重症肠道病毒71型引起的手足口病的病原学、发病机制、临床症状、流行病学、预防与诊治等方面的研究进展进行了综述。%Common hand-foot-mouth disease is caused by the severe enterovirus 71, and is prevalent around the world. In order to more scientifically understand the relationship between enterovirus 71 and hand-foot-mouth disease, this paper conducts the detailed review on the research progress of the severe enterovirus 71 caused hand-foot-mouth disease in the aspects of the etiology, pathogenesis, clinical symptom, epidemiology, prevention and treatment.

  4. Enterovirus D68 Infection

    NARCIS (Netherlands)

    Esposito, Susanna; Bosis, Samantha; Niesters, Hubert; Principi, Nicola

    2015-01-01

    First described in 1962 in children hospitalized for pneumonia and bronchiolitis, the Enterovirus D68 (EV-D68) is an emergent viral pathogen. Since its discovery, during the long period of surveillance up to 2005, EV-D68 was reported only as a cause of sporadic outbreaks. In recent years, many repor

  5. Enterovirus 71 Outbreak, Brunei

    OpenAIRE

    AbuBakar, Sazaly; Sam, I-Ching; Yusof, Jaliha; Lim, Meng Keang; Misbah, Suzana; ,; Hooi, Poh-Sim

    2009-01-01

    Enterovirus 71 (EV71) outbreaks occur periodically in the Asia-Pacific region. In 2006, Brunei reported its first major outbreak of EV71 infections, associated with fatalities from neurologic complications. Isolated EV71 strains formed a distinct lineage with low diversity within subgenogroup B5, suggesting recent introduction and rapid spread within Brunei.

  6. Enterovirus 71 infection and vaccines

    Science.gov (United States)

    2017-01-01

    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 paralysis that can be fatal. HFMD is most commonly caused by infection with coxsackievirus A16, and secondly by enterovirus 71 (EV71). Many other strains of coxsackievirus and enterovirus can also cause HFMD. Importantly, HFMD caused by EV71 tends to be associated with fatal complications. Therefore, there is an urgent need to protect against EV71 infection. Development of vaccines against EV71 would be the most effective approach to prevent EV71 outbreaks. Here, we summarize EV71 infection and development of vaccines, focusing on current scientific and clinical progress. PMID:28168168

  7. Antiviral Effect of Matrine against Human Enterovirus 71

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    Jiangning Liu

    2012-08-01

    Full Text Available Human enterovirus 71, a member of the Picornaviridae family, is one of the major causative agent of hand, foot and mouth disease in children less than six years old. This illness has caused mortalities in large-scale outbreaks in the Asia-Pacific region in recent years. No vaccine or antiviral therapy is available. In this study, antiviral effect of matrine against enterovirus 71 were evaluated in vitro and in vivo. Matrine could suppress the viral RNA copy number on rhabdomyosarcoma cells. Moreover, matrine treatment of mice challenged with a lethal dose of enterovirus 71 reduced the mortality and relieved clinical symptoms. The results showed that matrine may represent a potential therapeutic agent for enterovirus 71 infection.

  8. ENTEROVIRUS INFECTION IN CHILDREN: CLINICAL AND EPIDEMIOLOGICAL FEATURES AT THE CURRENT STAGE

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    G. P. Martynova

    2016-01-01

    Full Text Available The article presents the current clinical and epidemiological features of enterovirus infection in children of Krasnoyarsk Territory. A retrospective analysis of the incidence of enterovirus infection and enterovirus meningitis in the period 2014—2015 according to the forms of state statistical reporting №2 «Information on infectious and parasitic diseases». Clinical and epidemiological analysis of enterovirus infection in 454 children who were treated at MBUZ «City Children's Infectious Hospital №1» in the period of seasonal rise of morbidity in 2014 revealed a prevalence of etiological structure of enteroviruses Coxsackie B, Coxsackie B5, Coxsackie B3, Coxsackie B4. The region recorded the different clinical forms of enterovirus infection (rash, myalgia, diarrhea, gerpangina, the structure of which is still, aseptic meningitis prevails.

  9. The complete genome of Enterovirus 71 China strain

    Institute of Scientific and Technical Information of China (English)

    YANG; Fan

    2001-01-01

    [1]Jin Qi, Medical Molecular Virology (in Chinese), Beijing: Science Press, 2001.[2]McMinn, P., Stratov, I., Dowse, G., Enterovirus 71 outbreak in Western Australia associated with acute flaccid paralysis, Preliminary report, Commun. Dis. Intell., 1999, 23(7): 199.[3]Ho, M., Chen, E. R., Hsu, K. H. et al., An epidemic of Enterovirus 71 infection in Taiwan, The New England Journal of Medicine, 1999, 341(13): 929.[4]He Yaqing, Yang Fan, Li Chengliang et al., Identification of EV71 isolates from hand, foot and mouth disease cases in ShenZhen, Chinese Journal of Experimental and Clinical Virology (in Chinese), 1999, 1: 112.[5]Landry, M. L., Fonseca, S. N. S., Cohen, S. et al., Fatal enterovirus type 71 infection: rapid detection and diagnostic pitfalls, Pediatr. Infect. Dis. J., 1995, 14: 1095.[6]Brown, B. A., Pallansch, M. A., Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus, Virus Res., 1995, 39: 195.[7]Brown, B. A., Oberste, M. S., Alexander, J. P. Jr., Molecular epidemiology and evolution of Enterovirus 71 strains isolated from 1970 to 1998, J. Virol., 1999, 73(12): 9969.[8]Ishimaru,Y., Nakano,S., Yamaoda,K.et al.,Outbreaks of hand,foot,and mouth disease by Enterovirus 71,Arch.Dis.Child.,1980,55:583.

  10. 手足口病(EV71)防治%Prevetion and Treatment of Hand-foot-mouth Disease(enterovirus 71)

    Institute of Scientific and Technical Information of China (English)

    田玲; 汪楠; 张宏梁; 张黎黎

    2008-01-01

    1手足口病概况1.1手足口病手足口病[1](Hand-foot-mouth disease,HFMD)是由多种肠道病毒引起的常见传染病,是全球性传染病,世界大部分地区均有此病流行的报道。1957年新西兰首次报道该病,1958年分离出柯萨奇病毒,1959年命名为手足口病。该病以婴幼儿发病为主。大多数患者症状轻微,以发热和手、足、口腔等部位的皮疹或疱疹为主要特征。少数患者可以并发无菌性脑膜炎、脑炎、急性弛缓性麻痹、呼吸道感染和心肌炎等,个别重症患儿病情进展快,易发生死亡。少年儿童和成人感染后多不发病,但能够传播病毒。手足口病绝大多数情况下7~10d可以自行痊愈,不会留下后遗症,皮肤上也不会留下瘢痕。个别重症患者可能出现脑膜炎、肺炎等,只要积极配合医生治疗,多数可以痊愈。1.2手足口病与EV71EV71(enterovirus71,EV71)是小RNA病毒科(Picomaviridae)肠道病毒属(Enterovirus)成员。EV71感染除了引起手足口病病以外,还能够引起无菌性脑膜炎(aseptic meningitis)、脑干脑炎(brain-stemencephalitis)和脊髓灰质炎样的麻痹(poliom...

  11. Serum microRNA expression profile distinguishes enterovirus 71 and coxsackievirus 16 infections in patients with hand-foot-and-mouth disease.

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    Lunbiao Cui

    Full Text Available Altered circulating microRNA (miRNA profiles have been noted in patients with microbial infections. We compared host serum miRNA levels in patients with hand-foot-and-mouth disease (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 as well as in other microbial infections and in healthy individuals. Among 664 different miRNAs analyzed using a miRNA array, 102 were up-regulated and 26 were down-regulated in sera of patients with enteroviral infections. Expression levels of ten candidate miRNAs were further evaluated by quantitative real-time PCR assays. A receiver operating characteristic (ROC curve analysis revealed that six miRNAs (miR-148a, miR-143, miR-324-3p, miR-628-3p, miR-140-5p, and miR-362-3p were able to discriminate patients with enterovirus infections from healthy controls with area under curve (AUC values ranged from 0.828 to 0.934. The combined six miRNA using multiple logistic regression analysis provided not only a sensitivity of 97.1% and a specificity of 92.7% but also a unique profile that differentiated enterovirial infections from other microbial infections. Expression levels of five miRNAs (miR-148a, miR-143, miR-324-3p, miR-545, and miR-140-5p were significantly increased in patients with CVA16 versus those with EV71 (p<0.05. Combination of miR-545, miR-324-3p, and miR-143 possessed a moderate ability to discrimination between CVA16 and EV71 with an AUC value of 0.761. These data indicate that sera from patients with different subtypes of enteroviral infection express unique miRNA profiles. Serum miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping enteroviral HFMD infections.

  12. Cellular receptors for human enterovirus species A

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    Yorihiro eNishimura

    2012-03-01

    Full Text Available Human enterovirus species A (HEV-A is one of the four species of HEV in the genus Enterovirus in the family Picornaviridae. Among HEV-A, coxsackievirus A16 (CVA16 and enterovirus 71 (EV71 are the major causative agents of hand, foot, and mouth disease (HFMD. Some other types of HEV-A are commonly associated with herpangina. Although HFMD and herpangina due to HEV-A are common febrile diseases among infants and children, EV71 can cause various neurological diseases, such as aseptic meningitis and fatal encephalitis.Recently, two human transmembrane proteins, P-selectin glycoprotein ligand-1 (PSGL-1 and scavenger receptor class B, member 2 (SCARB2, were identified as functional receptors for EV71 and CVA16. In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and SCARB2 could be responsible for the specific receptors for EV71 and CVA16. However, the involvement of both receptors in the in vitro and in vivo infections of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse array of the clinical outcome of HEV-A-associated diseases, the identification and characterization of HEV-A receptors may provide useful information in understanding the HEV-A pathogenesis at a molecular level.

  13. Challenges to licensure of enterovirus 71 vaccines.

    Directory of Open Access Journals (Sweden)

    Min-Shi Lee

    Full Text Available Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71, which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD. A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design.

  14. Combining Multiplex Reverse Transcription-PCR and a Diagnostic Microarray To Detect and Differentiate Enterovirus 71 and Coxsackievirus A16

    OpenAIRE

    Chen, Tsan-Chi; Chen, Guang-Wu; Hsiung, Chao Agnes; Yang, Jyh-Yuan; Shih, Shin-Ru; Lai, Yiu-Kay; Juang, Jyh-Lyh

    2006-01-01

    Cluster A enteroviruses, including enterovirus 71 (EV71) and coxsackievirus A16 (CA16), are known to cause hand-foot-and-mouth disease (HFMD). Despite the close genetic relationship between these two viruses, EV71 is generally known to be a more perpetuating pathogen involved in severe clinical manifestations and deaths. While the serotyping of enteroviruses is mostly done by conventional immunological methods, many clinical isolates remain unclassifiable due to the limited number of antibodi...

  15. Deferoxamine Compensates for Decreases in B Cell Counts and Reduces Mortality in Enterovirus 71-Infected Mice

    Directory of Open Access Journals (Sweden)

    Yajun Yang

    2014-07-01

    Full Text Available Enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. No vaccine or antiviral therapy is currently available. In this work, we found that the number of B cells was reduced in enterovirus 71-infected mice. Deferoxamine, a marine microbial natural product, compensated for the decreased levels of B cells caused by enterovirus 71 infection. The neutralizing antibody titer was also improved after deferoxamine treatment. Furthermore, deferoxamine relieved symptoms and reduced mortality and muscle damage caused by enterovirus 71 infection. This work suggested that deferoxamine has the potential for further development as a B cell-immunomodulator against enterovirus 71.

  16. VIRO-TypeNed, systematic molecular surveillance of enteroviruses in the Netherlands between 2010 and 2014.

    Science.gov (United States)

    Benschop, Kimberley S M; Rahamat-Langendoen, Janette C; van der Avoort, Harrie G A M; Claas, Eric C J; Pas, Suzan D; Schuurman, Rob; Verweij, Jaco J; Wolthers, Katja C; Niesters, Hubert G M; Koopmans, Marion P G

    2016-09-29

    VIRO-TypeNed is a collaborative molecular surveillance platform facilitated through a web-based database. Genetic data in combination with epidemiological, clinical and patient data are shared between clinical and public health laboratories, as part of the surveillance underpinning poliovirus eradication. We analysed the combination of data submitted from 2010 to 2014 to understand circulation patterns of non-polio enteroviruses (NPEV) of public health relevance. Two epidemiological patterns were observed based on VIRO-TypeNed data and classical surveillance data dating back to 1996: (i) endemic cyclic, characterised by predictable upsurges/outbreaks every two to four years, and (ii) epidemic, where rare virus types caused upsurges/outbreaks. Genetic analysis suggests continuous temporal displacement of virus lineages due to the accumulation of (silent) genetic changes. Non-synonymous changes in the antigenic B/C loop suggest antigenic diversification, which may affect population susceptibility. Infections were frequently detected at an age under three months and at an older, parenting age (25-49 years) pointing to a distinct role of immunity in the circulation patterns. Upsurges were detected in the summer and winter which can promote increased transmissibility underlying new (cyclic) upsurges and requires close monitoring. The combination of data provide a better understanding of NPEV circulation required to control and curtail upsurges and outbreaks. This article is copyright of The Authors, 2016.

  17. Genetic Determinants of Enterovirus Infections

    DEFF Research Database (Denmark)

    Witsø, Elisabet; Cinek, Ondrej; Tapia, German

    2015-01-01

    essentially all enterovirus serotypes, in 7,393 longitudinal stool samples collected monthly (age range 3-36 months). The most significant association was with two T1D SNPs, rs12150079 (ZPBP2/ORMDL3/GSDMB region) (enterovirus frequency: AA 7.3%, AG 8.7%, GG 9.7%, RR = 0.86, overall p = 1.87E-02) and rs229541...

  18. Epidemics and Frequent Recombination within Species in Outbreaks of Human Enterovirus B-Associated Hand, Foot and Mouth Disease in Shandong China in 2010 and 2011.

    Directory of Open Access Journals (Sweden)

    Ting Zhang

    Full Text Available The epidemiology and molecular characteristics of human enterovirus B (HEV-B associated with hand, foot and mouth disease (HFMD outbreaks in China are not well known. In the present study, we tested 201 HEV isolates from 233 clinical specimens from patients with severe HFMD during 2010-2011 in Linyi, Shandong, China. Of the 201 isolates, 189 were fully typed and 18 corresponded to HEV-B species (six serotypes CVA9, CVB1, CVB4, Echo 6, Echo 25 and Echo 30 using sensitive semi-nested polymerase chain reaction analysis of VP1 gene sequences. Phylogenetic analysis based on the VP1 region showed that eight E30SD belonged to a novel sub-genogroup D2; E25SD belonged to a novel sub-genogroup D6; E6SD belonged to sub-lineage C6 and five CVB1SD belonged to subgroup 4C; and B4SD belonged sub-lineage D2. The full viral genomes of the CVB1SD, E6SD, E25SD and E30SD isolates were sequenced. Analysis of phylogenetic and similarity plots indicated that E25SD recombined with E25-HN-2, E30FDJS03 and E4AUS250 at noncontiguous P2A-P3D regions, while E30SD, E30FDJ03, E25-HN-2 and E9 DM had shared sequences in discrete regions of P2 and P3. Both E6SD and B1SD shared sequences with E1-HN, B4/GX/10, B5-HN, and A9-Alberta in contiguous regions of most of P2 and P3. Genetic algorithm recombination detection analysis further confirmed the existence of multiple potential recombination points. In conclusion, analysis of the complete genomes of E25SD, E30SD, CVB1SD and E6SD isolated from HFMD patients revealed that they formed novel subgenogroup. Given the prevalence and recombination of these viruses in outbreaks of HFMD, persistent surveillance of HFMD-associated HEV-B pathogens is required to predict potential emerging viruses and related disease outbreaks.

  19. Prevalence of multiple enteroviruses associated with hand, foot, and mouth disease in Shijiazhuang City, Hebei province, China: outbreaks of coxsackieviruses a10 and b3.

    Directory of Open Access Journals (Sweden)

    Huifang Tian

    Full Text Available Hand, foot, and mouth disease (HFMD has been one of the most common infectious diseases in Shijiazhuang City, as is the situation in China overall. In the National HFMD surveillance system, the pathogen detection was focused on EV-A71 and CVA16, and therefore, information on the other EVs is very limited. In order to identify the circulating EV serotypes in the HFMD outbreaks in Shijiazhuang City during 2010-2012, 4045 patients presented with HFMD were recruited in the study, and clinical samples were investigated. Typing of EV serotypes was performed using the molecular typing methods, and phylogenetic analyses based on entire VP1 sequences of human enterovirus 71 (EV-A71, coxsackievirus A16 (CVA16, CVA10 and CVB3 was performed. The results revealed that EV-A71 and CVA16 were the 2 most important pathogens but the circulating trends of the 2 viruses showed a shift, the spread of EV-A71 became increasingly weak, whereas the spread of CVA16 became increasingly stronger. CVA10 and CVB3 were the third and fourth most prevalent pathogens, respectively. Co-infection of two viruses at the same time was not found in these samples. Based on entire VP1 region sequences, the phylogenetic analysis revealed that C4a subgenotype EV-A71, B1a and B1b subgenotype CVA16 continued to evolve. The CVA10 strains were assigned to 4 genotypes (A-D, whereas the CVB3 strains were assigned to 5 genotypes (A-E, with clear geographical and temporal-specific distributions. The Shijiazhuang CVA10 sequences belonged to 4 epidemic lineages within genotype C, whereas the Shijiazhuang CVB3 sequences belonged to 2 epidemic lineages within genotype E, which may have the same origins as the strains reported in other part of China. CVA10 and CVB3, 2 pathogens that were previously infrequently detected, were identified as pathogens causing the HFMD outbreaks. This study underscores the need for detailed laboratory-based surveillances of HFMD in mainland China.

  20. Characterization of Coxsackievirus A6- and Enterovirus 71-Associated Hand Foot and Mouth Disease in Beijing, China, from 2013 to 2015.

    Science.gov (United States)

    Li, Jie; Sun, Ying; Du, Yiwei; Yan, Yuxiang; Huo, Da; Liu, Yuan; Peng, Xiaoxia; Yang, Yang; Liu, Fen; Lin, Changying; Liang, Zhichao; Jia, Lei; Chen, Lijuan; Wang, Quanyi; He, Yan

    2016-01-01

    Etiology surveillance of Hand Foot and Mouth disease (HFMD) in Beijing showed that Coxsackievirus A6 (CVA6) became the major pathogen of HFMD in 2013 and 2015. In order to understand the epidemiological characteristics and clinical manifestations of CVA6-associated HFMD, a comparison study among CVA6-, EV71- (Enterovirus 71), and CVA16- (Coxsackievirus A16) associated HFMD was performed. Epidemiological characteristics and clinical manifestations among CVA6-, EV71- and CVA16-associated mild or severe cases were compared from 2013 to 2015. VP1 gene of CVA6 and EV71 from mild cases, severe cases were sequenced, aligned, and compared with strains from 2009 to 2015 in Beijing and strains available in GenBank. Phylogenetic tree was constructed by neighbor-joining method. CVA6 became the predominant causative agent of HFMD and accounted for 35.4 and 36.9% of total positive cases in 2013 and 2015, respectively. From 2013 to 2015, a total of 305 severe cases and 7 fatal cases were reported. CVA6 and EV71 were responsible for 57.5% of the severe cases. Five out six samples from fatal cases were identified as EV71. High fever, onychomadesis, and decrustation were the typical symptoms of CVA6-associated mild HFMD. CVA6-associated severe cases were characterized by high fever with shorter duration and twitch compared with EV71-associated severe cases which were characterized by poor mental condition, abnormal pupil, and vomiting. Poor mental condition, lung wet rales, abnormal pupil, and tachycardia were the most common clinical features of fatal cases. The percentage of lymphocyte in CVA6-associated cases was significantly lower than that of EV71. High percentage of lymphocyte and low percentage of neutrophils were the typical characteristics of fatal cases. VP1 sequences between CVA6- or EV71-associated mild and severe cases were highly homologous. CVA6 became one of the major pathogens of HFMD in 2013 and 2015 in Beijing. Epidemiological characteristics, clinical

  1. Synergistic antiviral activity of gemcitabine and ribavirin against enteroviruses

    NARCIS (Netherlands)

    Kang, Hyunju; Kim, Chonsaeng; Kim, Dong-Eun; Song, Jae-Hyoung; Choi, Miri; Choi, Kwangman; Kang, Mingu; Lee, Kyungjin; Kim, Hae Soo; Shin, Jin Soo; Kim, Janghwan; Han, Sang-Bae; Lee, Mi-Young; Lee, Su Ui; Lee, Chong-Kyo; Kim, Meehyein; Ko, Hyun-Jeong; van Kuppeveld, Frank J M; Cho, Sungchan

    2015-01-01

    Enteroviruses are major causative agents of various human diseases, and some of them are currently considered to be an enormous threat to public health. However, no effective therapy is currently available for the treatment of these infections. We identified gemcitabine, a nucleoside-analog drug use

  2. Severe neonatal parechovirus infection and similarity with enterovirus infection

    NARCIS (Netherlands)

    Verboon-Maciolek, Malgorzata A.; Krediet, Tannette G.; Gerards, Leo J.; de Vries, Linda S.; Groenendaal, Floris; van Loon, Anton M.

    Background: Enteroviruses (EV) are an important cause of neonatal disease including hepatitis, meningoencephalitis, and myocarditis that can lead to death or severe long-term sequelae. Less is known about severe neonatal infection caused by the parechoviruses (PeV) of which type 1 (PeV1) and type 2

  3. Accuracy of diagnostic methods and surveillance sensitivity for human enterovirus, South Korea, 1999-2011.

    Science.gov (United States)

    Hyeon, Ji-Yeon; Hwang, Seoyeon; Kim, Hyejin; Song, Jaehyoung; Ahn, Jeongbae; Kang, Byunghak; Kim, Kisoon; Choi, Wooyoung; Chung, Jae Keun; Kim, Cheon-Hyun; Cho, Kyungsoon; Jee, Youngmee; Kim, Jonghyun; Kim, Kisang; Kim, Sun-Hee; Kim, Min-Ji; Cheon, Doo-Sung

    2013-08-01

    The epidemiology of enteroviral infection in South Korea during 1999-2011 chronicles nationwide outbreaks and changing detection and subtyping methods used over the 13-year period. Of 14,657 patients whose samples were tested, 4,762 (32.5%) samples were positive for human enterovirus (human EV); as diagnostic methods improved, the rate of positive results increased. A seasonal trend of outbreaks was documented. Genotypes enterovirus 71, echovirus 30, coxsackievirus B5, enterovirus 6, and coxsackievirus B2 were the most common genotypes identified. Accurate test results correlated clinical syndromes to enterovirus genotypes: aseptic meningitis to echovirus 30, enterovirus 6, and coxsackievirus B5; hand, foot and mouth disease to coxsackievirus A16; and hand, foot and mouth disease with neurologic complications to enterovirus 71. There are currently no treatments specific to human EV infections; surveillance of enterovirus infections such as this study provides may assist with evaluating the need to research and develop treatments for infections caused by virulent human EV genotypes.

  4. Surveillance and analysis of human enterovirus in environmental water in Guizhou Province%贵州省环境水体肠道病毒监测分析

    Institute of Scientific and Technical Information of China (English)

    苏飞; 叶绪芳; 任刚; 王寅寅

    2014-01-01

    目的 研究贵州省环境水体中肠道病毒(Enterovirus,EV),尤其是脊髓灰质炎病毒(Poliovirus,PV)的感染和分布情况,为最终根除脊灰计划提供科学依据.方法 环境水样经浓缩处理后进行病毒分离、鉴定和核苷酸序列分析.结果 22份水样中检出阳性14份,阳性率为63.6%,其中PV 3株,非脊灰肠道病毒(Non-Polio Enterovirus,NPEV) 58株.结论 EV广泛存在环境水体中,分离出的3株PV均为疫苗株,未发生变异,未在环境及人群中发生循环,贵州省继续维持无脊灰状态.

  5. Class I ADP-ribosylation factors are involved in enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 is one of the major causative agents of hand, foot, and mouth disease in infants and children. Replication of enterovirus 71 depends on host cellular factors. The viral replication complex is formed in novel, cytoplasmic, vesicular compartments. It has not been elucidated which cellular pathways are hijacked by the virus to create these vesicles. Here, we investigated whether proteins associated with the cellular secretory pathway were involved in enterovirus 71 replication. We used a loss-of-function assay, based on small interfering RNA. We showed that enterovirus 71 RNA replication was dependent on the activity of Class I ADP-ribosylation factors. Simultaneous depletion of ADP-ribosylation factors 1 and 3, but not three others, inhibited viral replication in cells. We also demonstrated with various techniques that the brefeldin-A-sensitive guanidine nucleotide exchange factor, GBF1, was critically important for enterovirus 71 replication. Our results suggested that enterovirus 71 replication depended on GBF1-mediated activation of Class I ADP-ribosylation factors. These results revealed a connection between enterovirus 71 replication and the cellular secretory pathway; this pathway may represent a novel target for antiviral therapies.

  6. A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71

    Science.gov (United States)

    Wang, Xiangxi; Peng, Wei; Ren, Jingshan; Hu, Zhongyu; Xu, Jiwei; Lou, Zhiyong; Li, Xumei; Yin, Weidong; Shen, Xinliang; Porta, Claudine; Walter, Thomas S.; Evans, Gwyndaf; Axford, Danny; Owen, Robin; Rowlands, David J.; Wang, Junzhi; Stuart, David I.; Fry, Elizabeth E.; Rao, Zihe

    2012-01-01

    Enterovirus 71 (EV71), a major agent of hand-foot-and-mouth disease in children, can cause severe central nervous system disease and mortality. At present no vaccine or antiviral therapy is available. We have determined high-resolution structures for the mature virus and natural empty particles. The structure of the mature virus is similar to that of other enteroviruses, whilst the empty particles are dramatically expanded, with notable fissures, resembling elusive enterovirus uncoating intermediates not previously characterized in atomic detail. Hydrophobic capsid pockets within the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. The results provide a paradigm for enterovirus uncoating, in which the VP1 GH loop acts as an adaptor-sensor for the attachment of cellular receptors, converting heterologous inputs to a generic uncoating mechanism, spotlighting novel points for therapeutic intervention. PMID:22388738

  7. Development of a sensitive and specific epitope-blocking ELISA for universal detection of antibodies to human enterovirus 71 strains

    National Research Council Canada - National Science Library

    He, Fang; Kiener, Tanja K; Lim, Xiao Fang; Tan, Yunrui; Raj, Kattur Venkatachalam Ashok; Tang, Manli; Chow, Vincent T K; Chen, Qingfeng; Kwang, Jimmy

    2013-01-01

    Human Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease (HFMD) in young children. It is often associated with severe neurological diseases and mortalities in recent outbreaks across the Asia Pacific region...

  8. Structure determination of enterovirus 71

    OpenAIRE

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G

    2012-01-01

    Determination of the orientation of the enterovirus 71 virions in the crystal required the calculation of a locked rotation function that included only icosahedral threefold and fivefold symmetry axes. Otherwise, misleading high rotation-function values were produced by accidental alignment of icosahedral and crystallographic twofold axes.

  9. COPI is required for enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71, a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11, is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies.

  10. Development of Novel Vaccines against Enterovirus-71

    Directory of Open Access Journals (Sweden)

    Pinn Tsin Isabel Yee

    2015-12-01

    Full Text Available The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71 and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1 vaccine and virus-like particles (VLPs. The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design.

  11. 21 CFR 866.3225 - Enterovirus nucleic acid assay.

    Science.gov (United States)

    2010-04-01

    ... meningitis or meningoencephalitis. The detection of enterovirus RNA, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of viral meningitis caused by enterovirus....

  12. Enterovirus and herpesviridae family as etiologic agents of lymphomonocytary meningitis, Southern Brazil

    Directory of Open Access Journals (Sweden)

    Luine Rosele Renaud Vidal

    2011-06-01

    Full Text Available Viral meningitis is a common infectious disease of the central nervous system (CNS that occurs worldwide. The aim of this study was to identify the etiologic agent of lymphomonocytary meningitis in Curitiba, PR, Brazil. During the period of July 2005 to December 2006, 460 cerebrospinal fluid (CSF samples with lymphomonocytary meningitis were analyzed by PCR methodologies. Fifty nine (12.8% samples were positive. Enteroviruses was present in 49 (83% samples and herpes virus family in 10 (17%, of these 6 (10% herpes simplex virus, 1 (2% Epstein Barr virus, 2 (3% human herpes virus type 6 and 1 (2% mixed infection of enterovirus and Epstein Barr virus. As conclusion enterovirus was the most frequent virus, with circulation during summer and was observed with higher frequency between 4 to 17 years of age. PCR methodology is an important method for rapid detection of RNA enterovirus and DNA herpesvirus in CSF.

  13. Enterovirus and herpesviridae family as etiologic agents of lymphomonocytary meningitis, Southern Brazil.

    Science.gov (United States)

    Vidal, Luine Rosele Renaud; Almeida, Sérgio Monteiro de; Messias-Reason, Iara José de; Nogueira, Meri Bordignon; Debur, Maria do Carmo; Pessa, Luís Felipe Cavalli; Pereira, Luciane Aparecida; Rotta, Indianara; Takahashi, Gislene Reche de Almeida; Silveira, Clyete Santos da; Araújo, Josianne Maria Reimann; Raboni, Sonia Mara

    2011-06-01

    Viral meningitis is a common infectious disease of the central nervous system (CNS) that occurs worldwide. The aim of this study was to identify the etiologic agent of lymphomonocytary meningitis in Curitiba, PR, Brazil. During the period of July 2005 to December 2006, 460 cerebrospinal fluid (CSF) samples with lymphomonocytary meningitis were analyzed by PCR methodologies. Fifty nine (12.8%) samples were positive. Enteroviruses was present in 49 (83%) samples and herpes virus family in 10 (17%), of these 6 (10%) herpes simplex virus, 1 (2%) Epstein Barr virus, 2 (3%) human herpes virus type 6 and 1 (2%) mixed infection of enterovirus and Epstein Barr virus. As conclusion enterovirus was the most frequent virus, with circulation during summer and was observed with higher frequency between 4 to 17 years of age. PCR methodology is an important method for rapid detection of RNA enterovirus and DNA herpesvirus in CSF.

  14. Clinical Efficacy of Therapy with Recombinant Human Interferon α1b in Hand, Foot, and Mouth Disease with Enterovirus 71 Infection.

    Directory of Open Access Journals (Sweden)

    Xueyong Huang

    Full Text Available A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-α1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-α1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD.Chinese Clinical Trial Registry ChiCTR-TRC-14005153.

  15. Crystal Structure of Human Enterovirus 71

    Energy Technology Data Exchange (ETDEWEB)

    Plevka, Pavel; Perera, Rushika; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G. (Purdue); (Sentinext)

    2013-04-08

    Enterovirus 71 is a picornavirus associated with fatal neurological illness in infants and young children. Here, we report the crystal structure of enterovirus 71 and show that, unlike in other enteroviruses, the 'pocket factor,' a small molecule that stabilizes the virus, is partly exposed on the floor of the 'canyon.' Thus, the structure of antiviral compounds may require a hydrophilic head group designed to interact with residues at the entrance of the pocket.

  16. Therapeutic Use of Native and Recombinant Enteroviruses

    Directory of Open Access Journals (Sweden)

    Jani Ylä-Pelto

    2016-02-01

    Full Text Available Research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. Many of these “viral” receptors are overexpressed in cancer cells. Receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e., disruption of the cells. Viral tropism and cytolytic properties thus make native enteroviruses prime candidates for oncolytic virotherapy. Copy DNA cloning and modification of enterovirus genomes have resulted in the generation of enterovirus vectors with properties that are useful in therapy or in vaccine trials where foreign antigenic epitopes are expressed from or on the surface of the vector virus. The small genome size and compact particle structure, however, set limits to enterovirus genome modifications. This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy.

  17. Therapeutic Use of Native and Recombinant Enteroviruses.

    Science.gov (United States)

    Ylä-Pelto, Jani; Tripathi, Lav; Susi, Petri

    2016-02-23

    Research on human enteroviruses has resulted in the identification of more than 100 enterovirus types, which use more than 10 protein receptors and/or attachment factors required in cell binding and initiation of the replication cycle. Many of these "viral" receptors are overexpressed in cancer cells. Receptor binding and the ability to replicate in specific target cells define the tropism and pathogenesis of enterovirus types, because cellular infection often results in cytolytic response, i.e., disruption of the cells. Viral tropism and cytolytic properties thus make native enteroviruses prime candidates for oncolytic virotherapy. Copy DNA cloning and modification of enterovirus genomes have resulted in the generation of enterovirus vectors with properties that are useful in therapy or in vaccine trials where foreign antigenic epitopes are expressed from or on the surface of the vector virus. The small genome size and compact particle structure, however, set limits to enterovirus genome modifications. This review focuses on the therapeutic use of native and recombinant enteroviruses and the methods that have been applied to modify enterovirus genomes for therapy.

  18. Enterovirus 74 infection in children.

    Directory of Open Access Journals (Sweden)

    Matthew Peacey

    Full Text Available Enterovirus 74 (EV74 is a rarely detected viral infection of children. In 2010, EV74 was identified in New Zealand in a 2 year old child with acute flaccid paralysis (AFP through routine polio AFP surveillance. A further three cases of EV74 were identified in children within six months. These cases are the first report of EV74 in New Zealand. In this study we describe the near complete genome sequence of four EV74 isolates from New Zealand, which shows only limited sequence identity in the non-structural proteins when compared to the other two known EV74 sequences. As is typical of enteroviruses multiple recombination events were evident, particularly in the P2 region and P3 regions. This is the first complete EV74 genome sequenced from a patient with acute flaccid paralysis.

  19. The genom of enteroviruses in the blood serum of patients with acute stroke

    Directory of Open Access Journals (Sweden)

    Andryushkova N.G.

    2016-12-01

    Full Text Available Objective of the study was determination of enterovirus genom presence in the blood serum of patients with acute stroke by polymerase chain reaction (PCR. The blood serum of 72 patients with acute stroke and control group of 30 patients with another vascular disease was studied to reveal genom of enteroviruses. Detection of enterovirus RNA was performed by PCR using the reverse transcription. Viruses were isolated on HeLa and HEp-2 cell lines. The enterovirus genom detected by PCR was in 17 of 72 samples of the tested serum in the research group (23,6±5,0%. In the control group only one serum was PCR-positive for enteroviruses (3,3±3,2%. Cytopathogenic agents were isolated in HEp-2 and HeLa cell lines from 11 PCR-positive samples of blood serum from the experimental group of patients. No viruses were isolated from the remaining PCR-positive and PCR-negative sera. The presence of enteroviruses in the blood of patients with acute stroke suggests etiopathogenetical link between them. The introduction of PCR to detect enteroviral agents in patients with acute stroke can complement existing methods of diagnosis.

  20. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    SHIH-MIN eWANG

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE is a fatal complication of EV71 infection. Among inotropic agents, milrinone is selected as a therapeutic agent for EV71- induced PE due to its immunopathogenesis. Milrinone is a type III phosphodiesterase inhibitor that has both inotropic and vasodilator effects. Its clinical efficacy has been shown by modulating inflammation, reducing sympathetic over-activity, and improving survival in patients with EV71-associated PE. Milrinone exhibits immunoregulatory and anti-inflammatory effects in the management of systemic inflammatory responses in severe EV71 infection.

  1. Development of a multiplex polymerase chain reaction assay for simultaneous identification of human enterovirus 71 and coxsackievirus A16

    OpenAIRE

    Thao, Nguyen Thi Thanh; Ngoc, Nguyen Thi Kim; Tú, Phan Văn; Thúy, Trần Thi; Cardosa, Mary Jane; McMinn, Peter Charles; Phuektes, Patchara

    2010-01-01

    Human enterovirus 71 (HEV71) and coxsackievirus A16 (CVA16) are two major aetiological agents of hand, foot and mouth disease (HFMD) in children. Recently there have been several large outbreaks of HFMD in Vietnam and the Asia-Pacific region. In this study, a multiplex RT-PCR assay was developed in order to detect simultaneously HEV71, CVA16 and other human enteroviruses. Enterovirus detection was performed with a mixture of three pairs of oligonucleotide primers: one pair of published primer...

  2. Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome

    Directory of Open Access Journals (Sweden)

    Hongbin Wang

    2015-07-01

    Full Text Available 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. Conversely, EV71 counteracts inflammasome activation through cleavage of NLRP3 by viral proteases 2A and 3C, which cleave NLRP3 protein at the G493-L494 or Q225-G226 junction, respectively. Moreover, EV71 3C interacts with NLRP3 and inhibits IL-1β secretion when expressed in mammalian cells. These results thus reveal a set of reciprocal regulations between enterovirus 71 and the NLRP3 inflammasome.

  3. Enteroviruses, hygiene and type 1 diabetes: toward a preventive vaccine.

    Science.gov (United States)

    Drescher, Kristen M; von Herrath, Matthias; Tracy, Steven

    2015-01-01

    Enteroviruses and humans have long co-existed. Although recognized in ancient times, poliomyelitis and type 1 diabetes (T1D) were exceptionally rare and not epidemic, due in large part to poor sanitation and personal hygiene which resulted in repeated exposure to fecal-oral transmitted viruses and other infectious agents and viruses and the generation of a broad protective immunity. As a function of a growing acceptance of the benefits of hygienic practices and microbiologically clean(er) water supplies, the likelihood of exposure to diverse infectious agents and viruses declined. The effort to vaccinate against poliomyelitis demonstrated that enteroviral diseases are preventable by vaccination and led to understanding how to successfully attenuate enteroviruses. Type 1 diabetes onset has been convincingly linked to infection by numerous enteroviruses including the group B coxsackieviruses (CVB), while studies of CVB infections in NOD mice have demonstrated not only a clear link between disease onset but an ability to reduce the incidence of T1D as well: CVB infections can suppress naturally occurring autoimmune T1D. We propose here that if we can harness and develop the capacity to use attenuated enteroviral strains to induce regulatory T cell populations in the host through vaccination, then a vaccine could be considered that should function to protect against both autoimmune as well as virus-triggered T1D. Such a vaccine would not only specifically protect from certain enterovirus types but more importantly, also reset the organism's regulatory rheostat making the further development of pathogenic autoimmunity less likely. Copyright © 2014 John Wiley & Sons, Ltd.

  4. 上海市2005~2009年健康儿童肠道病毒携带状况调查%Enterovirus Carrying Status among Healthy Children under 5 Years Old in Shanghai from 2005-2009

    Institute of Scientific and Technical Information of China (English)

    李云逸; 孙晓冬; 丁晓光; 陆菁; 刘敏勇; 李崇山

    2012-01-01

    objective To explore the enterovirus (EV ) carrying status among healthy children under 5 years old in Shanghai from 2005 to 2009. Methods Stool samples were collected from healthy children during peak epidemic seasons for the EV (from July to August). EV was isolated from these stool samples and then was serotyped by neutralization using specific antisera. VP1 code gene of all non-polio EV (NPEV) isolated were sequenced in order to identify serotypes. Results 18 polioviruses were isolated from 1630 stool samples and carrying rate of poliovirus was 1.10%. 227 NPEV were isolated from the 1630 stool samples and carrying rate of NPEV was 13.93% . Poliovirus were identified as vaccine strains by national laboratory of Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention. There was no wild type poliovirus in Shanghai from 2005 to 2009.Coxsackievirus group B type3 (CVB3)isolates from 2005 to 2009 in Shanghai formed two branch, but genetic diversity was found compared with CVB3 isolates from Europe and America. EV Type71 isolates were C4 subgenotype. Conclusion The EVcarrying rate was decline in healthy children in Shanghai from 2005 to 2009 and maintained polio-free status in Shanghai. We still need to establish and improve EV data bank in Shanghai to make futher realizing of the virus and its epidemic situation among healthy population.%目的 了解上海市2005~2009年≤5岁健康儿童肠道病毒(Enterovirus,EV)携带状况.方法 在EV感染的高发季节(6~8月),采集健康儿童粪便标本进行EV分离和血清型鉴定,对分离到的非脊髓灰质炎(Nonpolio) EV( NPEV)测定VP1编码区核苷酸序列以鉴定其血清型.结果 从1630份粪便标本中共分离到18株脊灰病毒( Poliovirus,PV),阳性率为1.10%;分离到227株NPEV,阳性率为13.93%.PV经中国疾病预防控制中心病毒病预防控制所国家脊灰实验室型内鉴定均为疫苗株.上海市2005~2009年无脊

  5. Sentinel surveillance for human enterovirus 71 in Sarawak, Malaysia: lessons from the first 7 years

    Directory of Open Access Journals (Sweden)

    Yao Sik-King

    2006-07-01

    Full Text Available Abstract Background A major outbreak of human enterovirus 71-associated hand, foot and mouth disease in Sarawak in 1997 marked the beginning of a series of outbreaks in the Asia Pacific region. Some of these outbreaks had unusually high numbers of fatalities and this generated much fear and anxiety in the region. Methods We established a sentinel surveillance programme for hand, foot and mouth disease in Sarawak, Malaysia, in March 1998, and the observations of the first 7 years are described here. Virus isolation, serotyping and genotyping were performed on throat, rectal, vesicle and other swabs. Results During this period Sarawak had two outbreaks of human enterovirus 71, in 2000 and 2003. The predominant strains circulating in the outbreaks of 1997, 2000 and 2003 were all from genogroup B, but the strains isolated during each outbreak were genetically distinct from each other. Human enterovirus 71 outbreaks occurred in a cyclical pattern every three years and Coxsackievirus A16 co-circulated with human enterovirus 71. Although vesicles were most likely to yield an isolate, this sample was not generally available from most cases and obtaining throat swabs was thus found to be the most efficient way to obtain virological information. Conclusion Knowledge of the epidemiology of human enterovirus 71 transmission will allow public health personnel to predict when outbreaks might occur and to plan interventions in an effective manner in order to reduce the burden of disease.

  6. Virological Investigation of Enteroviruses From Healthy Children in the Border Areas of Yunnan Province, 2010%2010年云南边境地区健康儿童肠道病毒带毒调查

    Institute of Scientific and Technical Information of China (English)

    黄国斐; 丁峥嵘; 田炳均; 汤晶晶; 张杰; 赵智娴; 陆林

    2012-01-01

    Objective To virological investigate the healthy children under 15 years old who came from the border areas with Myanmar in Yunnan province in 2010. Methods The stool samples of the children aged under 15 years who came from the border areas were collected ( one child collected one stool). Virus isolation and sequencing were conducted for the 400 samples. Results Altogether, 21 non - polio viruses ( NPVs) were detected with an isolation rate of 5.3% (21/400). All the 21 strains were HEV - B viruses, no HEV - A, HEV - C, HEV - D and polioviruses was detected. Conclusion HEV - B viruses were the primary enteroviruses among the healthy children in the border areas with Myanmar in Yunnan province in 2010.%目的 对2010年云南省与缅甸接壤地区15岁以下健康儿童肠道病毒带毒情况进行调查.方法 采集边境地区15岁以下健康儿童的粪便标本(每个儿童1份),对共400份标本进行病毒分离和基因测序定型.结果 400份便标本中检测到非脊灰病毒( non - polio virus,NPV)21株,NPV分离率5.3%.21株病毒全为HEV - B组病毒,未分离到HEV - A、HEV - C、HEV - D组病毒和脊灰病毒.结论 2010年云南省边境地区健康儿童中肠道病毒以B组病毒为主.

  7. DIDS blocks a chloride-dependent current that is mediated by the 2B protein of enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    Shiqi Xie; Kai Wang; Wenjing Yu; Wei Lu; Ke Xu; Jianwei Wang; Bin Ye; Wolfgang Schwarz; Qi Jin2, Bing Sun

    2011-01-01

    Dear Editor, Enterovirus 71 (EV71), which belongs to the genus Enterovirus of the family Picornaviridae, is one of the major pathogens that cause hand, foot and mouth disease, primarily in infants and young children.In recent years, epidemic and sporadic outbreaks of neurovirulent EV71 infections have been reported in many countries and regions, including Japan, China and Taiwan [ 1 ].However,there is still no effective antiviral treatment against severe EV71 infections, and no vaccine is available.

  8. Squamous epitheliotropism of Enterovirus A71 in human epidermis and oral mucosa

    Science.gov (United States)

    Phyu, Win Kyaw; Ong, Kien Chai; Kong, Chee Kwan; Alizan, Abdul Khalil; Ramanujam, Tindivanam Muthurangam; Wong, Kum Thong

    2017-01-01

    Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection. Viral antigens/RNA were associated with cytoplasmic vacuolation and cellular necrosis. Infected primary prepuce epidermal keratinocyte cultures showed cytopathic effects with concomitant detection of viral antigens from 2 days post-infection. Supernatant and/or tissue homogenates from prepuce skin organotypic cultures and primary prepuce keratinocyte cultures showed viral titres consistent with active viral replication. Our data strongly support Enterovirus A71 squamous epitheliotropism in the human epidermis and oral mucosa, and suggest that these organs are important primary and/or secondary viral replication sites that contribute significantly to oral and cutaneous viral shedding resulting in person-to-person transmission, and viraemia, which could lead to neuroinvasion. PMID:28322333

  9. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    R. Poelman (Randy); I. Schuffenecker (Isabelle); C. Van Leer-Buter (Coretta); L. Josset (Laurence); H.G.M. Niesters (Bert); B. Lina (Bruno)

    2015-01-01

    textabstractBackground: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen

  10. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    Poelman, Randy; Schuffenecker, Isabelle; Van Leer-Buter, Coretta; Josset, Laurence; Niesters, Hubert G. M.; Lina, Bruno

    2015-01-01

    Background: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory

  11. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    R. Poelman (Randy); I. Schuffenecker (Isabelle); C. Van Leer-Buter (Coretta); L. Josset (Laurence); H.G.M. Niesters (Bert); B. Lina (Bruno); T. Popow-Kraupp (Therese); S.W. Aberle (Stephan W.); T.K. Fischer (Thea Kølsen); S. Midgley (Sofie); C.B. Christiansen (Claus Bohn); M. Waris (Matti); R. Österback (Riikka); T. Vuorinen (Tytti); C. Savolainen-Kopra (Carita); F. Latronico (Francesca); S. Blomqvist (Soile); N. Ikonen (Niina); M. Lappalainen (Maija); A. Jääskeläinen (Anne); T. Smura (Teemu); L. Pilorge (Léa); M.-C. Legrand-Quillien (Marie-Christine); C. Payan (Christopher); J. Petitjean (Joëlle); A. Vabret (Astrid); M. Ribault (Mélanie); A. Mirand (Audrey); H. Peigue-Lafeuille (Hélène); C. Henquell (Cécile); C. Manoha (Catherine); J.-B. Bour (Jean-Baptiste); M. Darniot (Magali); J. Le Goff (Jérôme); S. Mercier-Delarue (Séverine); C. Scieux (Catherine); S. Pillet (Sylvie); B. Pozzetto (Bruno); Q. Lepiller (Quentin); S. Fafi-Kremer (Samira); F. Stoll-Keller (Françoise); S. Marque-Juillet (Stéphanie); A. Coutard (Aymeric); M. Amara (Marlène); S. Böttcher (Sindy); S. Diedrich (Sabine); A.M. Eis-Hübinger (Anna Maria); S. Aldabbagh (Souhaib); U. Reber (Ulrike); M. Panning; D. Huzly (Daniela); S. Bierbaum (Sibylle); U.G. Liebert (Uwe G.); M. Maier (Melanie); M.J. Carr (Michael J.); G. Tuite (Gráinne); J.A. Guerra (Jorge Abboud); J. O'Gorman (Joanne); C. de Gascun (Cillian); F. Baldanti (Fausto); A. Piralla (Antonio); S. Esposito (Susanna); N. Principi (Nicola); L. Ruggiero (Luca); M. Opp (Matthias); G.A. Donker (Gé); A. Meijer (Adam); H.G.A.M. van der Avoort (Harrie); K. Benschop (Kimberley); M. de Lange (Marit); H.G.M. Niesters (Bert); R. Borger (Renze); L. Scholvinck (Liesbeth); W. van der Reijden (Wil); D. Veenendaal (Dick); E.C.J. Claas (Eric); A.C.T.M. Vossen (Ann C.T.M.); J. Rahamat-Langendoen (Janette); W.J. Melchers (Willem); M.P.G. Koopmans D.V.M. (Marion); A.A. Eijck (Annemiek); S.D. Pas (Suzan); A.-M.B. Kran (Anne-Marte Bakken); K. Bragstad (Karoline); S.G. Dudman (Susanne Gjeruldsen); A. Christensen (Andreas); S. Krokstad (Sidsel); K. Pancer (Katarzyna); E. Abramczuk (Edyta); R. Guiomar (Raquel); P. Pechirra (Pedro); P. Cristovão (Paula); I. Costa (Ines); C. Tecu (Cristina); E. Lupulescu (Emilia); C. Cherciu (Carmen); E. Goldstein (Emily); S. Bennett (Susan); A. Bradley-Stewart (Amanda); K. Gunson (Karen); N. Berginc (Natasa); K. Prosenc (Katarina); M. Campins (Magda); L. Gimferrer (Laura); A. Anton (Andres); F.X. López-Labrador (F. Xavier); L.C. Pérez (Laura Cano); J. Puig-Barberá (Joan); C.G. Cardona (Concepción Gimeno); M.D.O. Mochón (M Dolores Ocete); J. Buesa (Javier); D. Navarro (David); R.O. de Lejarazu Leonardo (R. Ortiz); I.S. Muñoz (Iván Sanz); S. Rojo (Silvia); M. Gozalo-Margüello (Mónica); J.A. Balbín (Jesús Agüero); J. Albert (Jan); A. Samuelson (Agneta); M.R. östlund (Maria Rotzén); R. Dyrdak (Robert); M. Brytting (Mia); E. Hauzenberger (Elenor); K. Zakikhany (Katherina); M. Eriksson (Margareta); C. Moore (Catherine); E. Broberg (Eeva); P. Penttinen (Pasi); E. McCulloch (Elaine); C. Di Lorenzo (Caterina); P. Wallace (Paul); A.M. van Loon (Anton); C. Prifert (Christiane); B. Weißbrich (Benedikt); O. Adams (Ortwin); L. Berlin (Labor); J. Hofmann (Jörg); P. Schnitzler (Paus)

    2015-01-01

    textabstractBackground: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen r

  12. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    R. Poelman (Randy); I. Schuffenecker (Isabelle); C. Van Leer-Buter (Coretta); L. Josset (Laurence); H.G.M. Niesters (Bert); B. Lina (Bruno); T. Popow-Kraupp (Therese); S.W. Aberle (Stephan W.); T.K. Fischer (Thea Kølsen); S. Midgley (Sofie); C.B. Christiansen (Claus Bohn); M. Waris (Matti); R. Österback (Riikka); T. Vuorinen (Tytti); C. Savolainen-Kopra (Carita); F. Latronico (Francesca); S. Blomqvist (Soile); N. Ikonen (Niina); M. Lappalainen (Maija); A. Jääskeläinen (Anne); T. Smura (Teemu); L. Pilorge (Léa); M.-C. Legrand-Quillien (Marie-Christine); C. Payan (Christopher); J. Petitjean (Joëlle); A. Vabret (Astrid); M. Ribault (Mélanie); A. Mirand (Audrey); H. Peigue-Lafeuille (Hélène); C. Henquell (Cécile); C. Manoha (Catherine); J.-B. Bour (Jean-Baptiste); M. Darniot (Magali); J. Le Goff (Jérôme); S. Mercier-Delarue (Séverine); C. Scieux (Catherine); S. Pillet (Sylvie); B. Pozzetto (Bruno); Q. Lepiller (Quentin); S. Fafi-Kremer (Samira); F. Stoll-Keller (Françoise); S. Marque-Juillet (Stéphanie); A. Coutard (Aymeric); M. Amara (Marlène); S. Böttcher (Sindy); S. Diedrich (Sabine); A.M. Eis-Hübinger (Anna Maria); S. Aldabbagh (Souhaib); U. Reber (Ulrike); M. Panning; D. Huzly (Daniela); S. Bierbaum (Sibylle); U.G. Liebert (Uwe G.); M. Maier (Melanie); M.J. Carr (Michael J.); G. Tuite (Gráinne); J.A. Guerra (Jorge Abboud); J. O'Gorman (Joanne); C. de Gascun (Cillian); F. Baldanti (Fausto); A. Piralla (Antonio); S. Esposito (Susanna); N. Principi (Nicola); L. Ruggiero (Luca); M. Opp (Matthias); G.A. Donker (Gé); A. Meijer (Adam); H.G.A.M. van der Avoort (Harrie); K. Benschop (Kimberley); M. de Lange (Marit); H.G.M. Niesters (Bert); R. Borger (Renze); L. Scholvinck (Liesbeth); W. van der Reijden (Wil); D. Veenendaal (Dick); E.C.J. Claas (Eric); A.C.T.M. Vossen (Ann C.T.M.); J. Rahamat-Langendoen (Janette); W.J. Melchers (Willem); M.P.G. Koopmans D.V.M. (Marion); A.A. Eijck (Annemiek); S.D. Pas (Suzan); A.-M.B. Kran (Anne-Marte Bakken); K. Bragstad (Karoline); S.G. Dudman (Susanne Gjeruldsen); A. Christensen (Andreas); S. Krokstad (Sidsel); K. Pancer (Katarzyna); E. Abramczuk (Edyta); R. Guiomar (Raquel); P. Pechirra (Pedro); P. Cristovão (Paula); I. Costa (Ines); C. Tecu (Cristina); E. Lupulescu (Emilia); C. Cherciu (Carmen); E. Goldstein (Emily); S. Bennett (Susan); A. Bradley-Stewart (Amanda); K. Gunson (Karen); N. Berginc (Natasa); K. Prosenc (Katarina); M. Campins (Magda); L. Gimferrer (Laura); A. Anton (Andres); F.X. López-Labrador (F. Xavier); L.C. Pérez (Laura Cano); J. Puig-Barberá (Joan); C.G. Cardona (Concepción Gimeno); M.D.O. Mochón (M Dolores Ocete); J. Buesa (Javier); D. Navarro (David); R.O. de Lejarazu Leonardo (R. Ortiz); I.S. Muñoz (Iván Sanz); S. Rojo (Silvia); M. Gozalo-Margüello (Mónica); J.A. Balbín (Jesús Agüero); J. Albert (Jan); A. Samuelson (Agneta); M.R. östlund (Maria Rotzén); R. Dyrdak (Robert); M. Brytting (Mia); E. Hauzenberger (Elenor); K. Zakikhany (Katherina); M. Eriksson (Margareta); C. Moore (Catherine); E. Broberg (Eeva); P. Penttinen (Pasi); E. McCulloch (Elaine); C. Di Lorenzo (Caterina); P. Wallace (Paul); A.M. van Loon (Anton); C. Prifert (Christiane); B. Weißbrich (Benedikt); O. Adams (Ortwin); L. Berlin (Labor); J. Hofmann (Jörg); P. Schnitzler (Paus)

    2015-01-01

    textabstractBackground: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen r

  13. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    NARCIS (Netherlands)

    Poelman, Randy; Schuffenecker, Isabelle; Van Leer-Buter, Coretta; Josset, Laurence; Niesters, Hubert G. M.; Lina, Bruno

    2015-01-01

    Background: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory s

  14. Neurologic Complications of Enterovirus 71 Infection

    OpenAIRE

    J Gordon Millichap

    1999-01-01

    The neurologic complications associated with the 1998 Taiwan enterovirus 71 epidemic are reported from National Cheng Kung University, Tainan; Chang Gung Children’s Hospital, Kaohsiung; and National Defense Medical Center, Taipei, Taiwan.

  15. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification

    Directory of Open Access Journals (Sweden)

    Alexandr Krasota

    2016-01-01

    Full Text Available Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1% patients compared with 75 (47.2%, 53 (33.3% and 31 (19.5% achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14, E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71 in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

  16. Direct Identification of Enteroviruses in Cerebrospinal Fluid of Patients with Suspected Meningitis by Nested PCR Amplification.

    Science.gov (United States)

    Krasota, Alexandr; Loginovskih, Natalia; Ivanova, Olga; Lipskaya, Galina

    2016-01-06

    Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.

  17. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    Science.gov (United States)

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  18. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    Directory of Open Access Journals (Sweden)

    Win Kyaw Phyu

    Full Text Available Enterovirus A71 (EV-A71 causes self-limiting, hand-foot-and-mouth disease (HFMD that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia, acinar cells (salivary gland, lacrimal gland, lymphoid cells (lymph node, spleen, and muscle fibres (skeletal, cardiac and smooth muscles, liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  19. Outbreak of Enterovirus - 71 Meningitis in Calicut

    Directory of Open Access Journals (Sweden)

    CK Sasidharan

    2016-04-01

    Full Text Available Objective: Enterovirus 71(EV 71 causes wide spectrum of infections ranging from asymptomatic conditions to clinical syndromes like diarrhea, rash, hand-foot-and mouth disease (HFMD, herpangina, aseptic meningitis, encephalitis, myocarditis, acute flaccid paralysis, bulbar and brainstem encephalitis Guillain Barre syndrome, pulmonary haemorrhage. This study deals with an outbreak of aseptic meningitis in children caused by EV 71 virus. Methods: The authors report an outbreak of aseptic meningitis in children in and around Calicut in June 2008. Clinical and laboratory study was done in collaboration with National Centre for Disease Control, New Delhi. 149 children with aseptic meningitis were studied and followed up from June 2008 to May 2009. Result: All children had clinical features suggestive of aseptic meningitis and serology showed the rising antibody titre against EV 71 virus infection. CSF analysis also showed four fold rise in antibodies in one and ≥ 1:2 neutralising antibodies titer against EV- 71 in four samples indicating meningitis due to EV-71. Conclusion: EV 71 was identified as the causative agent of the outbreak of aseptic meningitis in the study and the fact that the EV 71 infection has evolved from minor illness like HFMD to major illness like aseptic meningitis from the same locality is truly alarming.

  20. Replication and Inhibitors of Enteroviruses and Parechoviruses

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden

    2015-08-01

    Full Text Available 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 of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.

  1. Virus load of enterovirus 71 and the severity of hand-foot-mouth disease caused by enterovirus 71%肠道病毒71型病毒载量与手足口病严重程度分析

    Institute of Scientific and Technical Information of China (English)

    邓慧玲; 张瑜; 谢燕; 袁娟; 王军; 王小燕

    2014-01-01

    Objective It's not clear why the severity of hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) was varied clinically.In this study,the relation between the virus load of EV71 and the severity of HFMD was analyzed and the foundation for HFMD control and treatment were laid.Methods Two hundred and fortyseven patients with HFMD caused by EV71 from Jan.2012 to Sep.2013 in Xi'an Children's Hospital were enrolled and clinical data were collected,including age,gender,clinical symptoms,signs,routine blood count,fasting glucose,C-reactive protein and enterovirus.The EV71 virus loads of 247 patients with HFMD were measured by real-time PCR assay.Meanwhile,the effect of EV71 RNA on the severity of HFMD was analyzed.Results In this study,121 mild cases and 126 severe cases with HFMD limb shaking,fasting glucose,lymphocyte and neutrophil percentage were statistically significant between the 2 groups (all P < 0.05).The counts of EV71 RNA from all of the 247 throat swab samples were more than 100 copies/mL,and the highest virus load was 1.1 × 105 copies/mL.The highest value of EV71 RNA was 9.32 × 104 copies/mL and 1.1 × 105 copies/mL in mild and severe cases,respectively,there was no significant difference between the 2 groups (P > 0.05).Conclusions The results of EV71 RNA by RT-PCR are visualized and convenient.The virus loads of EV71 are not associated with the severity of HFMD,but further studies need to analyze.%目的 肠道病毒71型(EV71)感染引起手足口病(HFMD)临床症状轻重不同的病因尚不清楚,通过比较分析EV71 RNA病毒载量与HFMD临床严重程度的关系,为控制及有效治疗HFMD提供临床依据.方法 应用实时荧光定量反转录(RT)-PCR技术检测西安市儿童医院2012年1月至2013年9月随机抽取的247例肛拭子EV71病毒核酸阳性的HFMD住院患儿咽拭子标本中EV71 RNA,同时采集患儿的临床资料,包括年龄、性别、临床症状及体征,血常规、空腹血糖、炎性指

  2. An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice.

    Science.gov (United States)

    In, Hyun Ju; Lim, Heeji; Lee, Jung-Ah; Kim, Hye Jin; Kim, Jin-Won; Hyeon, Ji-Yeon; Yeo, Sang-Gu; Lee, June-Woo; Yoo, Jung Sik; Choi, Young Ki; Lee, Sang-Won

    2017-01-01

    Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.

  3. Epidemiology of Enterovirus D68 in Ontario.

    Directory of Open Access Journals (Sweden)

    Adriana Peci

    Full Text Available In August 2014, children's hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI. In response to CDC reports, Public Health Ontario Laboratories (PHOL launched an investigation of patients being tested for enterovirus D-68 (EV-D68 in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases and those testing negative (controls. EV-D68 was identified in 153/907 (16.8% of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5-9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64. Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.

  4. Epidemiology of Enterovirus D68 in Ontario.

    Science.gov (United States)

    Peci, Adriana; Winter, Anne-Luise; Warshawsky, Bryna; Booth, Tim F; Eshaghi, AliReza; Li, Aimin; Perusini, Stephen; Olsha, Romy; Marchand-Austin, Alex; Kristjanson, Erik; Gubbay, Jonathan B

    2015-01-01

    In August 2014, children's hospitals in Kansas City, Missouri and Chicago, Illinois notified the Centers for Disease Control and Prevention (CDC) about increased numbers of pediatric patients hospitalized with severe respiratory illness (SRI). In response to CDC reports, Public Health Ontario Laboratories (PHOL) launched an investigation of patients being tested for enterovirus D-68 (EV-D68) in Ontario, Canada. The purpose of this investigation was to enhance our understanding of EV-D68 epidemiology and clinical features. Data for this study included specimens submitted for EV-D68 testing at PHOL from September 1, 2014 to October 31, 2014. Comparisons were made between patients who tested positive for the virus (cases) and those testing negative (controls). EV-D68 was identified in 153/907 (16.8%) of patients tested. In the logistic regression model adjusting for age, sex, setting and time to specimen collection, individuals younger than 20 years of age were more likely to be diagnosed with EV-D68 compared to those 20 and over, with peak positivity at ages 5-9 years. Cases were not more likely to be hospitalized than controls. Cases were more likely to be identified in September than October (OR 8.07; 95% CI 5.15 to 12.64). Routine viral culture and multiplex PCR were inadequate methods to identify EV-D68 due to poor sensitivity and inability to differentiate EV-D68 from other enterovirus serotypes or rhinovirus. Testing for EV-D68 in Ontario from July to December, 2014 detected the presence of EV-D68 virus among young children during September-October, 2014, with most cases detected in September. There was no difference in hospitalization status between cases and controls. In order to better understand the epidemiology of this virus, surveillance for EV-D68 should include testing of symptomatic individuals from all treatment settings and patient age groups, with collection and analysis of comprehensive clinical and epidemiological data.

  5. Emergence of enterovirus D68 in Denmark, June 2014 to February 2015

    DEFF Research Database (Denmark)

    Midgley, S E; Christiansen, Claus Bohn; Poulsen, M W;

    2015-01-01

    From June 2014 through February 2015, respiratory samples from 130 Danish patients were screened for enterovirus D68 (EV-D68). Fourteen EV-D68 cases were detected, of which 12 presented with respiratory symptoms, and eight had known underlying disease. The median age of EV-D68 cases was three yea...

  6. Foot-and-mouth disease virus, but not bovine enterovirus, targets the host cell cytoskeleton, via the non-structural protein 3Cpro

    DEFF Research Database (Denmark)

    Armer, Hannah; Moffat, Katy; Wileman, Thomas;

    2008-01-01

    Foot-and-mouth disease virus (FMDV), a member of the Picornaviridae, is a pathogen of cloven-hoofed animals and causes a disease of major economic importance. Picornavirus-infected cells show changes in cell morphology and rearrangement of cytoplasmic membranes, which are a consequence of virus...

  7. MRI findings of enterovirus 71-infected hand, foot and mouth disease complicated with neurological impairment%EV71病毒感染手足口病合并神经系统损害的MRI研究进展

    Institute of Scientific and Technical Information of China (English)

    谢歆昕(综述); 陈旺生; 陈锋; 李建军(审校)

    2016-01-01

    Hand, foot and mouth disease (HFMD) is an infectious disease caused by multiple enterovirus, which mostly happens in preschool children, and is mainly transmitted by routes of digestive tract, respiratory tract and close contact. The major clinical manifestations include fever, rash in mouth and extremities, herpes, and various neuro-logical complications in severe cases, such as encephalitis in brain stem, aseptic meningitis, acute flaccid paralysis (AFP), which result in high morbidity and mortality. Therefore, to diagnose HFMD with neurological complications ear-lier, to establish a treatment plan, and to assess the therapeutic effect are significant for reducing the mortality and mor-bidity. MRI is nowadays an effective method to investigate HFMD with neurological complications. The research prog-ress of MRI regarding HFMD complicated with neurological impairment were reviewed as follows.%手足口病(HFMD)是由多种肠道病毒引起的传染性疾病,好发于学龄前儿童。其主要传播途径为消化道、呼吸道以及密切接触;主要临床表现为发热,口腔和四肢末端的斑丘疹、疱疹,重者可引起多种神经系统并发症,如脑干脑炎、无菌性脑膜炎、急性驰缓性麻痹(AFP)等,致残率和病死率高。因此,早期诊断手足口病并发神经系统损害,制定治疗方案以及治疗效果的评估对降低重症手足口病病死率、致残率具有重要意义,而磁共振(MRI)是目前监测HFMD并发神经系统损害的有效手段。本文就手足口病并神经系统损害的MRI研究进展做一简要综述。

  8. Enterovirus Migration Patterns between France and Tunisia.

    Science.gov (United States)

    Othman, Ines; Mirand, Audrey; Slama, Ichrak; Mastouri, Maha; Peigue-Lafeuille, Hélène; Aouni, Mahjoub; Bailly, Jean-Luc

    2015-01-01

    The enterovirus (EV) types echovirus (E-) 5, E-9, and E-18, and coxsackievirus (CV-) A9 are infrequently reported in human diseases and their epidemiologic features are poorly defined. Virus transmission patterns between countries have been estimated with phylogenetic data derived from the 1D/VP1 and 3CD gene sequences of a sample of 74 strains obtained in France (2000-2012) and Tunisia (2011-2013) and from the publicly available sequences. The EV types (E-5, E-9, and E-18) exhibited a lower worldwide genetic diversity (respective number of genogroups: 4, 5, and 3) in comparison to CV-A9 (n = 10). The phylogenetic trees estimated with both 1D/VP1 and 3CD sequence data showed variations in the number of co-circulating lineages over the last 20 years among the four EV types. Despite the low number of genogroups in E-18, the virus exhibited the highest number of recombinant 3CD lineages (n = 10) versus 4 (E-5) to 8 (E-9). The phylogenies provided evidence of multiple transportation events between France and Tunisia involving E-5, E-9, E-18, and CV-A9 strains. Virus spread events between France and 17 other countries in five continents had high probabilities of occurrence as those between Tunisia and two European countries other than France. All transportation events were supported by BF values > 10. Inferring the source of virus transmission from phylogenetic data may provide insights into the patterns of sporadic and epidemic diseases caused by EVs.

  9. Loss of Virus-Specific Memory T. cells in Coxsackievirus B3 and B4 Infected Mice

    Science.gov (United States)

    There are two major types of enteroviruses: polioviruses and non-polio enteroviruses. While vaccines have effectively eliminated poliovirus infections, no vaccine is currently available for the non-polio enteroviruses. Generation of long-term pathogen specific memory cells is cri...

  10. [Enterovirus nosocomial infections in a neonatal care unit: from diagnosis to evidence, from a clinical observation of a central nervous system infection].

    Science.gov (United States)

    Farcy, C; Mirand, A; Marque Juillet, S; Henquell, C; Neulier, C; Foucaud, P; Peigue-Lafeuille, H

    2012-09-01

    Although enteroviruses generally cause asymptomatic or mild disease, neonates are at higher risk for severe illnesses, among which systemic disease characterized by multiorgan involvement is a potentially fatal condition. Enterovirus neonatal infections may be the source of nosocomial infections in neonatology or in pediatric intensive care units. We report central nervous system infections due to Echovirus 11 in two neonates and the molecular evidence of nosocomial transmission of this strain in a neonatal unit by enterovirus genotyping and phylogenetic analysis. This report illustrates the importance of including enterovirus genome detection in the sepsis screening concomitantly with bacteriological investigations performed at admission of a neonate. Rapid diagnosis and subsequent genotyping could have a beneficial impact on clinical practices at the individual level (reducing the length of antibiotic therapy) and public health policy at the collective level by reinforcing hygiene measures to prevent nosocomial infections, with nurseries and neonatal units being at greater risks.

  11. Clinical and epidemiological peculiarities of enterovirus meningitis in the period of seasonal outbreak in 2015

    Directory of Open Access Journals (Sweden)

    Z. A. Khokhlova

    2016-01-01

    Full Text Available The aim. To analyse the morbidity of the enterovirus infection (EI in Novokuznetsk – the major industrial city of Western Siberia and to determine the clinical peculiarities of enterovirus meningitis (EM in the outbreak period in 2015.The materials and methods. There have been analysed the official statistical data in the period of 2006–2015 and the enterovirus meningitis, clinical manifestations in 148 patients, hospitalized in 2015. Liquor was tested by the method of the polymerase chain reaction (PCR for presence RNA of the enteroviruses. The C-reactive protein value was tested by the method of the latex test and the procalcitonin value was tested by the method of the immunoenzymatic analysis. The statistical material treatment has been done using InStat programme.The results. There has been registered 3,2 times growth of the enterovirus infection morbidity in 2015, compared to 2014, which 6,2 times exceeds Russia, s average rate. The enteroviruses ECHO 30 have been identified in patients, biological material and in wastewater. In the structure of the clinical forms the share of the enterovirus meningitis makes 92, 91%. The children, s morbidity 4,57 times exceeds the total burden of disease. The age structure accompanying the enterovirus meningitis: children 2–6 years of age – 47,3%, 7–14 years of age – 27,7%, 15–17 years of age – 7,43%, 18–53 years of age – 17,57%. Vomiting and headache in children (under the age of 7 are registered rarely, and the full meningeal syndrome and the neutrophil pleocytosis in liquor in children (under the age of 7 are registered more frequently. The rate of children and adults has increased in 2015, compared to 2005. The alteration in clinical picture relates to degree of meningeal syndrome intensity and catarrhal manifestations. The C-reactive protein value (in 67,21% and the procalcitonin value (in 100% don, t exceed the threshold values in patients with

  12. Global emergence of enterovirus D68

    DEFF Research Database (Denmark)

    Holm-Hansen, Charlotte Carina; Midgley, Sofie Elisabeth; Fischer, Thea Kølsen

    2016-01-01

    of unknown cause were reported in several US states and in Europe. Enterovirus D68 infection was confirmed in some of the paralysed children, but not all. Complications in patients who were severely neurologically affected resemble those caused by poliomyelitis. In this paper we systematically review reports...

  13. Inactivation of enteroviruses in sewage with ozone

    Energy Technology Data Exchange (ETDEWEB)

    Ivanova, O.E.; Bogdanov, M.V.; Kazantseva, V.A.; Gabrilevskaia, L.N.; Kodkind, G.K.H.

    The study of ozone inactivation of enteroviruses in sewage showed the presence in sewage of suspensions of organic origin and bacterial flora to influence the rate of inactivation. The inactivation rate of poliomyelitis virus in sewage free from organic suspension and bacterial flora was significantly higher than that in sewage containing such suspension and bacterial flora. The inactivation rate of enteroviruses was found not to depend upon the protein and salt composition and pH of sewage or strain appurtenance of viruses. The inactivation rate of enteroviruses directly depended upon the dose of ozone and time of contact with it. Differences in the resistance of different types of poliomyelitis virus, ECHO and Coxsackie viruses to the effect of ozone are likely exist. These differences are manifested within the range of relatively small doses of ozone. E. coli is more resistant to ozone than entero-viruses. The results of laboratory studies were used to choose the regimen of sanitation of urban sewage to be used in technological cycles of industrial enterprises.

  14. Genetic Diversity of Enterovirus A71, India

    OpenAIRE

    Saxena, Vinay K.; Sane, Sudhir; Nadkarni, Sushma S.; Sharma, Deepa K.; Deshpande, Jagadish M.

    2015-01-01

    We have identified circulation of 3 genogroups of enterovirus (EV) A71 in India. A new genogroup (proposed designation G) was discovered during this study. We isolated genogroups D and G in wide geographic areas but detected subgenogroup C1 only in 1 focus in western India. A systematic nationwide search for EV-A71 is warranted.

  15. [Detection of human enteroviruses with real-time PCR assay using TaqMan fluorescent probe].

    Science.gov (United States)

    Leś, Katarzyna; Przybylski, Maciej; Dzieciatkowski, Tomasz; Młynarczyk, Grazyna

    2010-01-01

    Infections with human enteroviruses are common worldwide and cause a wide range of signs and symptoms. Nowadays in current diagnostics procedures older virological methods, such virus isolation in a cell cultures and seroneutralisation assay, are replaced with molecular biology tests. The aim of the study was development of real-time PCR assay for detection of human adenoviruses. DNA isolated from MK2 cell line infected with nineteen different enterovirus strains was used for development of a qualitative real-time PCR assay using primers targeting a conserved region of the 5'UTR region and a specific TaqMan probe. The analytical sensitivity of real-time PCR assay was tested using serial dilutions of Coxackie A9 cDNA in range between 10 degrees and 10(-8). For comparison typical end-point detected RT-PCR for enterovirus detection with the same cDNA dilutions was made. The sensitivity of novel method was about ten thousand-fold higher than older one. The conclusion is that real-time PCR is very advisable in diagnostics of diseases caused with enteroviruses. The high level of sensitivity, specificity, accuracy, and rapidity provided by this assay are favorable for the use in the detection of enteroviral RNA in clinical specimens, especially from neuroinfections.

  16. Producing infectious enterovirus type 71 in a rapid strategy

    Directory of Open Access Journals (Sweden)

    Qin E-De

    2010-06-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 is an etiologic agent of hand-foot-and-mouth disease (HFMD, and recent HFMD epidemics worldwide have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case-fatality rates. EV71 contains a positive-sense single-stranded genome RNA of approximately 7400 bp in length which encodes a polyprotein with a single open reading frame (ORF, which is flanked by untranslated regions at both the 5' and 3' ends. Results A long distance RT-PCR assay was developed to amplify the full length genome cDNA of EV71 by using specific primes carrying a SP6 promoter. Then the in vitro synthesized RNA transcripts from the RT-PCR amplicons were then transfected into RD cells to produce the rescued virus. The rescued virus was further characterized by RT-PCR and indirect fluorescent-antibody (IFA assay in comparison with the wild type virus. The rescued viruses were infectious on RD cells and neurovirulent when intracerebrally injected into suckling mice. Conclusions Thus, we established a rapid method to produce the infectious full length cDNA of EV71 directly from RNA preparations and specific mutations can be easily engineered into the rescued enterovirus genome by this method.

  17. African Non-Human Primates Host Diverse Enteroviruses

    Science.gov (United States)

    Mombo, Illich Manfred; Lukashev, Alexander N.; Bleicker, Tobias; Brünink, Sebastian; Berthet, Nicolas; Maganga, Gael D.; Durand, Patrick; Arnathau, Céline; Boundenga, Larson; Ngoubangoye, Barthélémy; Boué, Vanina; Liégeois, Florian; Ollomo, Benjamin; Prugnolle, Franck; Drexler, Jan Felix; Drosten, Christian; Renaud, François; Rougeron, Virginie; Leroy, Eric

    2017-01-01

    Enteroviruses (EVs) belong to the family Picornaviridae and are responsible for mild to severe diseases in mammals including humans and non-human primates (NHP). Simian EVs were first discovered in the 1950s in the Old World Monkeys and recently in wild chimpanzee, gorilla and mandrill in Cameroon. In the present study, we screened by PCR EVs in 600 fecal samples of wild apes and monkeys that were collected at four sites in Gabon. A total of 32 samples were positive for EVs (25 from mandrills, 7 from chimpanzees, none from gorillas). The phylogenetic analysis of VP1 and VP2 genes showed that EVs identified in chimpanzees were members of two human EV species, EV-A and EV-B, and those identified in mandrills were members of the human species EV-B and the simian species EV-J. The identification of two novel enterovirus types, EV-B112 in a chimpanzee and EV-B113 in a mandrill, suggests these NHPs could be potential sources of new EV types. The identification of EV-B107 and EV90 that were previously found in humans indicates cross-species transfers. Also the identification of chimpanzee-derived EV110 in a mandrill demonstrated a wide host range of this EV. Further research of EVs in NHPs would help understanding emergence of new types or variants, and evaluating the real risk of cross-species transmission for humans as well for NHPs populations. PMID:28081564

  18. Epidemics of enterovirus infection in Chungnam Korea, 2008 and 2009

    Directory of Open Access Journals (Sweden)

    Hwang SeoYeon

    2011-06-01

    Full Text Available Abstract Previously, we explored the epidemic pattern and molecular characterization of enteroviruses isolated in Chungnam, Korea from 2005 to 2006. The present study extended these observations to 2008 and 2009. In this study, enteroviruses showed similar seasonal prevalent pattern from summer to fall and age distribution to previous investigation. The most prevalent month was July: 42.9% in 2008 and 31.9% in 2009. The highest rate of enterovirus-positive samples occurred in children

  19. 病原型别对手足口病患儿发病至确诊间隔时间的影响分析%The Influkence of Enterovirus Serotype on the Duration from Onset to Diagnosis of Children with Hand, Foot, and Mouth disease

    Institute of Scientific and Technical Information of China (English)

    陶建平; 梁会营; 徐翼; 孙新

    2015-01-01

    目的:估测不同病原型别手足口病患儿发病至确诊间隔时间并探讨其对间隔时间的影响。方法:选取2010年1月-2014年12月期间经广州市妇女儿童医疗中心实验室确诊的1367例手足口病患儿为研究对象;采用非参数Kruskal-Wallis H检验和Logistic回归分析病原型别对间隔时间的影响。结果:不同病原型别手足口病患儿间隔时间呈正偏态分布,中位数为2.38天(四分位数:1.38-2.83),且从“CV-A16(1.79天)→EV71(2.38天)→其它型别(2.45天)”逐渐延长(P<0.001)。多因素回归分析结果显示:与CV-A16型别相比,EV71型别(OR=1.46,95%CI:1.05-2.02)和其它型别(OR=1.92,95%CI:1.52-2.44)可显著增加间隔时间>2天的风险。结论:绝大多数手足口病患儿无法在当天得到实验室确诊,需要进一步提高实验室确诊能力和病原型别鉴定能力。%Objective:To study the duration from onset to diagnosis of hand, foot, and mouth disease (HFMD) and the influence of enterovirus serotype on it. Methods:A total of 1367 laboratory confirmed HFMD pediatric patients in Guangzhou Women and Children Medical Center and agreed to participate in our study were recruited from January 2010 to December 2014. Descriptive analysis was performed for the time interval while Kruskal-Wallis H tests and Logistic regression analysis were used to study the influence of enterovirus serotype on the interval. Results: Onset-diagnosis interval appeared positively skewed with distribution at median of 2.38 days (Interquartile range: 1.38-2.83). Furthermore, the interval was significantly extended from 1.79 days for Coxsackie virus A16 (CV-A16) to 2.38 days for Enterovirus 71 (EV 71) and 2.45 days for other enterovirus (P<0.001). Compared with patients with CV-A16, the patients with EV 71 and others had significantly increased risks of more than 2-day delays in

  20. MRI findings of neurologic complications in the enterovirus 71-infected hand-foot-mouth disease%肠道病毒71型感染手足口病合并神经系统损害的MRI表现

    Institute of Scientific and Technical Information of China (English)

    陈峰; 李建军; 刘涛; 向伟; 文国强

    2010-01-01

    Objective To explore the imaging characteristics of neurologic complications associated with the enterovirus 71 ( EV71 ) epidemic by analyzing 25 cases and reviewing the literature. Methods Twenty-five cases of hand-foot-mouth disease with neurologic complications during the recent EV71 outbreaks of Hainan province were studied for the clinical features and imaging findings, and literature were reviewed.Results In 5 cases, acute flaccid paralysis associated with EV71-infected hand-foot-mouth disease was related to the linear high signal in the spinal cord on sagittal images. Two cases showed symmetrical, welldefined hyperintense lesions in the spinal cord on T2WI transverse. Strong enhancement of the ventral horns and root was seen on the contrast-enhanced axial T1WI. In brainstem encephalitis, all lesions presented with significant hyperintensity on T2WI and hypointense on T1WI in the posterior portions of the medulla oblongata, midbrain, and pons. The manifestations of aseptic meningitis (AM) on MRI have no characteristics, but subdural effusion, meningeal enhancement and hydrocephalus can be the indirect signs of AM. Conclusions MRI is an effective method to investigate neurologic complications associated with the EV71 epidemic. Posterior portions of the medulla oblongata and pons, bilateral ventral horns of spinal involvement are characteristic findings of enteroviral encephalomyelitis.%目的 探讨肠道病毒71型(EV71)感染手足口病(HFMD)合并神经系统损害的MRI表现及特征.方法 回顾性分析海南省EV71感染流行期间25例伴有神经系统损害HFMD患儿临床、MRI表现,并结合文献分析其可能机制.结果 HFMD合并急性弛缓性麻痹(AFP)5例,典型MRI表现为矢状面脊髓内长条形长T1、长T2信号,横断面显示相应节段脊髓前角点状长T2信号,增强扫描部分前角、脊神经前根明显强化.HFMD合并脑干脑炎15例,MRI横断面显示桥脑、延髓、中脑后部长T1、长T2

  1. Chebulagic Acid, a Hydrolyzable Tannin, Exhibited Antiviral Activity in Vitro and in Vivo against Human Enterovirus 71

    Directory of Open Access Journals (Sweden)

    Lianfeng Zhang

    2013-05-01

    Full Text Available Human enterovirus 71 is one of the major causative agents of hand, foot and mouth disease in children under six years of age. Presently, no vaccines or antiviral drugs have been clinically available to employ against EV71. In this study, we demonstrate that treatment with chebulagic acid reduced the viral cytopathic effect on rhabdomyosarcoma cells with an IC50 of 12.5 μg/mL. The utilization of the chebulagic acid treatment on mice challenged with a lethal dose of enterovirus 71 was able to efficiently reduce mortality and relieve clinical symptoms through the inhibition of viral replication. Chebulagic acid may represent a potential therapeutic agent to control infections to enterovirus 71.

  2. 手足口病患者家庭密切接触者肠道病毒感染及环境污染状况调查%Study on enterovirus infection in family close contacts of patients with hand, foot and mouth disease and the contamination of environment

    Institute of Scientific and Technical Information of China (English)

    孙立梅; 林锦炎; 曾汉日; 康敏; 郑焕英; 邓爱萍; 何剑峰; 柯昌文; 张永慧

    2012-01-01

    Objective To understand the enterovirus infection in family close contacts of patients with hand,foot and mouth disease (HFMD) and the contamination of environment.Methods Forty-one HFMD cases confirmed by laboratory from web-based surveillance system during July to August 2010 in Guangdong Province were selected.All members of the cases′ family were investigated by collecting their information on demography,habit of domestic hygiene and hygiene status in household.The stool samples of all members and the smear samples from the surface of family belongings from 16 families were collected and the enterovirus was detected by real time quantitative polymerase chain reaction.The data were analyzed by chi square teat and t test.Results Forty-one HFMD cases′ families and 135 close contacts were included in this survey.The infection rate of the enterovirus was 39.2% (53/135) in all close contacts.Of all the investigated families,the infectionrate was 58.5% (24/41) in family with one or more close contacts and 9.8% (4/41) in family with all close contacts.The differences of infection rates of enterovirus among the members of parents (32.5%,25/77),grandparents/aunts/ uncles (43.3%,13/30) and cousins (53.6%,15/28) didn′t show statistical significance (χ2 =4.07,P=0.131).The infection rate of enterovirus in close contacts from family with more than 5 members was higher than that from family with 4 or less members (OR=1.4,95%CI 1.1-1.9).Among 135 close contacts,27.4% (37/135) were infected with the same types of entervirus as that of HFMD case in the family and 11.9% (16/135) were infected with the different virus types.In 33 family belongings samples from 16 families,the positive rate of enterovirus detection was 6.1% (2/33).Between 17 families with enterovirus testing negative and 23 families with enterovirus testing positive in close contacts,there were no statistical differences of the family hygiene status,hand-washing of babysitter

  3. Evolution of re-emergent virus and its impact on enterovirus 71 epidemics.

    Science.gov (United States)

    Huang, Sheng-Wen; Kiang, David; Smith, Derek J; Wang, Jen-Ren

    2011-08-01

    Enterovirus 71 (EV71), a member of the Enterovirus genus in the Picornaviridae family, has become an emergent infectious disease worldwide, most notably in Asia. As a neurotropic virus, EV71 infection occasionally causes neurological diseases with pulmonary edema, which is fatal for children. In this review, we examine the epidemiology of EV71, with three waves of increased EV71 activity since the 1970s and discuss the genotypic changes in phylogeny between the outbreaks or epidemics. Genetic changes including mutations and recombinations as well as the diversity of antigenic properties among EV71 strains in various outbreaks are described. Furthermore, the impact of genetic changes on viral pathogenesis and vaccine candidate selection are addressed. In conclusion, these genetic and antigenic investigations of EV71 evolution have provided us with new insight into the trend of EV71 epidemiology, which may contribute to a better understanding of the viral pathogenesis and vaccine development.

  4. Reproducibility of AMPLICOR enterovirus PCR test results.

    OpenAIRE

    1997-01-01

    The reproducibility of AMPLICOR enterovirus PCR test results was determined with clinical samples of cerebrospinal fluid, serum, urine, and throat and rectal swabs. Among 608 samples from which duplicate aliquots were run simultaneously, only seven pairs gave discordant results. Among 104 samples from which duplicate aliquots were run in separate assays, no discordance was seen. Overall, the reproducibility of test kit results was 99% (705 of 712).

  5. First isolation of enterovirus 71 (EV-71 from Northern Brazil

    Directory of Open Access Journals (Sweden)

    Lamarão Leticia Martins

    2003-01-01

    Full Text Available Enterovirus 71 (EV-71 has been associated to cases of neurological disease in many countries including Brazil. This virus has now been reported from three of the five Brazilian regions. Our study relates the findings concerning to the first isolate of this virus in Northern region of Brazil. A 15-month old female patient, from the rural zone of the municipality of Santana do Araguaia in southern Pará state was admitted at the hospital with acute, flaccid, asymmetric and ascending motor deficiency, located in the right lower limb. Stools samples from this child were inoculated in RD cells and was isolated an EV-71. We plan to sequence our strain and compare it to other isolates in Brazil. Differences at the molecular level can explain why EV-71 strains circulating in other continents, such as Asia, appear to be more virulent.

  6. [Contamination of protozoa by enteroviruses in fresh water and sewages].

    Science.gov (United States)

    Skachkov, M V; Al'misheva, A Sh; Plotnikov, A O; Nemtseva, N V; Skvortsov, V O

    2009-01-01

    To determine rate of infection of protozoa by enteroviruses to assess the potential role of protozoa as a natural reservoir of enteroviruses. The samples were collected from flowing and stagnant water reservoirs in Orenburg region in summer and autumn. The samples of sewages were taken in all stages of their treatment. Cultures of protozoa were isolated with micromanipulator equipped with micropipette, incubated on Pratt's medium at 25 degrees C and fed with Pseudomonas fluorescens culture. RNA of enteroviruses was detected by reverse transcription polymerase chain reaction (RT-PCR). Seventy-two protozoan species were found in Ural river, whereas 15 and 38 species were found in lakes and sewages respectively. Enteroviruses were detected by RT-PCR in 61.8% cultures of protozoa belonging to 23 species of flagellates, amoebae and ciliates isolated from natural water bodies undergoing anthropogenic impact as well as from sewages in all stages of their treatment. Predominant localization of enteroviruses in dominant taxons of protozoa (Paraphysomonas sp., Spumella sp., Petalomonas poosilla, Amoeba sp.) was noted. Obtained data confirm presence of enteroviruses in protozoa living both in flowing and stagnant recreation natural water bodies as well as in sewages and confirm the hypothesis of persistence of enteroviruses in protozoa and the reservoir role of the latter. Contingency of life cycles of viruses and protozoa allows to explain the seasonality of aseptic meningitis incidence caused by enteroviruses, which peaks in summer and autumn when protozoa massively multiply in water bodies.

  7. Possible Tick-Borne Human Enterovirus Resulting in Aseptic Meningitis

    OpenAIRE

    Freundt, Eric C.; Beatty, Douglas C.; Stegall-Faulk, Teresa; Wright, Stephen M.

    2005-01-01

    Enterovirus-specific genetic sequences were isolated from two Amblyomma americanum tick pools. Identical genetic sequences were later obtained from cerebrospinal fluid of a patient with aseptic meningitis and a recent history of tick attachment. These observations suggest the possibility of an emerging tick-borne human enterovirus associated with aseptic meningitis.

  8. Enterovirus and parechovirus infection in children : a brief overview

    NARCIS (Netherlands)

    de Crom, S. C. M.; Rossen, J. W. A.; van Furth, A. M.; Obihara, C. C.

    2016-01-01

    Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of

  9. isolation of enterovirus from feacal samples of patients with diabetes ...

    African Journals Online (AJOL)

    boaz

    cause beta cell damage and diabetes mellitus has become more and more relevant when recent studies have provided new ... can occur at any age but is most frequently ... syndromes associated with enteroviruses include ... CV-B and other enterovirus serotypes can ... activation of autoimmune effector cells against.

  10. Enterovirus and parechovirus infection in children : a brief overview

    NARCIS (Netherlands)

    de Crom, S. C. M.; Rossen, J. W. A.; van Furth, A. M.; Obihara, C. C.

    2016-01-01

    Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of

  11. Acute Flaccid Paralysis Associated with Novel Enterovirus C105.

    Science.gov (United States)

    Horner, Liana M; Poulter, Melinda D; Brenton, J Nicholas; Turner, Ronald B

    2015-10-01

    An outbreak of acute flaccid paralysis among children in the United States during summer 2014 was tentatively associated with enterovirus D68 infection. This syndrome in a child in fall 2014 was associated with enterovirus C105 infection. The presence of this virus strain in North America may pose a diagnostic challenge.

  12. Enterovirus and parechovirus infection in children : a brief overview

    NARCIS (Netherlands)

    de Crom, S. C. M.; Rossen, J. W. A.; van Furth, A. M.; Obihara, C. C.

    Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of

  13. Perception of the Risks of Ebola, Enterovirus-E68 and Influenza Among Emergency Department Patients

    Directory of Open Access Journals (Sweden)

    Lauren K. Whiteside

    2016-06-01

    Full Text Available Introduction: Emerging infectious diseases often create concern and fear among the public. Ebola virus disease (EVD and enterovirus (EV-68 are uncommon viral illnesses compared to influenza. The objective of this study was to determine risk for these viral diseases and then determine how public perception of influenza severity and risk of infection relate to more publicized but less common emerging infectious diseases such as EVD and EV-68 among a sample of adults seeking care at an emergency department (ED in the United States. Methods: We included consenting adults who sought care in two different urban EDs in Seattle, WA in November 2014. Excluded were those who were not fluent in English, in police custody, had decreased level of consciousness, a psychiatric emergency, or required active resuscitation. Patients were approached to participate in an anonymous survey performed on a tablet computer. Information sought included demographics, medical comorbidities, risk factors for EVD and EV-68, and perceptions of disease likelihood, severity and worry for developing EVD, EV-68 or influenza along with subjective estimates of the number of people who have died of each virus over the year in the United States. Results: A total of 262 (88.5% participation rate patients participated in the survey. Overall, participants identified that they were more likely to get influenza compared to EVD (p<0.001 or EV-68 (p<0.001, but endorsed worry and concern about getting both EVD and EV-68 despite having little or no risk for these viral diseases. Nearly two-thirds (64% of participants had at-least one risk factor for an influenza-related complication. Most participants (64% believed they could get influenza in the next 12 months. Only 52% had received a seasonal influenza vaccine. Conclusion: Perception of risk for EVD, EV-68 and influenza is discordant with actual risk as well as self-reported use of preventive care. Influenza is a serious public health

  14. Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone.

    Directory of Open Access Journals (Sweden)

    Hongjie Xia

    2015-07-01

    Full Text Available 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 includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71, which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3'-to-5' unwinds RNA helices in an adenosine triphosphate (ATP-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16, another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings

  15. Somatic coliphages as surrogates for enteroviruses in sludge hygienization treatments.

    Science.gov (United States)

    Martín-Díaz, Julia; Casas-Mangas, Raquel; García-Aljaro, Cristina; Blanch, Anicet R; Lucena, Francisco

    2016-01-01

    Conventional bacterial indicators present serious drawbacks giving information about viral pathogens persistence during sludge hygienization treatments. This calls for the search of alternative viral indicators. Somatic coliphages' (SOMCPH) ability for acting as surrogates for enteroviruses was assessed in 47 sludge samples subjected to novel treatment processes. SOMCPH, infectious enteroviruses and genome copies of enteroviruses were monitored. Only one of these groups, the bacteriophages, was present in the sludge at concentrations that allowed the evaluation of treatment's performance. An indicator/pathogen relationship of 4 log10 (PFU/g dw) was found between SOMCPH and infective enteroviruses and their detection accuracy was assessed. The obtained results and the existence of rapid and standardized methods encourage the inclusion of SOMCPH quantification in future sludge directives. In addition, an existing real-time quantitative polymerase chain reaction (RT-qPCR) for enteroviruses was adapted and applied.

  16. Innate Immunity Evasion by Enteroviruses: Insights into Virus-Host Interaction

    Directory of Open Access Journals (Sweden)

    Xiaobo Lei

    2016-01-01

    Full Text Available Enterovirus genus includes multiple important human pathogens, such as poliovirus, coxsackievirus, enterovirus (EV A71, EV-D68 and rhinovirus. Infection with EVs can cause numerous clinical conditions including poliomyelitis, meningitis and encephalitis, hand-foot-and-mouth disease, acute flaccid paralysis, diarrhea, myocarditis and respiratory illness. EVs, which are positive-sense single-stranded RNA viruses, trigger activation of the host antiviral innate immune responses through pathogen recognition receptors such as retinoic acid-inducible gene (RIG-I-likeand Toll-like receptors. In turn, EVs have developed sophisticated strategies to evade host antiviral responses. In this review, we discuss the interplay between the host innate immune responses and EV infection, with a primary focus on host immune detection and protection against EV infection and viral strategies to evade these antiviral immune responses.

  17. Construction and characterization of infectious cDNA clones of enterovirus 71(EV71)

    Institute of Scientific and Technical Information of China (English)

    Ying-wei; Ma; Shu-bin; Hao; Le-le; Sun; Jing; Li; Qiao; Qiao; Feng; Gao; Li; Zhao; Xue-jie; Yu; Zhi-yu; Wang; Hong-ling; Wen

    2015-01-01

    Dear Editor,Enterovirus 71(EV71),a member of the genus Enterovirus of the family Picornaviridae,is a single-stranded,positive-sense RNA virus that usually causes mild handfoot-mouth disease(HFMD)in children,with symptoms such as fever,diarrhea,and herpangina(Liu et al.,2013).However,certain strains of EV71 infection can cause severe neurological complications,such as SDLY107(Sun et al.,2014).EV71 is classified into three distinct genotypes(A–C);the B and C genotypes are further divided into B1–B5 and C1–C5 genotypes,respectively,based on

  18. 肠道病毒71型和柯萨奇病毒A组16型感染的手足口病患儿的相关特征对比研究%Comparisons of epidemiological and clinical characteristics in children with hand-foot-mouth disease caused by Enterovirus 71 and Coxackievirus A16

    Institute of Scientific and Technical Information of China (English)

    贾蕾; 赵成松; 张莉; 李爽; 张代涛; 刘白薇; 王全意; 黎新宇

    2011-01-01

    Objective To compare the differences of epidemiological and clinical characteristics in children with hand-foot-mouth disease (HFMD) caused by Coxsackievirus A16 (CA16) and Enterovirus 71 ( EV71 ). Methods The samples of vesicle fluid and throat swabs of 108 children with HFMD were collected and detected for enterovirus by RTPCR. The clinical data of children with EV71 and CA16 infection were retrospectively reviewed and compared. Results The total positive rate of enterovirus was 97.2% ( 105/108 ). Of the 105 cases, 56 cases were positive for EV71 (51.9%), 39 cases were positive for CA16 (36.1% ), 2 cases were positive for other enterovirus ( 1.9% ), and 8 cases were co-infected by EV71 and CA16 (7.4%). There were no significant differences in age and sex between EV71 and CV16 infected cases. The univariate analysis showed that the incidences of herpes of mouth, erythra of knees, and nose running in children infected by CA16 were higher than in those infected by EV71. The multivariate logistic regression analysis showed that the HFMD children who had erythra of knees had higher probability of CA16 infection. Conclusions EV71 should be considered as the pathogen in children with HFMD who have no herpes of mouth, erythra of knees, and nose running.%目的 比较由肠道病毒71型(EV71)和柯萨奇病毒A组16型(CA16)感染的手足口病(HFMD)患儿流行病学情况及临床特征的差异.方法 采集108名临床诊断HFMD患儿疱疹液和咽拭子标本,使用RT-PCR进行肠道病毒检测,对EV71和CA16感染患儿的临床资料进行回顾性分析并比较.结果 108名患儿的肠道病毒总阳性率为97.2%(105/108),其中EV71、CA16、其他肠道病毒及EV71和CA16混合感染分别占51.9%(56/108),36.1%(39/108),1.9%(2/108),7.4%(8/108).EV71感染患儿和CA16感染患儿两组间年龄、性别差异无统计学意义.单因素分析显示,CA16感染患儿口腔疱疹、膝部皮疹、流涕的发生比率高于EV71感染患儿.进一步

  19. Molecular epidemiology of human enterovirus associated with aseptic meningitis in Shandong Province, China, 2006-2012.

    Directory of Open Access Journals (Sweden)

    Zexin Tao

    Full Text Available BACKGROUND: Human enteroviruses (HEVs are common causes of acute meningitis. However, there is limited information about HEV associated with aseptic meningitis in mainland China because it has not been classified as a notifiable disease. OBJECTIVES: To characterize the HEVs associated with sporadic aseptic meningitis in China and to analyze their genetic features. STUDY DESIGN: Cerebrospinal fluid, throat swab and feces specimens were collected from patients with aseptic meningitis in 5 sentinel hospitals in Shandong Province, China between 2006 and 2012. Virological investigation (viral isolation and molecular identification and phylogenetic analysis were performed. RESULTS: A total of 437 hospitalized patients were reported, and enteroviruses were detected in the specimens from 84 patients (19.2% and were identified into 17 serotypes. The nine main serotypes were echovirus (E 30 (27.4%, EV71 (13.1%, coxsackievirus (CV B1 (9.5%, CVB3 (7.1%, CVB5 (7.1%, E6 (7.1%, E9 (7.1%, CVA9 (6.0%, and CVA10 (3.6%. Monthly distribution of isolated enteroviruses revealed a major peak in summer-fall season and a small second peak in winter constituted totally by EV71. Sequence analysis on VP1 coding region suggested Shandong strains had great genetic divergence with isolates from other countries. CONCLUSIONS: Multiple serotypes were responsible for enterovirus meningitis in mainland China. Aseptic meningitis caused by EV71 and coxsackie A viruses-the predominant pathogens for the hand, foot, and mouth disease-is currently an important concern in mainland China.

  20. 肠道病毒71型手足口病121例临床分析%Clinical analysis of 121 cases of hand-foot-mouth disease caused by enterovirus 71 infection.

    Institute of Scientific and Technical Information of China (English)

    陆海燕; 孙宝昌; 赵钱雷; 陈旺强; 杨祖钦; 周朱瑛; 林忠东; 陈益平

    2011-01-01

    Objective To study the clinical features of hand-foot-mouth disease (HFMD) caused by enterovirus 71 (EV71) infection. Methods Clinical data of hospitalized children with hand-foot-mouth disease caused by EV71 infection from May 2010 to August 2010 were analyzed retrospectively. The difference of clinical manifestation and results of auxiliary examination between intensive HFMD group and serious HFMDgroup were compared. Results High fever and nontypical skin rash showed significant difference between intensive group and serious group(P = 0.002,P = 0.000, respectively) ; 120 EV71-positived HFMD cases (99.17%) showed neurological impairments. The major neurological features included fatigue (84.30% ) , frequent vomiting (65.30% ) , limb tremble (60.33% ) and sleep disorders (53.72%). The rate of abnormal knee reflex was 52.07% in physical examination. The incidence of vomiting(P = 0.001), unconsciousness {P = 0.000) .abnormal muscular tension(P = 0.000) .abnormal heart rate (P = 0.000),dysarteriotony (P = 0.000) , capillary refill time being more than 3 seconds (CRT > 3 s) (P = 0.000) , tachypnea or dyspnea (P = 0.000) and pulmonary exudative lesion in chest X-ray (P = 0.000) was more frequent in serious group compared with intensive group,There were 51 cases (42.15% ) with a peripheral blood WBC count of more than 12 x 10YL or less than 4 x 107L.52 cases (42.98% ) with blood glucose level of more than 6 mmol/L and cardiac troponin I elevated in 22 cases (18.18% ). The above three indexes were significantly different between two groups (P 3s,tachypnea or dyspnea, and pulmonary exudative lesion are risk factors of serious HFMD. Early identification and correct treatment are the key to the rescue of serious HFMD.%目的 分析肠道病毒71型(EV71)感染所致手足口病的临床特征.方法 回顾性分析2010 -05- 01-2010-08-31日温州医学院附属育英儿童医院121例EV71感染所致手足口病的住院患儿病例资料.比较重型组和危重型组的

  1. Download this PDF file

    African Journals Online (AJOL)

    abp

    2012-07-16

    Jul 16, 2012 ... Human Enteroviruses isolated during acute flaccid paralysis surveillance in Ghana: ... Three children from whom non-polio enteroviruses were isolated had residual paralysis while one child with ..... Grist, NR and EJ Bell.

  2. Clinical and MRI Features of Hand - foot - mouth Disease Related to Enterovirus 71 and Associated with Acute Flaccid Paralysis%合并急性弛缓性瘫痪的肠道病毒71型相关手足口病临床及MRI特征研究

    Institute of Scientific and Technical Information of China (English)

    叶信健; 刘锟; 张桂艳; 白光辉; 周云新; 严志汉

    2012-01-01

    Objective To investigate the clinical and MRI characteristics of hand - foot - mouth diseases related to enlerovinis 71 ( EV71) combined with acute flaccid paralysis ( AFP) . Methods Hie clinical and MRI manifestations of fourteen infants suffered from hand - foot - mouth diseases related to enterovirus 71 (EV7I) combined with AFP were retrospectively analyzed. Results Among the fourteen infants with AFP, one had paralysis of unilateral upper limbs, one had paralysis of the unilateral lower limbs, two had paralysis of bilateral upper limbs, one had paralysis of bilateral lower limbs, three had hemiplegia, and six had quadriplegia. All cases clinically presented acute limb myaslhenia with tendon reflex and muscular tension lowered. On the spinal MRI, the lesions involved the anterior hom regions of spinal cord had hyperintensity on T2 - weighted images and hypointensity on T1 - weighted images, which were elongated on sagittal images and patchy on transverse images. Six patients simultaneously contained brainstem encephalitis. MRI showed that the lesions located at the posterior portions of the medulla, pons. The lesions had hyperintensity on T2 -weighted images and hypointensity on T1 - weighted images. Conclusion MRI is the most effective method on evaluating the range, degree and prognosis of the injuries on spinal cord and brain of hand - foot - mouth diseases related to enterovirus 71 ( EV71) combined with AFP. MRI findings have relative specificity. The hand - foot - mouth diseases related to enterovirus 71 (EV71) combined with AFP often involve the anterior horn of the spinal cord, medulla oblongata and pons.%目的 探讨合并急性弛缓性瘫痪(AFP)的肠道病毒71型(EV71)相关手足口病(HFMD)的临床及MRI特征.方法 回顾性分析14例伴有AFP的EV71型相关HFMD患儿临床及MRI资料,并总结其临床及MRI特征.结果 14例患儿中,单上肢瘫痪1例、单下肢瘫痪1例、双上肢瘫痪2例、双下肢瘫痪1例、单侧偏瘫3

  3. Quinacrine impairs enterovirus 71 RNA replication by preventing binding of polypyrimidine-tract binding protein with internal ribosome entry sites.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Since the 1980s, epidemics of enterovirus 71 (EV71 and other enteroviruses have occurred in Asian countries and regions, causing a wide range of human diseases. No effective therapy is available for the treatment of these infections. Internal ribosome entry sites (IRESs are indispensable for the initiation of translation in enteroviruses. Several cellular factors, as well as the ribosome, are recruited to the conserved IRES during this process. Quinacrine intercalates into the RNA architecture and inhibits RNA transcription and protein synthesis, and a recent study showed that quinacrine inhibited encephalomyocarditis virus and poliovirus IRES-mediated translation in vitro without disrupting internal cellular IRES. Here, we report that quinacrine was highly active against EV71, protecting cells from EV71 infection. Replication of viral RNA, expression of viral capsid protein, and production of virus were all strongly inhibited by quinacrine. Interaction of the polypyrimidine tract-binding protein (PTB with the conserved IRES was prevented by quinacrine. Coxsackieviruses and echovirus were also inhibited by quinacrine in cultured cells. These results indicate that quinacrine may serve as a potential protective agent for use in the treatment of patients with chronic enterovirus infection.

  4. Enteroviruses as a possible cause of hypertension, dilated cardiomyopathy (DCM) and hypertensive heart failure (HHF) in South western Nigeria.

    Science.gov (United States)

    Okonko, I O; Adebiyi, A A; Ogah, O S; Adu, F D

    2013-12-01

    Human enteroviruses have long been associated with various diseases of man resulting into a wide range of acute symptoms involving the cardiac and skeletal muscles, central nervous system, pancreas, skin and mucous membranes. To assess the role of enteroviruses in the etiology of hypertension, DCM and HHF. We obtained stool specimens from 70 subjects comprising 65 patients and 5 controls and isolation was carried out on RD, L20B, HEp-2C and Vero cell lines and identified by neutralization with standard antisera (RIVM). Thirty-six enteroviruses were isolated and identified to be Coxsackieviruses-B5, A9, Echoviruses 1, 6, 7, 9, 11, 12, 22, 30 and Poliovirus type 1 and 3. Three most frequently occurring enterovirus serotypes which constitute 60.0% of the 30 NPEV typed and 50.0% of all the isolates were Echoviruses, Coxsackie-B5-virus and Coxsackievirus-A9. Echoviruses constituted 50.0% of all the serotypes while Coxsackieviruses-B5 and A9 accounts for the 27.8 % and 5.6% respectively. Enteroviral isolation rate was higher in age groups 51 years and above. The percentage of study subjects who had Coxsackie-B5-viruses and echoviruses was significantly (PCoxackie-B5-virus, Echovirus-6 and Echovirus-11 were found in both study locations. The findings of this study showed that Enteroviruses may likely be involved in the etiology of hypertension, DCM and HHF. Further studies would therefore be necessary for the prevention and control of these diseases.

  5. Enterovirus 71 Brainstem Encephalitis and Cognitive and Motor Deficits

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-12-01

    Full Text Available Follow-up studies were conducted in 63 previously healthy children with enterovirus 71 brainstem encephalitis (49 stage II, 7 stage Ilia, and 7 stage Illb at National Cheng Kung University Hospital, Tainan, Taiwan.

  6. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  7. Detection and whole genome sequence analysis of an enterovirus 68 cluster

    National Research Council Canada - National Science Library

    Todd, Angela K; Hall, Richard J; Wang, Jing; Peacey, Mathew; McTavish, Sharla; Rand, Christy J; Stanton, Jo-Ann; Taylor, Susan; Huang, Q Sue

    2013-01-01

    .... Enterovirus 68 is rarely detected yet was reported in many countries in 2010. Here enterovirus 68 was identified for the first time in New Zealand in 2010 and was detected in a further fourteen specimens over a six month period...

  8. In vitro and in vivo models for neurological complications in hand, foot and mouth disease caused by enterovirus 71 infection%肠道病毒71型感染所致手足口病神经系统并发症研究中采用的细胞系和小鼠模型

    Institute of Scientific and Technical Information of China (English)

    刘岩; 陈丽琴

    2013-01-01

    Enterovirus 71 (EV71) infection leads to hand , foot and mouth disease (HFMD) and neurological complications. It has caused many pandemics worldwide .In order to develop effective medicines and vaccines to treat HFMD caused by EV71, the researchers have been studying EV71 pathogenesis using susceptible cells and experimental animals . The in vitro and in vivo models are summarized in this paper .%手足口病在国内外已造成多次大流行,并发神经系统损害者后果较重,病死率较高.肠道病毒71型(EV71)是重症手足口病的主要病原体.为获得有效的药物及疫苗,针对EV71的感染机制和致病性,国内外学者采用体外培养细胞、实验动物等进行实验研究.本文就EV71感染所致手足口病神经系统损害的研究中所用离体细胞和小鼠模型作一综述,以期为该领域的研究提供帮助.

  9. 肠道病毒71型研究进展%STUDY ON THE PROGRESS OF ENTEROVIRUS 71

    Institute of Scientific and Technical Information of China (English)

    孙佳

    2011-01-01

    Hand, foot and mouth disease is an acute infectious disease caused by different enteroviruses. including the coxsackievirus A16 and hu-man enterovirus 71 etc. Since EV71 can cause severe central nervous system complications. This article reviewed the research progress on EV 71 , provided the basis for the prevention and treatment of HFMD.%手足口病是由不同的肠道病毒所引起的一种急性传染病,其中以柯萨奇病毒A16型和人肠道病毒EV71最为常见.由于EV71能引起严重的中枢神经系统并发症,本文就EV71的研究进展作一综述,为手足口病的预防和治疗提供依据.

  10. Coxsackievirus A21, Enterovirus 68, and Acute Respiratory Tract Infection, China

    OpenAIRE

    Xiang, Zichun; Gonzalez, Richard; Wang, Zhong; Ren, Lili; Xiao, Yan; Li, Jianguo; Li, Yongjun; Vernet, Guy; Paranhos-Baccalà, Gláucia; Jin, Qi; Wang, Jianwei

    2012-01-01

    During August 2006–April 2010, in Beijing, China, 2 rare human enterovirus serotypes, coxsackievirus A21 and enterovirus 68, were detected most frequently in human enterovirus–positive adults with acute respiratory tract infections. Thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.

  11. The absence of exanthema is related with death and illness severity in acute enterovirus infection

    Directory of Open Access Journals (Sweden)

    Hong-Tao Zhou

    2014-11-01

    Conclusions: A considerable proportion of children with an acute enterovirus infection in Guangdong Province, China during 2009–2012 presented no exanthema, and the absence of exanthema was found to be related to death and illness severity for these acute enterovirus infections. Clinicians in China should consider enterovirus as the possible pathogen when treating children with an acute pathogen infection without exanthema.

  12. Emergence of enterovirus D68 in Denmark, June 2014 to February 2015

    DEFF Research Database (Denmark)

    Midgley, S E; Christiansen, C B; Poulsen, M W

    2015-01-01

    From June 2014 through February 2015, respiratory samples from 130 Danish patients were screened for enterovirus D68 (EV-D68). Fourteen EV-D68 cases were detected, of which 12 presented with respiratory symptoms, and eight had known underlying disease. The median age of EV-D68 cases was three yea...... (interquartile range: 0–30 years). Acute flaccid paralysis (AFP) was not detected although Danish EV-D68 strains showed > 98% nt identity with EV-D68-strains from AFP cases from the United States and France....

  13. Emergence of enterovirus D68 in Denmark, June 2014 to February 2015

    DEFF Research Database (Denmark)

    Midgley, S E; Christiansen, C B; Poulsen, M W

    2015-01-01

    From June 2014 through February 2015, respiratory samples from 130 Danish patients were screened for enterovirus D68 (EV-D68). Fourteen EV-D68 cases were detected, of which 12 presented with respiratory symptoms, and eight had known underlying disease. The median age of EV-D68 cases was three yea...... (interquartile range: 0–30 years). Acute flaccid paralysis (AFP) was not detected although Danish EV-D68 strains showed > 98% nt identity with EV-D68-strains from AFP cases from the United States and France....

  14. RNA polymerase I-driven reverse genetics system for enterovirus 71 and its implications for vaccine production

    OpenAIRE

    Meng Tao; Kiener Tanja K; Kwang Jimmy

    2012-01-01

    Abstract Background Enterovirus 71 (EV71) is a virus that causes from mild hand, foot and mouth disease (HFMD) to severe neurological complications and deaths in infants and young children. Effective antiviral agents and vaccines against EV71 are not available. However, Vero cell-based chemically inactivated EV71 vaccines could be developed soon based on the success of inactivated polio vaccine. Like poliovirus, EV71 has a positive single-stranded RNA genome of about 7400 nucleotides which co...

  15. Enterovirus infections and type 1 diabetes mellitus: is there any relationship?

    Directory of Open Access Journals (Sweden)

    RG Tavares

    2012-01-01

    Full Text Available Several health organizations have classified diabetes mellitus, a metabolic syndrome, as the epidemic of the century, since it affects millions of people worldwide and is one of the top ten causes of death. Type 1 diabetes is considered to be an autoimmune disease, in which autoaggressive T cells infiltrate the islets of Langerhans in the pancreas, leading to the destruction of insulin producing beta cells. The risk of the disease is modulated by genetic factors, mainly genes coding for human leukocyte antigens (HLA. However, the incidence of this disease has increased significantly during the recent decades, which cannot be explained only by genetic factors. Environmental perturbations have also been associated to the development of diabetes. Among these factors, viral triggers have been implicated; particularly enteroviruses, which have been associated to the induction of the disease. Supporting the hypothesis, numerous lines of evidence coming from mouse models and patients with this type of diabetes have shown the association. The present review aims to provide some understanding of how type 1 diabetes occurs and the possible role of enterovirus in this pathology.

  16. Progress in Research of New Human Enterovirus Types%新型人类肠道病毒的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈鹏; 陶泽新; 王海岩; 宋艳艳; 王显军; 徐爱强

    2013-01-01

    More and more new human enteroviruses (HEVs) types were identified with the broad application of the molecular serotyping methods for enteroviruses. Since enterovirus 71 (EV71) was first reported in 1969, numerous epidemic outbreaks associated with new enteroviruses have occurred all around the world, and pose a significant threat to public health . The epidemics of hand, foot and mouth disease (HFMD) caused by EV71 infection in China have raised great concern of global scholars. This paper reviewed research progress in recent years of the molecular typing, evolution, epidemiology, and patho-genesis attributable to new enterovirus types.%随着人类肠道病毒(Human enteroviruses,HEVs)分子定型方法的广泛应用,越来越多的新型HEVs被发现.自1969年肠道病毒71型(EV71)首次报道后,新型HEVs已在世界范围内引起多次暴发流行,带来了严重的公共卫生问题,特别是自2007年以来在中国大陆发生的EV71所致手足口病的广泛流行,引起国内外学者的高度关注.本文对近些年有关新型HEVs分子分型、进化、流行病学特征、致病性等方面的研究进展进行了综述.

  17. CLINICAL AND LABORATORY CHARACTERISTICS OF THE INFECTION CAUSED BY ENTEROVIRUS-71

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    E. N. Simovanyan

    2014-01-01

    Full Text Available Adverse course of enterovirus-71 infection (EVI-71 in children, frequent development of the nervous system pathology determine the need for early disease diagnosis. The study included 139 children aged 6 months to 13 years. Modern EVI-71 features is a frequent defeat of children aged from 3 to 7 years, attending organized groups, the priority development of combined moderate severity forms without nervous system pathology. EVI-71 is characterized by cyclical course, appearance in the first two disease days fever, murrain-like, catarrhal, lymphoproliferative syndromes, conjunctivitis, headaches. The second stage of the disease (3— 6 days in 37.9% children accompanied by attaching of meningitis and meningoencephalitis symptoms (common cerebral, meningeal and encephalic syndromes, changes in cerebrospinal fluid. In the EVI-71 diagnosis must be observed epidemiological history, clinical and laboratory parameters, detection of enterovirus-71 and its RNA from feces, oropharyngeal mucus and cerebrospinal fluid. Patients with EVI-71 need for combined treatment, including causal agents and pathogenetic therapy. 

  18. Surveillance and analysis of enteroviruses in water environments in Shenzhen from 2010 to 2011.

    Science.gov (United States)

    Chen, Huiling; Liu, Qu; Wang, Dongli; Chen, Yingjian; Feng, Bin; Li, Gang; Yao, Wei; Shu, Baihua; He, Yaqing

    2013-06-01

    To determine the prevalence of enteroviruses in aquatic environments in Shenzhen, water samples were collected monthly from April 2010 to December 2011. After concentration by the filter adsorption-beef extract elution method, the enteroviruses were propagated in RD cells. Thirty-five of 105 water samples (33.33 %) were positive for cytopathic effect. E11 and E12 were the most common serotypes and had high genetic diversity in part of the VP1 region. The high prevalence of enteroviruses in water suggests that surveillance of enteroviruses in aquatic environments and evaluation of the risk associated with enteroviruses in water to public health are needed.

  19. Interference of Vaccine Derived Polio Viruses with Diagnosis of Enteroviral Diseases in Neonatal Period

    Science.gov (United States)

    Nakhaei, Alireza Ataei; Alborzi, Abdolvahab; Ziyaeyan, Mazyar

    2016-01-01

    Introduction Enteroviruses (EV) are a common cause of neonatal sepsis especially at the junction of summer and fall. Aim This study was planned to find the frequency of Enteroviral (EV) sepsis among neonates with clinical sepsis. Materials and Methods This is a prospective descriptive study. Rectal and pharyngeal swab samples were taken from all neonates with clinical sepsis and a control group of neonates with simple jaundice. EV was confirmed by both cell culture and RT-PCR. Anti polio antiserum was used to differentiate Polioviruses from Non Polio EVs (NPEV). Results We had 67 neonates with clinical sepsis and 31 cases of simple jaundice during 105 days. NPEVs were isolated from 2 cases (2.9%) of the sepsis arm and one neonate (3.2%) of the jaundice group. Polio virus was isolated from 16.2% and 15.3% of OPV recipients in the sepsis and jaundice group respectively. Conclusion Enteroviruses were not a common cause for neonatal sepsis in Nemazi hospital at the time of this study. OPV vaccinated neonates commonly pass the vaccine virus in their pharynx and stool which can be mistaken with NPEV. PMID:28050469

  20. Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein

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    Kiener Tanja K

    2012-02-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 has emerged as a major causative agent of hand, foot and mouth disease in the Asia-Pacific region over the last decade. Hand, foot and mouth disease can be caused by different etiological agents from the enterovirus family, mainly EV71 and coxsackieviruses, which are genetically closely related. Nevertheless, infection with EV71 may occasionally lead to high fever, neurologic complications and the emergence of a rapidly fatal syndrome of pulmonary edema associated with brainstem encephalitis. The rapid progression and high mortality of severe EV71 infection has highlighted the need for EV71-specific diagnostic and therapeutic tools. Monoclonal antibodies are urgently needed to specifically detect EV71 antigens from patient specimens early in the infection process. Furthermore, the elucidation of viral epitopes will contribute to the development of targeted therapeutics and vaccines. Results We have identified the monoclonal antibody 7C7 from a screen of hybridoma cells derived from mice immunized with the EV71-B5 strain. The linear epitope of 7C7 was mapped to amino acids 142-146 (EDSHP of the VP2 capsid protein and was characterized in detail. Mutational analysis of the epitope showed that the aspartic acid to asparagine mutation of the EV71 subgenogroup A (BrCr strain did not interfere with antibody recognition. In contrast, the serine to threonine mutation at position 144 of VP2, present in recently emerged EV71-C4 China strains, abolished antigenicity. Mice injected with this virus strain did not produce any antibodies against the VP2 protein. Immunofluorescence and Western blotting confirmed that 7C7 specifically recognized EV71 subgenogroups and did not cross-react to Coxsackieviruses 4, 6, 10, and 16. 7C7 was successfully used as a detection antibody in an antigen-capture ELISA assay. Conclusions Detailed mapping showed that the VP2 protein of Enterovirus 71 contains a single, linear, non

  1. Enterovirus Control of Translation and RNA Granule Stress Responses

    Directory of Open Access Journals (Sweden)

    Richard E. Lloyd

    2016-03-01

    Full Text Available Enteroviruses such as poliovirus (PV and coxsackievirus B3 (CVB3 have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs and processing bodies (P-bodies, PBs, which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

  2. Enterovirus Control of Translation and RNA Granule Stress Responses

    Science.gov (United States)

    Lloyd, Richard E.

    2016-01-01

    Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation. PMID:27043612

  3. Progress in the research of enterovirus 71%肠道病毒71型的研究进展

    Institute of Scientific and Technical Information of China (English)

    顾文珍

    2010-01-01

    Enterovirus 71 (EV71) is one of the main pathogens of hand, foot and mouth disease resulting in severe neurological complications and fatality. In fact, EV71 has been regarded as the most important neurotropic enterovirus after eradication of poliovirus. This paper reviews predisposing factors of EV71 infection and progress in the research of EV71 vaccine, thus pointing out the way for prevention and control of EV71 infection.%肠道病毒71型(enterovirus 71,EV71)是引起手足口病(hand,foot and mouth disease,HFMD)的主要病原体之一,HFMD可并发严重神经系统疾病,甚至导致死亡.事实上,EV71一直被视为继脊髓灰质炎病毒消灭后最重要的嗜神经病毒.此文就EV71感染的易感因素以及疫苗的研究进展进行综述,从而为EV71感染的防控指明方向.

  4. Neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease:clinical features, MRI findings and follow-up study%小儿肠道病毒71型感染手足口病合并神经系统损伤的临床、MRI特征及随访研究

    Institute of Scientific and Technical Information of China (English)

    刘锟; 马炎旭; 张呈兵; 陈益平; 叶信健; 白光辉; 虞志康; 严志汉

    2012-01-01

    目的 探讨肠道病毒71(EV71)相关手足口病(HFMD)合并中枢神经系统损伤的临床及MRI特征.方法 回顾性分析2008年8月至2010年11月温州医学院附属第二医院的35例伴有神经系统损伤的EV71感染HFMD患儿临床、发病初及随访时MRI资料,并总结其临床、MRI及随访特点.结果 35例中,6例合并无菌性脑膜炎,临床存在脑膜炎症状及体征,5例MRI表现为硬膜下腔增宽和(或)脑室扩大,随访时无神经系统后遗症.24例合并脑干脑炎,其中I级12例表现为肌阵挛合并震颤和(或)共济失调,Ⅱ级4例表现为肌阵挛及颅神经受累,Ⅲ级8例表现为中枢受累后心肺衰竭.其MRI主要表现为脑干背侧异常长T1长T2信号,可伴有小脑齿状核、尾状核及豆状核受累.随访时,临床表现较轻者无神经系统后遗症,脑干病灶多吸收消失,重者残留神经系统后遗症,脑干病灶多吸收变小、软化.9例合并急性弛缓性瘫痪,相应肢体肌力下降、肌张力减弱、腱反射减弱或消失.MRI表现为脊髓前角区长T1长T2信号灶.随访时受累肢体肌力得到不同程度的恢复,脊髓病灶多吸收好转.结论 MRI是评价EV71感染HFMD神经系统损害及观察预后的有效影像手段,影像表现具有相对特异性,损害部位常位于脑干背侧、脊髓前角.经积极治疗后,随访时患儿多无神经系统后遗症,其神经系统病灶多明显吸收.%Objective To explore the clinical and magnetic resonance imaging(MRI)characteristics and the follow-up outcomes of neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease.Methods The clinical and MRI manifestations and follow-up outcomes in 35 children,at Second Affiliated Hospital,Wenzhou Medical College from August 2008 to November 2010,hospitalized with neurologic complications of enterovirus 71-infected hand-foot-mouth disease were retrospectively analyzed.Results Six children with aseptic meningitis

  5. Seroepidemiological and phylogenetic characterisation of neurotropic enteroviruses in Ireland, 2005-2014.

    Science.gov (United States)

    Guerra, Jorge Abboud; Waters, Allison; Kelly, Alison; Morley, Ursula; O'Reilly, Paul; O'Kelly, Edwin; Dean, Jonathan; Cunney, Robert; O'Lorcain, Piaras; Cotter, Suzanne; Connell, Jeff; O'Gorman, Joanne; Hall, William W; Carr, Michael; De Gascun, Cillian F

    2017-01-10

    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 enterovirus D68 (EV-D68). EV VP1 genotyping was applied to viral isolates and clinical samples, including cerebrospinal fluid (CSF), and those isolates that remained untypeable by neutralising anti-sera. An increase in AM cases from 2010-2014 was associated with an E-30 genogroup variant VII and sequences clustered phylogenetically with those detected in AM outbreaks in France and Italy. EV-D68 viral RNA was not detected in CSF samples and no neurological involvement was reported. Three EVA71 positive CSF samples were identified in patients presenting with aseptic meningitis. A phylogenetic analysis of respiratory-associated EV-D68 and EV-A71 cases in circulation was performed to determine baseline epidemiological data. EV-D68 segregated with clades B and B(1) and EV-A71 clustered as subgenogroup C2. The EV VP1 genotyping method was more sensitive than neutralising anti-sera methods by virus culture and importantly demonstrated concordance between EV genotypes in faecal and CSF samples which should facilitate EV screening by less invasive sampling approaches in AM presentations. This article is protected by copyright. All rights reserved.

  6. Enterovirus 71 infection: An experience in Korea, 2009

    Directory of Open Access Journals (Sweden)

    Kyung Hyo Kim

    2010-05-01

    Full Text Available Enterovirus 71 (EV71 has been recognized as a frequent cause of epidemics of hand-foot-and-mouth disease (HFMD associated with severe neurological symptoms. In the spring of 2009, HFMD was epidemic in Korea. Severe cases with complication, including death, have been reported and it has become a public health issue. Most symptomatic EV71 infections commonly result in HFMD or herpangina. These clinical manifestations can be associated with neurologic syndromes frequently. Neurologic syndromes observed in EV71 include meningitis, meningoencephalomyelitis, poliomyelitis-like paralytic disease, Guillain-Barr&eacute; syndrome, transverse myelitis, cerebellar ataxia, opsoclonus-myoclonus syndrome, benign intracranial hypertension, and brainstem encephalitis. Examinations for EV 71 were performed from the stools, respiratory secretion or CSF of the children by realtime PCR. Gene analysis showed that most of them were caused by EV71 subgenotype C4a which was prevalent in China, 2008. Public health measures including personal and environmental hygiene, must to target daycare centers, kindergartens, and schools where highly susceptible children congregate. To prevent the spread of infection, preschools where transmission persists for more than 2 incubation periods, have been recommended for closure, and trigger criteria for voluntary closure was instituted. During closure, operators are to thoroughly clean the centers before they are allowed to reopen. In addition, parents are advised to ensure that their children adopt a high standard of personal hygiene and to keep the infected child at home until full recovery. Because the outbreaks occur in a cyclical pattern, surveillance system to predict next outbreaks and adequate public health measures to control need to be planned for future. Control of EV71 epidemics through surveillance and public health intervention needs to be maintained in Korea. Future research should focus on understanding of EV71

  7. The interplays between autophagy and apoptosis induced by enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Xueyan Xi

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 is the causative agent of human diseases with distinct severity, from mild hand, foot and mouth disease to severe neurological syndromes, such as encephalitis and meningitis. The lack of understanding of viral pathogenesis as well as lack of efficient vaccine and drugs against this virus impedes the control of EV71 infection. EV71 virus induces autophagy and apoptosis; however, the relationship between EV71-induced autophagy and apoptosis as well as the influence of autophagy and apoptosis on virus virulence remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it was observed that the Anhui strain of EV71 induced autophagy and apoptosis in human rhabdomyosarcoma (RD-A cells. Additionally, by either applying chemical inhibitors or knocking down single essential autophagic or apoptotic genes, inhibition of EV71 induced autophagy inhibited the apoptosis both at the autophagosome formation stage and autophagy execution stage. However, inhibition of autophagy at the stage of autophagosome and lysosome fusion promoted apoptosis. In reverse, the inhibition of EV71-induced apoptosis contributed to the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I to LC3-II and degradation of sequestosome 1 (SQSTM1/P62. Furthermore, the inhibition of autophagy in the autophagsome formation stage or apoptosis decreased the release of EV71 viral particles. CONCLUSIONS/SIGNIFICANCE: In conclusion, the results of this study not only revealed novel aspect of the interplay between autophagy and apoptosis in EV71 infection, but also provided a new insight to control EV71 infection.

  8. Enterovirus D68 receptor requirements unveiled by haploid genetics.

    Science.gov (United States)

    Baggen, Jim; Thibaut, Hendrik Jan; Staring, Jacqueline; Jae, Lucas T; Liu, Yue; Guo, Hongbo; Slager, Jasper J; de Bruin, Jost W; van Vliet, Arno L W; Blomen, Vincent A; Overduin, Pieter; Sheng, Ju; de Haan, Cornelis A M; de Haan Xander, Cornelis A M; de Vries, Erik; Meijer, Adam; Rossmann, Michael G; Brummelkamp, Thijn R; van Kuppeveld, Frank J M

    2016-02-01

    Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory disease and is associated with cases of paralysis, especially among children. Heretofore, information on host factor requirements for EV-D68 infection is scarce. Haploid genetic screening is a powerful tool to reveal factors involved in the entry of pathogens. We performed a genome-wide haploid screen with the EV-D68 prototype Fermon strain to obtain a comprehensive overview of cellular factors supporting EV-D68 infection. We identified and confirmed several genes involved in sialic acid (Sia) biosynthesis, transport, and conjugation to be essential for infection. Moreover, by using knockout cell lines and gene reconstitution, we showed that both α2,6- and α2,3-linked Sia can be used as functional cellular EV-D68 receptors. Importantly, the screen did not reveal a specific protein receptor, suggesting that EV-D68 can use multiple redundant sialylated receptors. Upon testing recent clinical strains, we identified strains that showed a similar Sia dependency, whereas others could infect cells lacking surface Sia, indicating they can use an alternative, nonsialylated receptor. Nevertheless, these Sia-independent strains were still able to bind Sia on human erythrocytes, raising the possibility that these viruses can use multiple receptors. Sequence comparison of Sia-dependent and Sia-independent EV-D68 strains showed that many changes occurred near the canyon that might allow alternative receptor binding. Collectively, our findings provide insights into the identity of the EV-D68 receptor and suggest the possible existence of Sia-independent viruses, which are essential for understanding tropism and disease.

  9. Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Juan [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Microbiology and Immunology, Nanjing Medical University (China); Wang, Shixia [China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States); Gan, Weihua [Department of Pediatrics, The Second Affiliated Hospital, Nanjing Medical University (China); Zhang, Wenhong [Department of Infectious Diseases, Huashan Hospital, Fudan University (China); Ju, Liwen [School of Public Health, Fudan University (China); Huang, Zuhu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Lu, Shan, E-mail: shan.lu@umassmed.edu [Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University (China); China-US Vaccine Research Center, The First Affiliated Hospital, Nanjing Medical University (China); Department of Medicine, University of Massachusetts Medical School (United States)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer EV71 is a major emerging infectious disease in many Asian countries. Black-Right-Pointing-Pointer Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. Black-Right-Pointing-Pointer Developing subunit based EV71 vaccines is significant and novel antigen design is needed. Black-Right-Pointing-Pointer DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. Black-Right-Pointing-Pointer Multiple VP1 antigens are developed showing immunogenic potential. -- Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71 (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.

  10. A one-step, triplex, real-time RT-PCR assay for the simultaneous detection of enterovirus 71, coxsackie A16 and pan-enterovirus in a single tube.

    Directory of Open Access Journals (Sweden)

    Shiyin Zhang

    Full Text Available The recent, ongoing epidemic of hand, foot, and mouth disease (HFMD, which is caused by enterovirus infection, has affected millions of children and resulted in thousands of deaths in China. Enterovirus 71 (EV71 and coxsackie A16 (CA16 are the two major distinct pathogens for HFMD. However, EV71 is more commonly associated with neurologic complications and even fatalities. Therefore, simultaneously detecting and differentiating EV71 and CA16 specifically from other enteroviruses for diagnosing HFMD is important. Here, we developed a one-step, triplex, real-time RT-PCR assay for the simultaneous detection of EV71, CA16, and pan-enterovirus (EVs in a single tube with an internal amplification control. The detection results for the serially diluted viruses indicate that the lower limit of detection for this assay is 0.001-0.04 TCID50/ml, 0.02 TCID50/ml, and 0.001 TCID50/ml for EVs, EV71, and CA16, respectively. After evaluating known HFMD virus stocks of 17 strains of 16 different serotypes, this assay showed a favorable detection spectrum and no obvious cross-reactivity. The results for 141 clinical throat swabs from HFMD-suspected patients demonstrated sensitivities of 98.4%, 98.7%, and 100% for EVs, EV71, and CA16, respectively, and 100% specificity for each virus. The application of this one-step, triplex, real-time RT-PCR assay in clinical units will contribute to HFMD surveillance and help to identify causative pathogen in patients with suspected HFMD.

  11. Anti-Enterovirus 71 Agents of Natural Products

    Directory of Open Access Journals (Sweden)

    Liyan Wang

    2015-09-01

    Full Text Available 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.

  12. Enterovirus and type 1 diabetes: What is the matter?

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    A complex interaction of genetic and environmentalfactors can trigger the immune-mediated mechanismresponsible for type 1 diabetes mellitus (T1DM)establishment. Environmental factors may initiate andpossibly sustain, accelerate, or retard damage to β-cells.The role of environmental factors in this processhas been exhaustive studied and viruses are amongthe most probable ones, especially enteroviruses.Improvements in enterovirus detection methods and randomized studies with patient follow-up haveconfirmed the importance of human enterovirusin the pathogenesis of T1DM. The genetic risk ofT1DM and particular innate and acquired immuneresponses to enterovirus infection contribute to atolerance to T1DM-related autoantigens. However,the frequency, mechanisms, and pathways of virallyinduced autoimmunity and β-cell destruction in T1DMremain to be determined. It is difficult to investigatethe role of enterovirus infection in T1DM because ofseveral concomitant mechanisms by which the virusdamages pancreatic β-cells, which, consequently, maylead to T1DM establishment. Advances in molecularand genomic studies may facilitate the identificationof pathways at earlier stages of autoimmunity whenpreventive and therapeutic approaches may be moreeffective.

  13. Upsurge of Enterovirus D68, the Netherlands, 2016

    Science.gov (United States)

    Schölvinck, Elisabeth H.; Poelman, Randy; Smit, Sylvia; Vermont, Clementien L.; Niesters, Hubert G.M.; Van Leer-Buter, Coretta C.

    2017-01-01

    In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3. PMID:27660916

  14. 不同病程手足口病患者咽拭、肛拭配对标本肠道病毒检出率的比较%Comparison of enterovirus detection rates in paired specimens of throat swabs and anus swabs from patients in different phases of hand-foot-mouth disease

    Institute of Scientific and Technical Information of China (English)

    李颐; 居丽雯; 蒋露芳; 沈磊; 赵文良; 沈琦; 蔡明毅; 孟威; 姜庆五

    2013-01-01

    目的 比较不同病程手足口病患者咽拭、肛拭配对标本中肠道病毒的检出率.方法 采集2010年7月至2011年12月上海市儿童医院临床诊断手足口病患儿175例咽拭、肛拭配对标本,采用实时-PCR法进行柯萨奇病毒A组16型(CoxA16)、肠道病毒71型(EV71)和其他EV属检测,分析不同病程配对标本肠道病毒检出率.配对标本行McNemar检验.结果 175例患者的配对标本CoxA 16、EV71、其他EV属咽拭子阳性率分别为38.29%、20.57%和8.00%,肛拭子阳性率分别为44.00%、23.43%和13.14%.结果显示两种标本检测结果的差异均有统计学意义(均P<0.01).发病当天至发病后2d及4~11 d肛拭EV71阳性率均比咽拭阳性率高;发病后2~3d肛拭CoxA 16阳性率均比咽拭阳性率高;发病当天至发病后3d肛拭其他EV属阳性率均比咽拭阳性率高.对于EV71,咽拭标本在发病后3~11 d均可检出阳性,而CoxA 16、其他EV属在发病3d后都无法检出阳性.结论 肛拭标本总体阳性率高于咽拭标本.EV71在呼吸道带毒持续时间长于CoxA 16和其他EV属.在发病2d内肠道病毒在咽部繁殖扩增,此时病毒可通过呼吸道途径传播.%Objective To compare the detection rates of enterovirus in paired specimens of throat swabs and anus swabs from patients with different phases of hand-food-mouth disease (HFMD).Methods A total of 175 paired throat swabs and anus swabs from patients who were clinically diagnosed with HFMD in Children's Hospital of Shanghai from July 2010 to December 2011 were collected.Real-time reverse transcription polymerase chain reaction (RT-PCR) to detect Enterovirus 71 (EV71),Coxsackievirus group A type 16 (CoxA16) and other Enterovirus(EV) was performed.The detection rates of paired specimens within different phases of the disease were compared.Results Among the 175 pairs of specimens,the positive rates of CoxA16,EV71 and other EV in throat swabs were 38.29%,20.57% and 8.00

  15. High immunogenic enterovirus 71 strain and its production using serum-free microcarrier Vero cell culture.

    Science.gov (United States)

    Liu, Chia-Chyi; Lian, Wei-Cheng; Butler, Michael; Wu, Suh-Chin

    2007-01-01

    Developing an effective vaccine against enterovirus 71 (EV71) infection provides the best means to control the disease. We have previously reported that large-scale preparation of a low immunogenic EV71 strain can be achieved using serum free microcarrier Vero cell culture in a 2-l bioreactor [Wu SC, Liu CC, Lian WC. Optimization of microcarrier cell culture process for the inactivated enterovirus type 71 vaccine development. Vaccine 2004;22:3858-64]. This present work further investigated the virus growth and the immunogenicity of two high immunogenic strains (EV71-075 and EV71-117) prepared in serum-free microcarrier cell cultures. Our results showed that serum free culture increased cell death rate after infection, reduced the virus specific productivity, but resulted in elicitation of higher neutralizing titers in immunized mice as compared to that parallel obtained in serum-containing cultures. Therefore, serum-free microcarrier culture is a valuable process for developing inactivated EV71 vaccines.

  16. The Golgi protein ACBD3 facilitates Enterovirus 71 replication by interacting with 3A

    Science.gov (United States)

    Lei, Xiaobo; Xiao, Xia; Zhang, Zhenzhen; Ma, Yijie; Qi, Jianli; Wu, Chao; Xiao, Yan; Zhou, Zhuo; He, Bin; Wang, Jianwei

    2017-01-01

    Enterovirus 71 (EV71) is a human pathogen that causes hand, foot, mouth disease and neurological complications. Although EV71, as well as other enteroviruses, initiates a remodeling of intracellular membrane for genomic replication, the regulatory mechanism remains elusive. By screening human cDNA library, we uncover that the Golgi resident protein acyl-coenzyme A binding domain-containing 3 (ACBD3) serves as a target of the 3A protein of EV71. This interaction occurs in cells expressing 3A or infected with EV71. Genetic inhibition or deletion of ACBD3 drastically impairs viral RNA replication and plaque formation. Such defects are corrected upon restoration of ACBD3. In infected cells, EV71 3A redirects ACBD3, to the replication sites. I44A or H54Y substitution in 3A interrupts the binding to ACBD3. As such, viral replication is impeded. These results reveal a mechanism of EV71 replication that involves host ACBD3 for viral replication. PMID:28303920

  17. A dominant EV71-specific CD4+ T cell epitope is highly conserved among human enteroviruses.

    Directory of Open Access Journals (Sweden)

    Ruicheng Wei

    Full Text Available CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD, has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine.

  18. Enterovirus A71 Meningoencephalitis Outbreak, Rostov-on-Don, Russia, 2013

    Science.gov (United States)

    Akhmadishina, Ludmila V.; Govorukhina, Marina V.; Kovalev, Evgeniy V.; Nenadskaya, Svetlana A.; Ivanova, Olga E.

    2015-01-01

    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. PMID:26196217

  19. Enterovirus A71 Meningoencephalitis Outbreak, Rostov-on-Don, Russia, 2013.

    Science.gov (United States)

    Akhmadishina, Ludmila V; Govorukhina, Marina V; Kovalev, Evgeniy V; Nenadskaya, Svetlana A; Ivanova, Olga E; Lukashev, Alexander N

    2015-08-01

    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.

  20. Establishment of a panel of in-house polyclonal antibodies for the diagnosis of enterovirus infections.

    Science.gov (United States)

    Kotani, Osamu; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Sato, Yuko; Nakajima, Noriko; Koike, Satoshi; Iwasaki, Takuya; Sata, Tetsutaro; Yamashita, Teruo; Minagawa, Hiroko; Taguchi, Fumihiro; Hasegawa, Hideki; Shimizu, Hiroyuki; Nagata, Noriyo

    2015-04-01

    The aim of this study was to establish a reliable method of virus detection for the diagnosis of critical enterovirus infections such as acute infective encephalitis, encephalomyelitis and myocarditis. Because histopathological and immunohistochemical analyses of paraffin-embedded tissues play an important role in recognizing infectious agents in tissue samples, six in-house polyclonal antibodies raised against three representative enteroviruses using an indirect immunofluorescence assay and immunohistochemistry were examined. This panel of polyclonal antibodies recognized three serotypes of enterovirus. Two of the polyclonal antibodies were raised against denatured virus particles from enterovirus A71, one was raised against the recombinant VP1 protein of coxsackievirus B3, and the other for poliovirus type 1 were raised against denatured virus particles, the recombinant VP1 protein and peptide 2C. Western blot analysis revealed that each of these antibodies recognized the corresponding viral antigen and none cross-reacted with non-enteroviruses within the family Picornaviridae. However, all cross-reacted to some extent with the antigens derived from other serotypes of enterovirus. Indirect immunofluorescence assay and immunohistochemistry revealed that the virus capsid and non-structural proteins were localized in the cytoplasm of affected culture cells, and skeletal muscles and neurons in neonatal mice experimentally-infected with human enterovirus. The antibodies also recognized antigens derived from recent clinical isolates of enterovirus A71, coxsackievirus B3 and poliovirus. In addition, immunohistochemistry revealed that representative antibodies tested showed the same recognition pattern according to each serotype. Thus, the panel of in-house anti-enterovirus polyclonal antibodies described herein will be an important tool for the screening and pathological diagnosis for enterovirus infections, and may be useful for the classification of different

  1. Apigenin inhibits enterovirus 71 replication through suppressing viral IRES activity and modulating cellular JNK pathway.

    Science.gov (United States)

    Lv, Xiaowen; Qiu, Min; Chen, Deyan; Zheng, Nan; Jin, Yu; Wu, Zhiwei

    2014-09-01

    Enterovirus 71 (EV71) is a member of genus Enterovirus in Picornaviridae family, which is one of the major causative agents for hand, foot and mouth disease (HFMD), and sometimes associated with severe central nervous system diseases in children. Currently there are no effective therapeutic medicines or vaccines for the disease. In this report, we found that apigenin and luteolin, two flavones that differ only in the number of hydroxyl groups could inhibit EV71-mediated cytopathogenic effect (CPE) and EV71 replication with low cytotoxicity. Both molecules also showed inhibitory effect on the viral polyprotein expression. They prevented EV71-induced cell apoptosis, intracellular reactive oxygen species (ROS) generation and cytokines up-regulation. Time-of-drug addition study demonstrated that apigenin and luteolin acted after viral entry. We examined the effect of apigenin and luteolin on 2A(pro) and 3C(pro) activity, two viral proteases responsible for viral polyprotein processing, and found that they showed less inhibitory activity on 2A(pro) or 3C(pro). Further studies demonstrated that apigenin, but not luteolin could interfere with viral IRES activity. Also, apigenin inhibited EV71-induced c-Jun N-terminal kinase (JNK) activation which is critical for viral replication, in contrast to luteolin that did not. This study demonstrated that apigenin may inhibit EV71 replication through suppressing viral IRES activity and modulating cellular JNK pathway. It also provided evidence that one hydroxyl group difference in the B ring between apigenin and luteolin resulted in the distinct antiviral mechanisms. This study will provide the basis for better drug development and further identification of potential drug targets.

  2. 地表水中肠道病毒检测结果分析%Detection of human enteroviruses in surface water

    Institute of Scientific and Technical Information of China (English)

    谭惠玲; 刘春平; 刘凤仁; 刘渠; 李水明; 李刚; 陈应坚; 叶伟雄

    2012-01-01

    目的 了解某地地表水中EV71、CoxA16等人肠道病毒的污染情况.方法 选择某地1个污水处理厂和1条河流(上、下游)作为采样对象,每月采集未经处理的污水和上、下游河水各1份,经过滤、浓缩后进行人肠道病毒核酸检测.结果 36份水样中,肠道病毒检出率为52.77%;其中EV71阳性检出率为44.44%,CoxA16阳性检出率为16.66%,其它肠道病毒的检出率亦高达36.11%.夏季地表水体中的肠道病毒阳性率(100.00%)显著高于其它季节(37.03%)(P<0.00).污水中各类肠道病毒的检出率与河水中肠道病毒的检出率差异无统计学意义(P>0.05).地表水中肠道病毒的检出率与当地手足口病、手足口病重症及肠道传染病(甲乙丙类)的发生无相关(P>0.05).结论 地表水中肠道病毒的污染严重,有必要开展进一步的研究了解肠道病毒经水传播的风险.%Objective To understand the human enteroviruses contamination in surface water in a certain district. Methods Water samples from a sewage treatment plant and river (Upstream and downstream) were collected for viral nucleic acid detection of enteroviruses once a month. Results The detection rate of enteroviruses was 52.77% in surface water, with detection rate of enterovirus 71(EV71) 44.44%, Coxsackie A16(CoxA16) 16.66% and other enterovirus 36.11%. The detection rate of enteroviruses in surface water in summer was significantly higher than those of other seasons. Compared with river water, the detection rate of all kinds of enteroviruses in sewage was similar to river water(P>0.05). No relationship was found between the detection rate of enteroviruses and the incidence of hand-foot-mouth disease, severe hand-foot-mouth disease and intestinal diseases (P>0.05). Conclusion The surface water was serious polluted with human enteroviruses. It is necessary to conduct further research for the prediction of spread risk of intestinal viruses through surface waters.

  3. [100 years of studying poliomyelitis virus and nonpoliomyelitis enteroviruses].

    Science.gov (United States)

    Lashkevich, V A

    2008-01-01

    M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitis, Russian Academy of Medical Sciences, Moscow The paper deals with the history of discovery of poliomyelitis virus by K. Landsteiner and E. Popper in 1908, the identification of three immunological types of the virus in 1949, the discovery of viral multiplication in the cultures of non-nerve cells with a cytopathogenic effect by A. Anders in 1949, the development of new diagnostic techniques, the design of inactivated poliovirus vaccine by D. Salk in 1953 and its live vaccine by A. Sabin in 1957. The advantages and disadvantages of these vaccines and the prospects for further poliomyelitis control are discussed. The characteristics and role of nonpoliomyelitis enteroviruses are considered. The most important scientific discoveries made in the study of enteroviruses are noted.

  4. Typing of enteroviruses by use of microwell oligonucleotide arrays.

    Science.gov (United States)

    Susi, P; Hattara, L; Waris, M; Luoma-Aho, T; Siitari, H; Hyypiä, T; Saviranta, P

    2009-06-01

    We have developed a straightforward assay for the rapid typing of enteroviruses using oligonucleotide arrays in microtiter wells. The viral nucleic acids are concomitantly amplified and labeled during reverse transcription-PCR, and unpurified PCR products are used for hybridization. DNA strands are separated by alkaline denaturation, and hybridization is started by neutralization. The microarray hybridization reactions and the subsequent washes are performed in standard 96-well microtiter plates, which makes the method easily adaptable to high-throughput analysis. We describe here the assay principle and its potential in clinical laboratory use by correctly identifying 10 different enterovirus reference strains. Furthermore, we explore the detection of unknown sequence variants using serotype consensus oligonucleotide probes. With just two consensus probes for the coxsackievirus A9 (CVA9) serotype, we detected 23 out of 25 highly diverse CVA9 isolates. Overall, the assay involves several features aiming at ease of performance, robustness, and applicability to large-scale studies.

  5. Genetic evolution of enterovirus 71: epidemiological and pathological implications.

    Science.gov (United States)

    Bible, Jon M; Pantelidis, Panagiotis; Chan, Paul K S; Tong, C Y William

    2007-01-01

    Since its discovery in the 1970s, enterovirus 71 (EV71) has become one of the most pathogenic enterovirus serotypes causing recurrent outbreaks in different parts of the world. Three waves of outbreaks globally have been recorded over the last three decades and more recently active circulation of EV71 is evident amongst countries in South East Asia and beyond. There is evidence of a continuous evolution in its genetic make up which is likely to impact on its epidemiology and pathological potential. This review examines the molecular genetics and evolution of EV71 in relation to its epidemiological and pathological properties. A thorough understanding of the relationship between the genetic changes and the resulting host-virus interaction is essential for successful control.

  6. Reemergence of Enterovirus 71 Epidemic in Northern Taiwan, 2012

    OpenAIRE

    Shu-Ting Luo; Pai-Shan Chiang; Wan-Yu Chung; Min-Yuan Chia; Kuo-Chien Tsao; Ying-Hsiang Wang; Tzou-Yien Lin; Min-Shi Lee

    2015-01-01

    Background Enterovirus 71 (EV71) belongs to picornavirus family and could be classified phylogenetically into three major genogroups (A, B and C) including 11 genotypes (A, B1-B5 and C1-C5). Since 1997, EV71 has caused large-scale of epidemics with neurological complications in Asian children. In Taiwan, nationwide EV71 epidemics with different predominant genotypes have occurred cyclically since 1998. A nationwide EV71 epidemic occurred again in 2012. We conducted genetic and antigenic chara...

  7. Reemergence of enterovirus 71 epidemic in northern Taiwan, 2012.

    Directory of Open Access Journals (Sweden)

    Shu-Ting Luo

    Full Text Available Enterovirus 71 (EV71 belongs to picornavirus family and could be classified phylogenetically into three major genogroups (A, B and C including 11 genotypes (A, B1-B5 and C1-C5. Since 1997, EV71 has caused large-scale of epidemics with neurological complications in Asian children. In Taiwan, nationwide EV71 epidemics with different predominant genotypes have occurred cyclically since 1998. A nationwide EV71 epidemic occurred again in 2012. We conducted genetic and antigenic characterizations of the 2012 epidemic.Chang Gung Memorial Hospital (CGMH is a medical center in northern Taiwan. In CGMH, specimens were collected from pediatric inpatients with suspected enterovirus infections for virus isolation. Enterovirus isolates were serotyped and genotyped and sera from EV71 inpatients were collected for measuring neutralizing antibody titers.There were 10, 16 and 99 EV71 inpatients identified in 2010, 2011 and 2012, respectively. There were 82 EV71 isolates genotyped, which identified 17 genotype C4a viruses and 65 genotype B5 viruses. The genotype B5 viruses were not detected until November 2011 and caused epidemics in 2012. Interestingly, the B5-2011 viruses were genetically distinguishable from the B5 viruses causing the 2008 epidemic and are likely introduced from China or Southeastern Asia. Based on antigenic analysis, minor antigenic variations were detected among the B5-2008, B5-2011, C4a-2008 and C4a-2012 viruses but these viruses antigenically differed from genotype A.Genotype B5 and C4a viruses antigenically differ from genotype A viruses which have disappeared globally for 30 years but have been detected in China since 2008. Enterovirus surveillance should monitor genetic and antigenic variations of EV71.

  8. Surveillance for enteroviruses in healthy children in Yunnan Province from 2014 to 2015%2014-2015年云南省健康儿童肠道病毒带毒状况调查

    Institute of Scientific and Technical Information of China (English)

    田子颖; 唐婷婷; 李凯; 丁峥嵘; 张杰; 田炳均

    2016-01-01

    /921) and all of them were Sabin-like polioviruses. The rest of the strains were non-polio enterovirus (7. 93%, 73/921). Conclusion In 2014, the EV isolating rate in inner counties (9. 39%) was higher than that in border counties (6. 67%). However, the EV isolating rate in border counties (12. 09%) was higher than that in inner counties (6. 67%) in 2015. Enterovirus B was the predominant species in both 2014 and 2015. No wild type polioviruses and enterovirus D species were detec-ted. Polio-free status was maintained well in Yunnan Province.%目的:了解2014—2015年云南省健康儿童中肠道病毒( enterovirus, EV)带毒情况和病毒型别,并对埃可病毒6型(echovirus type 6, ECHO6)、ECHO25和ECHO11的基因特征进行分析。方法采集3个内地州(市)6~7个县及5个边境州8~9个县<15岁健康儿童粪便标本共921份进行病毒分离和基因测序定型,其中2014年共采集453份(均为单份便,其中内地儿童213份,边境儿童240份),2015年共采集468份(内地儿童195份,边境儿童273份)。结果2014年,从内地儿童粪便标本中分离到EV 20株,分离率为9.39%(20/213),从边境儿童中分离到EV 16株,分离率为6.67%(16/240)。2014年病毒总体分离率为7.95%(36/453)。从病毒型别来看,B种病毒分离率最高(88.89%,32/36),其次为A种病毒(11.11%,4/36),未分离到C种(包括脊髓灰质炎病毒)和D种病毒。2015年,从内地儿童粪便标本中分离到EV 13株,分离率为6.67%(13/195),从边境儿童中分离到EV 33株,分离率为12.09%(33/273)。2015年病毒总体分离率为9.83%(46/468)。从病毒型别来看,B 种病毒分离率最高(78.26%,36/46),其次为 C 种病毒(19.57%,9/46)和 A 种病毒(2.17%,1/46),未分离到 D 种病毒。两年共从921份粪便标本中检测到 EV 82株(分离率为8.90%,82/921),其中,从内地儿童分离到33株,分离率为8.09%(33/408),从边境儿童中分离到EV 49株,分离率为9.55%(49/513)。82株EV中,脊髓灰质炎病毒(poliovirus, PV)9

  9. Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

    Directory of Open Access Journals (Sweden)

    Qin Chuan

    2011-10-01

    Full Text Available Abstract Human enterovirus 71 (EV71 infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE on rhabdomyosarcoma (RD cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.

  10. Anti-enterovirus 71 effects of chrysin and its phosphate ester.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71 can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. The anti-EV71 effect of chrysin (5,7-dihydroxyflavone, a natural flavonoid commonly found in many plants, was tested in this report. By using the predicting program Autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3Cpro activity. Replication of viral RNA and production of viral capsid protein and the infectious virion were strongly inhibited by chrysin, without noticeable cytotoxicity. Cytopathic effects on cells were also prevented. Diisopropyl chrysin-7-yl phosphate (CPI, the phosphate ester for chrysin, was generated through a simplified Atheron-Todd reaction to achieve stronger anti-viral activity. CPI was also able to bind with and inhibit viral 3Cpro activity in vitro. As expected, CPI demonstrated more potent antiviral activity against EV71.

  11. Detection of enterovirus RNA in cerebrospinal fluid : Comparison of two molecular assays

    NARCIS (Netherlands)

    de Crom, S. C. M.; Obihara, C. C.; van Loon, A. M.; Argilagos-Alvarez, A. A.; Peeters, M. F.; van Furth, A. M.; Rossen, J. W. A.

    2012-01-01

    Enterovirus (EV) and human parechovirus (HPeV) are a major cause of infection in childhood. A rapid diagnostic test may improve the management of patients with EV and HPeV infection. The aim of this study is to evaluate the performance of the GeneXpert enterovirus assay (GXEA) for detection of EV RN

  12. Epidemiologic aspects and laboratory features of enterovirus infections in Western Germany, 2000-2005.

    Science.gov (United States)

    Roth, Bernhard; Enders, Martin; Arents, Annette; Pfitzner, Artur; Terletskaia-Ladwig, Elena

    2007-07-01

    From 2000 to 2005, a total of 1,096 enterovirus infections were diagnosed either by isolation of virus from cell culture or by RT-PCR (5'non-coding region (NCR)). Typing of viruses (n = 674) was carried out by immunofluorescence with monoclonal antibodies, neutralization test or molecular methods. Seasons with high enterovirus activity were characterized by high prevalence of echovirus 30 (62.2% in 2000, 25.5% in 2001) and echovirus 13 (34.5% in 2001). In contrast, in the 2003 season, which had very low enterovirus activity, these types were rare. During this season, cell culture sensitivity (human colonic carcinoma cells and human embryonic lung fibroblasts (HEL)) was exceptionally low. In order to determine the type of "non-cultivable" enteroviruses, purified RNA from selected stool samples was subjected to direct molecular typing. VP1/2A-specific fragments were amplified by RT-PCR, cloned and sequenced. The predominant virus identified was coxsackie A. Consequently, rhabdomyosarcom cells were introduced into the daily routine, which improved the isolation of enteroviruses. Echovirus 30 was again most commonly isolated during seasons 2004 and 2005 with increasing enterovirus activity. In conclusion, high prevalence of echovirus 30 and 13 is indicative of seasons with high enterovirus activity. The type of circulating enteroviruses may influence isolation of enterovirus from cell culture. RT-PCR (VP1/2A) combined with cloning and sequencing of amplicons is a useful tool for viral typing directly from stool samples. In cases of severe enterovirus infection, virological diagnosis should not solely rely on virus isolation from cell culture.

  13. Genetic Analysis of the P1 Region of Human Enterovirus 71 Strains and Expression of the 55 F StrainVP1 Protein

    Institute of Scientific and Technical Information of China (English)

    Jian-qiang Li; Jun-jie Yang; Xiu-juan Fan; Zhen-peng Sun; Yan Sun; Huan Li; Zi-xin Meng; Wei Li

    2012-01-01

    Enterovirus 71 (EV71) is a member of the Entero-virus genus of the Picornaviridae family and is the major cause of Hand,foot,and mouth disease (HFMD) in children.Different strains from Gansu were cloned and the P1 protein was sequenced and analysed.Results indicate that there are three kinds of EV71 infections prevalent in Gansu.The VP1 protein from one of these strains,55F,was expressed.The recombinant protein was expressed with high level and reacted specifically with the EV71 patient antibody,the recombinant protein was also applied to raise antiserum in rabbits and after the fourth injection a high titer of antiserum was detected by ELISA assay.These data are useful for further clarification of prevalent EV71 strains in the north of China at the molecular level and provide a basis for EV71 diagnosis.

  14. Expression of enterovirus 71 capsid protein VP1 in Escherichia coli and its clinical application

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    Mei Shi

    2013-12-01

    Full Text Available The VPl gene of enterovirus 71 (EV71 was synthesized, construct a recombinant plasmid pET15b/VP1 and expressed in E. coli BL21. The recombinant VP1 protein could specifically react with EV71-infected patient sera without the cross-reaction with serum antibodies of coxsackievirus A16 (CA16, A4, A5, B3 and B5 as well as echovirus 6. In acute and convalescent phases, IgM and IgG antibodies of 182 serum samples were detected by ELISA with recombinant VP1 protein as a coated antigen. The results showed that the sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV of IgM antibodies in serum samples for the diagnosis of EV71 infection were 90.1, 98.4, 98.8 and 88.7%, respectively; similarly, those of IgG antibodies in serum samples were 82.4, 89.1, 91.5 and 78.1%, respectively. Five of 80 samples (6.25% from CA16infected patients were detected positive by ELISA with recombinant VP1 protein in which indicated the cross reactions and 0 of 5 samples from patients infected with other enteroviruses including CA4, CA5, CB3, CB5 and echovirus 6. Therefore, the recombinant VP1 protein of EV7l may provide a theoretical reference for establishing an effective antibody screening of IgM for EV71-infected patients with clinically suspected hand, foot, and mouth disease (HFMD.

  15. Identification of site-specific adaptations conferring increased neural cell tropism during human enterovirus 71 infection.

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    Samuel Cordey

    Full Text Available Enterovirus 71 (EV71 is one of the most virulent enteroviruses, but the specific molecular features that enhance its ability to disseminate in humans remain unknown. We analyzed the genomic features of EV71 in an immunocompromised host with disseminated disease according to the different sites of infection. Comparison of five full-length genomes sequenced directly from respiratory, gastrointestinal, nervous system, and blood specimens revealed three nucleotide changes that occurred within a five-day period: a non-conservative amino acid change in VP1 located within the BC loop (L97R, a region considered as an immunogenic site and possibly important in poliovirus host adaptation; a conservative amino acid substitution in protein 2B (A38V; and a silent mutation in protein 3D (L175. Infectious clones were constructed using both BrCr (lineage A and the clinical strain (lineage C backgrounds containing either one or both non-synonymous mutations. In vitro cell tropism and competition assays revealed that the VP1₉₇ Leu to Arg substitution within the BC loop conferred a replicative advantage in SH-SY5Y cells of neuroblastoma origin. Interestingly, this mutation was frequently associated in vitro with a second non-conservative mutation (E167G or E167A in the VP1 EF loop in neuroblastoma cells. Comparative models of these EV71 VP1 variants were built to determine how the substitutions might affect VP1 structure and/or interactions with host cells and suggest that, while no significant structural changes were observed, the substitutions may alter interactions with host cell receptors. Taken together, our results show that the VP1 BC loop region of EV71 plays a critical role in cell tropism independent of EV71 lineage and, thus, may have contributed to dissemination and neurotropism in the immunocompromised patient.

  16. Genetic diversity and molecular characterization of enteroviruses from sewage-polluted urban and rural rivers in the Philippines.

    Science.gov (United States)

    Apostol, Lea Necitas G; Imagawa, Tomifumi; Suzuki, Akira; Masago, Yoshifumi; Lupisan, Socorro; Olveda, Remigio; Saito, Mariko; Omura, Tatsuo; Oshitani, Hitoshi

    2012-10-01

    Despite the vast distribution and expansive diversity of enteroviruses reported globally, indicators defining a complete view of the epidemiology of enteroviruses in tropical countries such as the Philippines are yet to be established. Detection of enteroviruses in the environment has been one of the markers of circulating viruses in a community. This study aimed to bridge the gap in the epidemiology of enteroviruses in the Philippines by providing an overview of the occurrence of enteroviruses in both urban and rural rivers. Molecular detection directed at the VP1 region of the enterovirus genome was performed on 44 grab river water samples collected from April to December 2009. The majority of the enterovirus serotypes detected were clustered with human enterovirus C species (HEV-C; 21/42), followed by HEV-B (12/42) and HEV-A (9/42). Porcine enterovirus 9 was also found in 12 out of 44 water samples. Phylogenetic analysis indicated that the viruses detected were closely related, if not all forming a monophyletic clade, with those enteroviruses detected previously from acute flaccid paralysis cases in the country. The clustering of environmental and human enterovirus strains implies that the circulation of these strains were associated with river contamination. This study gives further evidence of the environmental persistence of enteroviruses once they are shed in feces and likewise, provides additional data which may help in understanding the epidemiology of enteroviruses in humans, highlighting the need for more studies on the potential public health risks linked with enteroviruses found in the environment and their eventual clinical consequences in the country.

  17. Development of a sensitive and specific epitope-blocking ELISA for universal detection of antibodies to human enterovirus 71 strains.

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    Fang He

    Full Text Available BACKGROUND: Human Enterovirus 71 (EV71 is a common cause of hand, foot and mouth disease (HFMD in young children. It is often associated with severe neurological diseases and mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no efficient universal antibody test available to detect EV71 infections. METHODOLOGY/PRINCIPAL FINDING: In the present study, an epitope-blocking ELISA was developed to detect specific antibodies to human EV71 viruses in human or animal sera. The assay relies on a novel monoclonal antibody (Mab 1C6 that specifically binds to capsid proteins in whole EV71 viruses without any cross reaction to any EV71 capsid protein expressed alone. The sensitivity and specificity of the epitope-blocking ELISA for EV71 was evaluated and compared to microneutralization using immunized animal sera to multiple virus genotypes of EV71 and coxsackieviruses. Further, 200 serum sample from human individuals who were potentially infected with EV71 viruses were tested in both the blocking ELISA and microneutralization. Results indicated that antibodies to EV71 were readily detected in immunized animals or human sera by the epitope blocking ELISA whereas specimens with antibodies to other enteroviruses yielded negative results. This assay is not only simpler to perform but also shows higher sensitivity and specificity as compared to microneutralization. CONCLUSION: The epitope-blocking ELISA based on a unique Mab 1C6 provided highly sensitive and 100% specific detection of antibodies to human EV71 viruses in human sera.

  18. 肠道病毒71型疫苗研究进展%Research progress of enterovirus 71 vaccines

    Institute of Scientific and Technical Information of China (English)

    袁晓晶; 温红玲; 王志玉

    2012-01-01

    Enterovirus 71 (EV71) is one of the main causative pathogens of hand,foot and mouth disease resulting in neurological complications and death.There are no effective drugs and measures for EV71 infection at present.Development of effective vaccines is the best method to control EV71 epidemic.This review summarizes the research progress of EV71 vaccines.%肠道病毒71型(enterovirus 71,EV71)是引起手足口病(hand,foot and mouth disease,HFMD)的主要病原体之一,HFMD可并发神经系统疾病,甚至导致死亡.对于EV71感染,目前尚无有效的治疗药物和措施,因此研制有效的疫苗是控制EV71流行的最佳方法.此文就EV71疫苗的研究进展进行综述.

  19. Inhibition of enterovirus 71 entry by transcription factor XBP1

    Energy Technology Data Exchange (ETDEWEB)

    Jheng, Jia-Rong; Lin, Chiou-Yan [Department of Biochemistry and Research Center for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa First Road, Kweishan, Taoyuan 333, Taiwan (China); Horng, Jim-Tong, E-mail: jimtong@mail.cgu.edu.tw [Department of Biochemistry and Research Center for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa First Road, Kweishan, Taoyuan 333, Taiwan (China); Lau, Kean Seng [Department of Biochemistry and Research Center for Emerging Viral Infections, Chang Gung University, 259 Wen-Hwa First Road, Kweishan, Taoyuan 333, Taiwan (China)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer IRE1 was activated but no XBP1 splicing was detected during enterovirus 71 infection. Black-Right-Pointing-Pointer XBP1 was subject to translational shutoff by enterovirus 71-induced eIF4G cleavage. Black-Right-Pointing-Pointer The uptake of UV-irradiated virus was decreased in XBP1-overexpressing cells. -- Abstract: Inositol-requiring enzyme 1 (IRE1) plays an important role in the endoplasmic reticulum (ER), or unfolded protein, stress response by activating its downstream transcription factor X-box-binding protein 1 (XBP1). We demonstrated previously that enterovirus 71 (EV71) upregulated XBP1 mRNA levels but did not activate spliced XBP1 (XBP1s) mRNA or its downstream target genes, EDEM and chaperones. In this study, we investigated further this regulatory mechanism and found that IRE1 was phosphorylated and activated after EV71 infection, whereas its downstream XBP1s protein level decreased. We also found that XBP1s was not cleaved directly by 2A{sup pro}, but that cleavage of eukaryotic translation initiation factor 4G by the EV71 2A{sup pro} protein may contribute to the decrease in XBP1s expression. Knockdown of XBP1 increased viral protein expression, and the synthesis of EV71 viral protein and the production of EV71 viral particles were inhibited in XBP1-overexpressing RD cells. When incubated with replication-deficient and UV-irradiated EV71, XBP1-overexpressing RD cells exhibited reduced viral RNA levels, suggesting that the inhibition of XBP1s by viral infection may underlie viral entry, which is required for viral replication. Our findings are the first indication of the ability of XBP1 to inhibit viral entry, possibly via its transcriptional activity in regulating molecules in the endocytic machinery.

  20. Divergent Requirement for a DNA Repair Enzyme during Enterovirus Infections

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    Sonia Maciejewski

    2015-12-01

    Full Text Available Viruses of the Enterovirus genus of picornaviruses, including poliovirus, coxsackievirus B3 (CVB3, and human rhinovirus, commandeer the functions of host cell proteins to aid in the replication of their small viral genomic RNAs during infection. One of these host proteins is a cellular DNA repair enzyme known as 5′ tyrosyl-DNA phosphodiesterase 2 (TDP2. TDP2 was previously demonstrated to mediate the cleavage of a unique covalent linkage between a viral protein (VPg and the 5′ end of picornavirus RNAs. Although VPg is absent from actively translating poliovirus mRNAs, the removal of VPg is not required for the in vitro translation and replication of the RNA. However, TDP2 appears to be excluded from replication and encapsidation sites during peak times of poliovirus infection of HeLa cells, suggesting a role for TDP2 during the viral replication cycle. Using a mouse embryonic fibroblast cell line lacking TDP2, we found that TDP2 is differentially required among enteroviruses. Our single-cycle viral growth analysis shows that CVB3 replication has a greater dependency on TDP2 than does poliovirus or human rhinovirus replication. During infection, CVB3 protein accumulation is undetectable (by Western blot analysis in the absence of TDP2, whereas poliovirus protein accumulation is reduced but still detectable. Using an infectious CVB3 RNA with a reporter, CVB3 RNA could still be replicated in the absence of TDP2 following transfection, albeit at reduced levels. Overall, these results indicate that TDP2 potentiates viral replication during enterovirus infections of cultured cells, making TDP2 a potential target for antiviral development for picornavirus infections.

  1. Viral loads of cerebrospinal fluid in infants with enterovirus meningitis.

    Science.gov (United States)

    Kawashima, Hisashi; Ioi, Hiroaki; Ishii, Chiako; Hasegawa, Yuka; Amaha, Masahiro; Kashiwagi, Yasuyo; Takekuma, Kouji; Hoshika, Akinori; Watanabe, Yasuo

    2008-01-01

    For a better understanding of the role of the viral load, free radicals, and cytokines in viral meningitis, we surveyed cerebrospinal fluid (CSF) obtained from patients below 1 year of age who showed positive for enterovirus. In their first examinations interleukin (IL)-6 and free radicals increased whereas pleocytosis was rarely observed. IL-6 decreased within the short period. Viral loads and free radicals increased simultaneously. IL-6 and free radicals of CSF are helpful for diagnosis and treatment of viral meningitis at an early stage.

  2. Microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse-transcription polymerase chain reaction for the rapid detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens.

    Science.gov (United States)

    Jia, Ruan; Chengjun, Sun; Heng, Chen; Chen, Zhou; Yuanqian, Li; Yongxin, Li

    2015-07-01

    Enterovirus 71 and Coxsackievirus A16 are the main pathogens causing hand-foot-mouth disease. In this paper, microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse transcript-polymerase chain reaction has been developed for the detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens. The specific reverse transcription-polymerase chain reaction amplicons labeled with SYBR Orange were separated by microchip capillary electrophoresis and detected by laser induced fluorescence detector within 7 min. The intraday and interday relative standard deviation of migration time for DNA Marker was in the range of 1.36-2.94 and 2.78-3.96%, respectively. The detection limits were as low as 2.06 × 10(3) copies/mL for Enterovirus 71 and 5 × 10(3) copies/mL for Coxsackievirus A16. No cross-reactivity was observed with rotavirus, astrovirus, norovirus, and adenovirus, which showed good specificity of the method. This assay was validated using 100 throat swab specimens that were detected by real-time reverse-transcript polymerase chain reaction in parallel and the two methods produced the same results. This study provided a rapid, sensitive and specific method for the detection of Enterovirus 71 and Coxsackievirus A16, which make a contribution to significant time and cost saving for the identification and treatment of patients.

  3. The complete genome of Enterovirus 71 China strain

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Five overlapping clones covering the full genome of Enterovirus71 China strain SHZH98 were obtained and then the sequences were determined by the chain termination method. It showed that the full length of EV71 SHZH98 genome (not including Poly A tail) is 7408 bp. There are some diversities on the lengths and sequences of 5′ UTR and 3′ UTR between SHZH98 and the other EV71 strains. In P1 capsid region, which is closely associated with viral immunogenicity, EV71 strain SHZH98 shares the highest homology with Taiwan strains; but in P2 and P3 non-structural gene regions there are higher identities with Coxsakievirus A16 and EV71 strains MS, BrCr than with Taiwan strains. Phylogenetic tree constructed by structural gene region indicates that China strain SHZH98 has a closer relationship with Taiwan strains, however, in the non-coding region it has a closer relationship with Coxsakievirus A16, EV71 strains MS and BrCr. EV71 China strain was analyzed at the molecular level. The results will contribute to the basic study on enteroviruses and the EV71 prevention in China.

  4. Whole Genome Sequencing of Enterovirus species C Isolates by High-throughput Sequencing: Development of Generic Primers

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    Maël Bessaud

    2016-08-01

    Full Text Available Enteroviruses are among the most common viruses infecting humans and can cause diverse clinical syndromes ranging from minor febrile illness to severe and potentially fatal diseases. Enterovirus species C (EV-C consists of more than 20 types, among which the 3 serotypes of polioviruses, the etiological agents of poliomyelitis, are included. Biodiversity and evolution of EV-C genomes are shaped by frequent recombination events. Therefore, identification and characterization of circulating EV-C strains require the sequencing of different genomic regions.A simple method was developed to sequence quickly the entire genome of EV-C isolates. Four overlapping fragments were produced separately by RT-PCR performed with generic primers. The four amplicons were then pooled and purified prior to be sequenced by high-throughput technique.The method was assessed on a panel of EV-Cs belonging to a wide-range of types. It can be used to determine full-length genome sequences through de novo assembly of thousands of reads. It was also able to discriminate reads from closely related viruses in mixtures.By decreasing the workload compared to classical Sanger-based techniques, this method will serve as a precious tool for sequencing large panels of EV-Cs isolated in cell cultures during environmental surveillance or from patients, including vaccine-derived polioviruses.

  5. Seroprevalence of human enterovirus 71 and coxsackievirus A16 in Guangdong, China, in pre- and post-2010 HFMD epidemic period.

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    Wei Li

    Full Text Available BACKGROUND: Human Enterovirus 71 and Coxsackie A16 have caused many outbreaks in the last decade in mainland China, resulting in thousands of fatal cases. Seroepidemiology which provides important information to document population immunity is rare in China. METHODOLOGY/PRINCIPAL FINDINGS: A cross sectional study of Enterovirus 71 (EV71 and Coxsackie A16 (CA16 seroprevalence was carried out in Guangdong, China, pre- and post- the 2010 hand, foot and mouth disease (HFMD epidemic period. The levels of EV71 and CA16 specific antibodies were evaluated by a microneutralization test and the geometric mean titer (GMT was calculated and compared. Our results indicated frequent infection by EV71 and CA16 in Guangdong before the 2010 epidemic. Only EV71 neutralizing antibody but not CA16 seroprevalence was significantly increased after the 2010 HFMD epidemic. Children less than 3 years old especially those aged 2 years showed the lowest positive rates for EV71 and CA16 NA before epidemic and the most significantly increased EV71 seroprevalence after epidemic. CA16 GMT values declined after the 2010 epidemic. CONCLUSIONS: These results indicate EV71 was the major pathogen of HFMD in Guangdong during the 2010 epidemic. The infection occurs largely in children less than 3 years, who should have first priority to receive an EV71 vaccine.

  6. Progress in research of enterovirus 71 vaccines%EV71疫苗研制新进展

    Institute of Scientific and Technical Information of China (English)

    赵蕾; 陈敬贤; 王明丽

    2013-01-01

    肠道病毒71型(enterovirus 71,EV71)是引起手足口病和神经系统并发症的重要病原体.近几年,世界多个地区发生了由EV72感染引起的手足口病.由于目前尚无有效的抗病毒药物对患者进行治疗,因而疫苗的研制成为预防和控制EV71传播的关键.此文主要就近年EV71疫苗的研制进展做一综述.%Enterovirus 71 (EV71) is known to be a causative agent of hand,foot and mouth disease (HFMD) and severe neurological complications.Many outbreaks caused by EV71 have occurred in different regions of the world.Due to lacking an effective antiviral agent,development of effective vaccines has become the top priority in terms of control strategies.This article reviews the recent advancement in the design of various kinds of vaccines against EV71.

  7. Whole Genome Sequencing of Enterovirus species C Isolates by High-Throughput Sequencing: Development of Generic Primers

    Science.gov (United States)

    Bessaud, Maël; Sadeuh-Mba, Serge A.; Joffret, Marie-Line; Razafindratsimandresy, Richter; Polston, Patsy; Volle, Romain; Rakoto-Andrianarivelo, Mala; Blondel, Bruno; Njouom, Richard; Delpeyroux, Francis

    2016-01-01

    Enteroviruses are among the most common viruses infecting humans and can cause diverse clinical syndromes ranging from minor febrile illness to severe and potentially fatal diseases. Enterovirus species C (EV-C) consists of more than 20 types, among which the three serotypes of polioviruses, the etiological agents of poliomyelitis, are included. Biodiversity and evolution of EV-C genomes are shaped by frequent recombination events. Therefore, identification and characterization of circulating EV-C strains require the sequencing of different genomic regions. A simple method was developed to quickly sequence the entire genome of EV-C isolates. Four overlapping fragments were produced separately by RT-PCR performed with generic primers. The four amplicons were then pooled and purified prior to being sequenced by a high-throughput technique. The method was assessed on a panel of EV-Cs belonging to a wide-range of types. It can be used to determine full-length genome sequences through de novo assembly of thousands of reads. It was also able to discriminate reads from closely related viruses in mixtures. By decreasing the workload compared to classical Sanger-based techniques, this method will serve as a precious tool for sequencing large panels of EV-Cs isolated in cell cultures during environmental surveillance or from patients, including vaccine-derived polioviruses. PMID:27617004

  8. A novel universal neutralizing monoclonal antibody against enterovirus 71 that targets the highly conserved "knob" region of VP3 protein.

    Directory of Open Access Journals (Sweden)

    Tanja K Kiener

    Full Text Available Hand, foot and mouth disease caused by enterovirus 71(EV71 leads to the majority of neurological complications and death in young children. While putative inactivated vaccines are only now undergoing clinical trials, no specific treatment options exist yet. Ideally, EV71 specific intravenous immunoglobulins could be developed for targeted treatment of severe cases. To date, only a single universally neutralizing monoclonal antibody against a conserved linear epitope of VP1 has been identified. Other enteroviruses have been shown to possess major conformational neutralizing epitopes on both the VP2 and VP3 capsid proteins. Hence, we attempted to isolate such neutralizing antibodies against conformational epitopes for their potential in the treatment of infection as well as differential diagnosis and vaccine optimization. Here we describe a universal neutralizing monoclonal antibody that recognizes a conserved conformational epitope of EV71 which was mapped using escape mutants. Eight escape mutants from different subgenogroups (A, B2, B4, C2, C4 were rescued; they harbored three essential mutations either at amino acid positions 59, 62 or 67 of the VP3 protein which are all situated in the "knob" region. The escape mutant phenotype could be mimicked by incorporating these mutations into reverse genetically engineered viruses showing that P59L, A62D, A62P and E67D abolish both monoclonal antibody binding and neutralization activity. This is the first conformational neutralization epitope mapped on VP3 for EV71.

  9. The clinical correlation of regulatory T cells and cyclic adenosine monophosphate in enterovirus 71 infection.

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    Shih-Min Wang

    Full Text Available Brainstem encephalitis (BE and pulmonary edema (PE are notable complications of enterovirus 71 (EV71 infection.This study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment.Patients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD or BE group, and the autonomic nervous system (ANS dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP levels, and the regulatory T cell (Tregs profiles of the patients were determined.Patients with ANS dysregulation or PE exhibited significantly low frequency of CD4(+CD25(+Foxp3+ and CD4(+Foxp3(+ T cells compared with patients with HFMD or BE. The expression frequency of CD4-CD8- was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment.These findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels.

  10. A novel dromedary camel enterovirus in the family Picornaviridae from dromedaries in the Middle East.

    Science.gov (United States)

    Woo, Patrick C Y; Lau, Susanna K P; Li, Tong; Jose, Shanty; Yip, Cyril C Y; Huang, Yi; Wong, Emily Y M; Fan, Rachel Y Y; Cai, Jian-Piao; Wernery, Ulrich; Yuen, Kwok-Yung

    2015-07-01

    The recent emergence of Middle East respiratory syndrome coronavirus from the Middle East and the discovery of the virus from dromedary camels have boosted interest in the search for novel viruses in dromedaries. Whilst picornaviruses are known to infect various animals, their existence in dromedaries was unknown. We describe the discovery of a novel picornavirus, dromedary camel enterovirus (DcEV), from dromedaries in Dubai. Among 215 dromedaries, DcEV was detected in faecal samples of four (1.9 %) dromedaries [one (0.5 %) adult dromedary and three (25 %) dromedary calves] by reverse transcription PCR. Analysis of two DcEV genomes showed that DcEV was clustered with other species of the genus Enterovirus and was most closely related to and possessed highest amino acid identities to the species Enterovirus E and Enterovirus F found in cattle. The G+C content of DcEV was 45 mol%, which differed from that of Enterovirus E and Enterovirus F (49-50 mol%) by 4-5 %. Similar to other members of the genus Enterovirus, the 5' UTR of DcEV possessed a putative type I internal ribosome entry site. The low ratios of the number of nonsynonymous substitutions per non-synonymous site to the number of synonymous substitutions per synonymous site (Ka/Ks) of various coding regions suggested that dromedaries are the natural reservoir in which DcEV has been stably evolving. These results suggest that DcEV is a novel species of the genus Enterovirus in the family Picornaviridae. Western blot analysis using recombinant DcEV VP1 polypeptide showed a high seroprevalence of 52 % among serum samples from 172 dromedaries for IgG, concurring with its much higher infection rates in dromedary calves than in adults. Further studies are important to understand the pathogenicity, epidemiology and genetic evolution of DcEV in this unique group of animals.

  11. Genetic Analysis of the VP1 Region of Human Enterovirus 71 Strains Isolated in Fuyang, China, During 2008

    Institute of Scientific and Technical Information of China (English)

    Shao-hui MA; Jian-sheng LIU; Jing-jing WANG; Hai-jing SHI; Hui-juan YANG; Jun-ying CHEN; Long-ding LIU; Qi-han LI

    2009-01-01

    Enterovirus 71 (EV71) is a common cause of Hand, foot, and mouth disease (HFMD) and may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity of EV71, we determined and analyzed the complete VP1 sequences (891 nucleotides) from nine EV71 strains isolated in Fuyang, China. We found that nine EV71 strains isolated were over 98% homologous at the nucleotide level and 93%-100% homologous to members of the C4 subgenogroup. At the amino acid level, these Fuyang strains were 99% -100% homologous to one another, 97%-100% homologous to members of the C4 subgenogroup, and the histidine(H) at amino acid position 22 was conserved among the Fuyang strains. The results indicate that Fuyang isolates belong to genotype C4, and an H at position 22 appears to be a marker for the Fuyang strains.

  12. Enterovirus 71 infection-associated acute flaccid paralysis: a case series of long-term neurologic follow-up.

    Science.gov (United States)

    Lee, Hsiu-Fen; Chi, Ching-Shiang

    2014-10-01

    The authors undertook long-term neurologic outcomes of 27 patients aged 0 to 15 years with enterovirus 71-related acute flaccid paralysis from June 1998 to July 2012. Motor function outcome was graded from class I (complete recovery) to class V (permanent paralytic limbs). Twelve of 20 patients (60%) who received intravenous immunoglobulin for treatment of acute flaccid paralysis had motor function outcomes in classes III to V. The median duration of follow-up was 6 months, during which time 7 of 13 patients (54%) with central nervous system infection, 3 of 6 patients (50%) with autonomic nervous system dysregulation, and 3 of 8 patients (37%) with heart failure showed motor function outcomes in classes III to V. These findings suggested that the usage of intravenous immunoglobulin and the severity of disease staging at disease onset might not be able to predict long-term motor function outcomes.

  13. Effect of Meteorological Conditions and Geographical Factors in the Onset of Enterovirus 71

    Science.gov (United States)

    Chen, Yu-An; Yu, Hwa-Lung

    2015-04-01

    Since it was first recognized in California in 1969, enterovirus 71 (EV71) infection has been a significant cause of neurological disorder and death in children worldwide. In 1998 a historic epidemic of EV71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan. The impact of EV71 infection is greatest during the summer months in Asia, and epidemics recur with a seasonal pattern. It was reported that seasonal patterns of EV71 differed by geographical localities. Previous studies have also showed significant relationships between meteorological variables, in particular, temperature and relative humidity, and the seasonal epidemic patterns of EV71. However, important issues that remain unclear include the spatiotemporal pattern of the EV71 outbreaks in Taiwan, and what role of favorable meteorological conditions in the transmission of the disease in the space-time domain. Thus, this study used a semiparametric generalized additive model (GAM) to understand the association between EV71 and meteorological factors across space and time. This study utilized a population-based database containing space-time data for clinic and hospital visits (i.e., hospital location and appointment times) of EV71 occurring in children less than 18 years old in Taipei from 1998 to 2008. Meteorological data (i.e., temperature, rainfall, and relative humidity) for the study period were provided by the Taiwan Central Weather Bureau. This study expect to find out an important meteorological factor and threshold.

  14. Expression, purification and characterization of enterovirus-71virus-like particles

    Institute of Scientific and Technical Information of China (English)

    Yao-Chi Chung; Jen-Huang Huang; Chia-Wei Lai; Heng-Chun Sheng; Shin-Ru Shih; Mei-Shang Ho; Yu-Chen Hu

    2006-01-01

    AIM: Enterovirus 71 (EV71) has been implicated as the etiological agent responsible for the recent outbreaks of hand, foot and mouth disease associated with severe neurological diseases in the Asia-Pacific region.METHODS: The assembly process was hypothesized to occur via an orchestrated proteolytic processing of the P1 precursor by the viral protease 3CD. To test this hypothesis, we constructed 3 recombinant baculoviruses:Bac-P1 expressing P1; Bac-3CD expressing 3CD; and Bac-P1-3CD co-expressing P1 and 3CD.RESULTS: Both single infection by Bac-P1-3CD and coinfection by Bac-P1 and Bac-3CD resulted in correct cleavage of P1 to yield individual proteins VP0, VP1 and VP3, while the former approach yielded higher VLP production. In the cells, the structural proteins selfassembled into clusters of virus-like particles (VLP)resembling the authentic EV71 particle aggregates.After ultracentrifugation purification, the dispersed VLPs were indistinguishable from the authentic virus in size, appearance, composition and surface epitopes, as determined by SDS-PAGE, Western blot, transmission electron microscopy and immunogold labeling.CONCLUSION: Our data, for the first time, suggest that in insect cells EV71 structural proteins adopt a processing and assembly pathway similar to poliovirus assembly. The preservation of particle morphology and composition suggest that the VLP may be a valuable vaccine candidate to prevent EV71 epidemics.

  15. Risk Factors for Enterovirus A71 Seropositivity in Rural Indigenous Populations in West Malaysia.

    Science.gov (United States)

    NikNadia, Nmn; Sam, I-Ching; Khaidir, Nasibah; Ngui, Romano; Lim, Yvonne A L; Goh, Xiang Ting; Choy, Seow Huey; Chan, Yoke Fun

    2016-01-01

    Enterovirus A71 (EV-A71), which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. In Malaysia, the indigenous rural community (Orang Asli) has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. This cross-sectional study compared the seroepidemiology of EV-A71 among rural Orang Asli and urban Kuala Lumpur populations in West Malaysia, and determined the risk factors associated with EV-A71 seropositivity in rural Orang Asli. Seropositive rates were determined by neutralization assay. EV-A71 seropositivity was strongly associated with increasing age in both populations. Rural Orang Asli children ≤12 years had significantly higher EV-A71 seropositivity rates than urban Kuala Lumpur children (95.5% vs 57.6%, P population. Supply of clean drinking water may reduce the risk of EV-A71 infection. With significantly higher EV-A71 seropositive rates, younger rural children should be a priority target for future vaccination programs in Malaysia.

  16. [Rapid enterovirus genotyping in cerebrospinal fluids: a two-year prospective study in a virology laboratory setting].

    Science.gov (United States)

    Mirand, A; Bailly, J-L; Henquell, C; Peigue-Lafeuille, H

    2008-01-01

    Enterovirus (EV - 68 serotypes) infections comprise a wide spectrum of clinical presentations including infections of the central nervous system. In severe clinical presentation or epidemics, the precise identification of the involved serotype is necessary. To perform enterovirus genotyping directly in cerebrospinal fluid (CSF) samples, and to assess its feasibility in a laboratory setting. Enterovirus genotyping was carried out directly with CSF specimens tested for the diagnostic procedure by amplifying the complete 1D gene encoding the VP1 protein of the HEV-B serotypes (the most frequent) - providing results in two days. Secondly, sequences 1A/1B encoding the VP4/VP2 capsid proteins, respectively, were analysed (results in five days). Direct enterovirus genotyping allowed the identification of enterovirus involved in 77 out of 81 (95%) meningitis cases between January 2006 and December 2007. In combination with the indirect genotyping of enterovirus isolates, identification of the type was achieved in 94 out of 97 (96.9%) patients included in the study. The most frequent serotypes were echovirus 6 (E6) and 13 in 2006, coxsackievirus B2 and E30 in 2007. Four children presented an EV71 associated meningitis. When prospectively applied in a laboratory setting, direct enterovirus genotyping in CSF samples allows the identification of the involved enterovirus in two to five days. This time frame is relevant for an optimal patient management, the rapid identification of a new enterovirus variant or in the context of an epidemic alert.

  17. The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2015-08-01

    Full Text Available 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 baicalin treatment at early stages of EV71 infection. In addition, baicalin could decrease the expressions of FasL and caspase-3, as well as inhibit the apoptosis of EV71-infected human embryonal rhabdomyosarcoma (RD cells. Altogether, these results indicate that baicalin exhibits potent antiviral effect on EV71 infection, probably through inhibiting EV71/3D polymerase expression and Fas/FasL signaling pathways.

  18. A mouse model of paralytic myelitis caused by enterovirus D68.

    Directory of Open Access Journals (Sweden)

    Alison M Hixon

    2017-02-01

    Full Text Available In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68 respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch's postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.

  19. Clinical analysis and follow-up of patients with hand, foot and mouth disease complicated with nervous system damage resulted from enterovirus 71 infection%肠道病毒71型手足口病并发神经系统损害的临床特征及随访研究

    Institute of Scientific and Technical Information of China (English)

    陈峰; 李建军; 刘涛; 文国强; 李岩; 向伟

    2012-01-01

    Objective To explore the imaging characterization and clinical follow-up of neurological complications associated with the enterovirus 71 ( EV71 ) epidemics in 12 children with hand, foot and mouth disease ( HFMD). Methods Total of 12 HFMD cases with neurological complications during the recent EV71 outbreaks in Hainan, from May 2008 to October 2011 were collected and analyzed, retrospectively. The recovery of their impairment was followed up at the 4th weekend, 3 to 6 months, and 3 cases were followed-up for 1 year. Results In brainstem encephalitis ( 6 cases ), all lesions presented as significant hyperintense in the posterior portions of the medulla oblongata, midbrain, and pons as seen in T2-weighted images and hypointense in Tl-weighted images. In sagittal sections, acute flaccid paralysis( AFP) associated with HFMD ( 4 cases ) due to EV71 infection appeared as a linear high signal of the posterior in the spinal cord. Two symmetrical, well-defined hyperintense lesions in the spinal cord were found in T2-weighted transverse images, strong enhancement of the ventral horns and root were found in the contrast-enhanced axial Tl-weighted image. The manifestations of aseptic meningitis ( AM ) ( 2 cases ) on MRI with widening of the interhe mi spheric and hydrocephalus could be the indirect signs of AM. MRI and clinics of the 2 cases with AM were normal in the 4 weeks follow-up. The patients with single pons lesions recovered better than those with multi-lesions, also patients with simple brainstem encephalitis recovered better than those complicated with AFP cases. The patients with single extremity recovered faster than those with paralysis of both or four limbs, some lesions in the lower thoracic cord and conus recovered faster than those with cervical cord in the follow-up. Conclusions MRI is an effective method to investgate neurological complications associated with EV71 epidemics. Involvements of posterior portions of the medulla oblongata and pons, and

  20. The long-term follow-up of children with hand-foot-mouth disease complicated with brainstem encephalitis caused by enterovirus 71%肠道病毒71型手足口病合并脑干脑炎患儿的远期随访

    Institute of Scientific and Technical Information of China (English)

    陈冉冉; 何颜霞; 曾洪武; 曾伟彬; 陈敏

    2015-01-01

    目的:研究肠道病毒71(EV71)型手足口病(HFMD)合并脑干脑炎患儿的远期预后。方法对2010年1月至2012年12月在深圳市儿童医院住院的82例EV71型HFMD合并脑干脑炎患儿进行随访。随访包括电话问卷调查、神经系统查体、智力测试和头颅磁共振成像(MRI)复查。结果1.电话随访82例患儿中,遗留后遗症者14例(17%,14/82例),包括肢体无力5例、性格改变3例、肢体抖动1例、癫1例、抽搐1例、睡眠呼吸障碍并吞咽障碍1例、发声低弱并吞咽障碍1例、中枢性低通气并吞咽障碍1例,且临床严重程度越重的患儿遗留后遗症概率越大,差异有统计学意义(χ2=27.273,P0.05)。3.头颅MRI复查28例,MRI仍显示脑干异常信号6例,包括原病灶吸收变小、软化、胶质增生等。6例MRI异常患儿中,遗留后遗症者占83%(5/6例)。结论 EV71型HFMD合并脑干脑炎患儿后遗症主要为肢体运动及脑神经障碍,其后遗症概率与临床严重程度呈正比。大多数患儿的认知功能预后良好,远期头颅MRI仍显示脑干病灶者,存在神经系统后遗症或边缘智力概率较大。%Objective To study the long-term prognosis of hand-foot-mouth disease( HFMD) complicated with brainstem encephalitis caused by enterovirus 71(EV71) . Methods Long-term follow-up of 82 cases of EV71 HFMD complicated with brainstem encephalitis were conducted,who were hospitalized in Shenzhen Children′s Hospital from January to December of 2012. Follow-up methods included telephone interview,neurological examination,intelli-gence tests and brain magnetic resonance imaging (MRI) study. Results (1)Telephone interview and physical exam results indicated that 14 of 82 cases (17%) had sequelae,including limb weakness in 5 cases,personality changes in 3 cases,limb shaking in 1 case, epilepsy in 1 case,seizures in 1 case,sleep-disordered breathing and swallowing disorder in 1 case,low voice and swallowing disorder in 1 case

  1. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Directory of Open Access Journals (Sweden)

    Shane C McAllister

    Full Text Available Enterovirus D68 (EV-D68 is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3% were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA compared to HRV (129.7 nA. Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  2. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Science.gov (United States)

    McAllister, Shane C; Schleiss, Mark R; Arbefeville, Sophie; Steiner, Marie E; Hanson, Ryan S; Pollock, Catherine; Ferrieri, Patricia

    2015-01-01

    Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  3. Disease: H01327 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available often accompanied by fever, sore throat, and pain on swallowing. Infectious disease Human enterovirus A [VG...erovirus 71 in Taiwan, 1998-2005. Pediatrics 120:e244-52 (2007) ... ... Wang ST, Cheng YT, Yang JY Epidemiologic features of hand-foot-mouth disease and herpangina caused by ent

  4. Prevalencia de enterovirus en recién nacidos y lactantes que consultaron a un centro de atención de primer nivel, Armenia, Colombia, 2009

    Directory of Open Access Journals (Sweden)

    María Mercedes González

    2011-06-01

    Conclusiones. La circulación de enterovirus en la población infantil estudiada fue de 13,3 % y los serotipos de enterovirus aislados corresponden con los serotipos de mayor prevalencia global. Los resultados obtenidos indican la factibilidad de emplear la RT-N-PCR como herramienta para vigilar la circulación de enterovirus en muestras de heces.

  5. Upper aerodigestive tract sequelae in severe enterovirus 71 infection: predictors and outcome.

    Science.gov (United States)

    Tsou, Yung-An; Cheng, Yuan-Kai; Chung, Hsiung-Kwan; Yeh, Yi-Chun; Lin, Chia-Der; Tsai, Ming-Hsui; Chang, Jeng-Sheng

    2008-01-01

    Enterovirus 71 (EV71) infection sequelae can be severe and life-threatening, and long-term follow-up outcomes remain unknown. Therefore, we conducted a retrospective follow-up study to review airway and neurological sequelae development in patients with severe EV71 infection. We also studied the incidence and risk factors for tracheotomy and gastrostomy requirement. We investigated 202 EV71-infected children according to their disease stage. Seventy-two of them were diagnosed to have EV71 encephalitis, which was characterized by myoclonus, ataxia, nystagmus, oculomotor palsy and bulbar palsy or combinations of these conditions. All the 72 patients required endotracheal intubation due to respiratory failure or ventilator dependence; among these, 14 underwent tracheostomy and 10 underwent gastrostomy. All patients were followed-up for at least 3 years after discharge. Predictors of tracheostomy and gastrostomy requirement were age predictors were age predictors of tracheostomy requirement and pulmonary edema as the significant risk factor for gastrostomy. Long-term neuropsychological impact was observed on children who present the signs of the pulmonary edema or hypotension in the early onset of the EV71 infection. EV71-infected patients who develop neurological pulmonary edema or hypotension should be hemodynamically stabilized and undergo early tracheostomy to prevent further complications. This may improve the decannulation success rate after the brainstem function recovers.

  6. Antiviral Ability of Kalanchoe gracilis Leaf Extract against Enterovirus 71 and Coxsackievirus A16

    Directory of Open Access Journals (Sweden)

    Ching-Ying Wang

    2012-01-01

    Full Text Available Pandemic infection or reemergence of Enterovirus 71 (EV71 and coxsackievirus A16 (CVA16 occurs in tropical and subtropical regions, being associated with hand-foot-and-mouth disease, herpangina, aseptic meningitis, brain stem encephalitis, pulmonary edema, and paralysis. However, effective therapeutic drugs against EV71 and CVA16 are rare. Kalanchoe gracilis (L. DC is used for the treatment of injuries, pain, and inflammation. This study investigated antiviral effects of K. gracilis leaf extract on EV71 and CVA16 replications. HPLC analysis with a C-18 reverse phase column showed fingerprint profiles of K. gracilis leaf extract had 15 chromatographic peaks. UV/vis absorption spectra revealed peaks 5, 12, and 15 as ferulic acid, quercetin, and kaempferol, respectively. K. gracilis leaf extract showed little cytotoxicity, but exhibited concentration-dependent antiviral activities including cytopathic effect, plaque, and virus yield reductions. K. gracilis leaf extract was shown to be more potent in antiviral activity than ferulic acid, quercetin, and kaempferol, significantly inhibiting in vitro replication of EV71 (IC50=35.88 μg/mL and CVA16 (IC50=42.91 μg/mL. Moreover, K. gracilis leaf extract is a safe antienteroviral agent with the inactivation of viral 2A protease and reduction of IL-6 and RANTES expressions.

  7. Molecular epidemiology and evolution of worldwide enterovirus 71 strains isolated from 1970 to 2004

    Institute of Scientific and Technical Information of China (English)

    DONG XiaoNan; YING Jian; CHEN YingHua

    2007-01-01

    Human enterovirus 71 (EV71) is one of the major etiological agents of the hand-foot-and-mouth disease (HFMD) that often causes severe neurological complications. Recently, its outbreaks mainly take place in the torrid zone of the Asia-Pacific region. To study the evolution and genetic variability, we collected 532 EV71 strains with almost complete or complete VP1 sequences (891 nt) isolated worldwide from 1970 to 2004. The pairwise homologies and genetic distances were analyzed. Most strains belong to previously identified genotype B and C. However, a unique strain R13223-IND-01 appears not to fall into current three genotypes (A, B and C), and probably represents a new genotype D. Some orphan strains were observed in the genotypes B and C, and their significance in the EV71 evolution was discussed.Moreover, there is a significant co-variance of 6 discrete positions on VP1 (amino acid 43, 58, 164, 184,240 and 249). This high co-variability is tightly related with the subgenotypes.

  8. Advances in Enterovirus 71 Receptors%EV71的受体研究进展

    Institute of Scientific and Technical Information of China (English)

    徐广振; 李明; 李晋涛

    2011-01-01

    @@ 手足口病(Hand-foot-mouth disease,HFMD)是一种临床表现为手、足、口腔等部位的疱疹及中枢神经系统并发症的婴幼儿疾病,其病原体以柯萨奇病毒A16型(Coxsackievirus A16,CoxA16)和人肠道病毒71型(Human enterovirus 71,EV71)最为常见[1].2008年中国卫生部将HFMD列人丙类传染病目录.近年来,引起手足口病的主要病原体为小RNA病毒科肠道病毒71型[2].自1969年EV71在美国加利福尼亚州手足口病疫情中首次报道后,该病毒已在世界范围内引起十余次手足口病暴发和流行,且死亡病例趋于增多[3].仅1998年中国台湾EV71大暴发中就出现129 000例病例,其中重症病例多达400个,死亡78例[4].

  9. Expression and Purification of Enterovirus Type 71 Polyprotein P1 using Pichia pastoris system

    Institute of Scientific and Technical Information of China (English)

    Xue Han; Xiaoling Ying; Hao Huang; Shili Zhou; Qi Huang

    2012-01-01

    Enterovirus type 71(EV71) causes severe hand-foot-and-mouth disease(HFMD) resulting in hundreds of deaths of children every year; However,currently,there is no effective treatment for EV71.In this study,the EV71 poly-protein(EV71-P1 protein) gene was processed and cloned into the eukaryotic expression vector pPIC9k and then expressed in Pichia pastoris strain GS115.The EV71 P1 pretein with a molecular weight of 100 kD was produced and secreted into the medium.The soluble EV71 P1 protein was purified by column chromatography with a recovery efficiency of 70%.The result of the immunological analysis showed that the EV71 P1 protein had excellent immunogenicity and could stimulate the production of EV71-VP1 IgG antibody in injected rabbits.We suggest that EV71-P1 protein is an ideal candidate for an EV71 vaccine to prevent EV71 infection.

  10. Cerebrospinal fluid Th1/Th2 cytokine profiles in children with enterovirus 71-associated meningoencephalitis.

    Science.gov (United States)

    Li, Huajun; Li, Shuxian; Zheng, Jianfeng; Cai, Chunyan; Ye, Bin; Yang, Jun; Chen, Zhimin

    2015-03-01

    Enterovirus 71 (EV71) infection can cause severe neurological complications including meningoencephalitis (ME) in some patients with hand, foot and mouth disease (HFMD). However, to date no studies have reported changes in cytokine concentrations and their correlations with clinical variables in patients with ME following EV71 infection. In this study, responses of Th1/Th2 cytokine, including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ, in cerebrospinal fluid (CSF) from patients with EV71-related HFMD with ME and patients with febrile convulsions (FC) were analyzed using cytometric bead array technology. It was found that CSF IL-6 and IFN-γ concentrations were significantly higher in patients with EV71-related ME than in those with FC. Additionally, both CSF IL-6 and IFN-γ concentrations were correlated with CSF cytology, fever duration and duration of hospital stay. More interestingly, a positive correlation between CSF IL-6 and IFN-γ concentrations was observed. Finally, receiver operating characteristic analysis revealed that when a cutoff value of 9.40 pg/mL was set for IL-6, the sensitivity and specificity were 84.5% and 85.5%, respectively, for discriminating EV71-related ME from FC. In conclusion, IL-6 and IFN-γ may be associated with EV71-induced neuropathology. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  11. Genetic diversity and C2-like subgenogroup strains of enterovirus 71, Taiwan, 2008

    Directory of Open Access Journals (Sweden)

    Yang Jyh-Yuan

    2010-10-01

    Full Text Available Abstract Background Human enterovirus 71 (EV-71 is known of having caused numerous outbreaks of hand-foot-mouth disease, and other clinical manifestations globally. In 2008, 989 EV-71 strains were isolated in Taiwan. Results In this study, the genetic and antigenic properties of these strains were analyzed and the genetic diversity of EV-71 subgenogroups surfacing in Taiwan was depicted, which includes 3 previously reported subgenogroups of C5, B5, and C4, and one C2-like subgenogroup. Based on the phylogenetic analyses using their complete genome nucleotide sequences and neutralization tests, the C2-like subgenogroup forms a genetically distinct cluster from other subgenogroups, and the antisera show a maximum of 128-fold decrease of neutralization titer against this subgenogroup. In addition, the subgenogroup C4 isolates of 2008 were found quite similar genetically to the Chinese strains that caused outbreaks in recent years and thus they should be carefully watched. Conclusions Other than to be the first report describing the existence of C2-like subgenogroup of EV-71 in Taiwan, this article also foresees a potential of subgenogroup C4 outbreaks in Taiwan in the near future.

  12. Prevalence of rotavirus, adenovirus, hepatitis A virus and enterovirus in water samples collected from different region of Peshawar, Pakistan.

    Science.gov (United States)

    Ahmad, Tahir; Arshad, Najma; Adnan, Fazal; Sadaf Zaidi, Najam-Us-Sahar; Shahid, Muhammad Talha; Zahoor, Usman; Afzal, Muhammad S; Anjum, Sadia

    2016-12-23

    Viral gastroenteritis and other water-borne diseases are the most neglected areas of research in Pakistan. To determine the quality of water, 4 enteric viruses were studied from different localities of Peshawar, Pakistan. The study validates the viral detection method for Rotavirus (RV), Human adenovirus (HAdV), Enterovirus (EV) and Hepatitis A virus (HAV), directly from water sources of rural areas of Peshawar, KPK, Pakistan. Overall, 95 five water samples were tested; among them, 9.47% were positive for RV, 38.94% for HAdV, 48.42% for EV and 12.63% for HAV. The presence of these viruses in water was directly correlated with meteorological data. High prevalence of EV and HAdV was detected frequently in the wet season from May - September, which can be the potential cause of spreading of gastroenteritis in the population. Environmental surveillance is an additional tool to evaluate the epidemiology of enteric viruses circulating in a given community.

  13. A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIβ

    NARCIS (Netherlands)

    van der Schaar, H.M.; Leyssen, Pieter; Thibaut, H.J.; de Palma, Armando; van der Linden, Lonneke; Lanke, Kjerstin H.W.; Lacroix, Céline; Verbeken, Erik; Conrath, Katja; Macleod, Angus M; Mitchell, Dale R; Palmer, Nicholas J; van de Poël, Hervé; Andrews, Martin; Neyts, Johan; van Kuppeveld, F.J.M.

    2013-01-01

    Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidaz

  14. Epidemiologic and Virologic Investigation of Hand, Foot, and Mouth Disease, Southern Vietnam, 2005

    OpenAIRE

    Van Tu, Phan; Thao, Nguyen Thi Thanh; Perera, David; Truong, Khanh Huu; Tien, Nguyen Thi Kim; Thuong, Tang Chi; How, Ooi Mong; Cardosa, Mary Jane; McMinn, Peter Charles

    2007-01-01

    During 2005, 764 children were brought to a large children’s hospital in Ho Chi Minh City, Vietnam, with a diagnosis of hand, foot, and mouth disease. All enrolled children had specimens (vesicle fluid, stool, throat swab) collected for enterovirus isolation by cell culture. An enterovirus was isolated from 411 (53.8%) of the specimens: 173 (42.1%) isolates were identified as human enterovirus 71 (HEV71) and 214 (52.1%) as coxsackievirus A16. Of the identified HEV71 infections, 51 (29.5%) wer...

  15. Tyrosine sulfation of the amino terminus of PSGL-1 is critical for enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Yorihiro Nishimura

    Full Text Available Enterovirus 71 (EV71 is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1 as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1-P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1-EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1-selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1-EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes.

  16. Tyrosine sulfation of the amino terminus of PSGL-1 is critical for enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Yorihiro Nishimura

    Full Text Available Enterovirus 71 (EV71 is one of the major causative agents of hand, foot, and mouth disease, a common febrile disease in children; however, EV71 has been also associated with various neurological diseases including fatal cases in large EV71 outbreaks particularly in the Asia Pacific region. Recently we identified human P-selectin glycoprotein ligand-1 (PSGL-1 as a cellular receptor for entry and replication of EV71 in leukocytes. PSGL-1 is a sialomucin expressed on the surface of leukocytes, serves as a high affinity counterreceptor for selectins, and mediates leukocyte rolling on the endothelium. The PSGL-1-P-selectin interaction requires sulfation of at least one of three clustered tyrosines and an adjacent O-glycan expressing sialyl Lewis x in an N-terminal region of PSGL-1. To elucidate the molecular basis of the PSGL-1-EV71 interaction, we generated a series of PSGL-1 mutants and identified the post-translational modifications that are critical for binding of PSGL-1 to EV71. We expressed the PSGL-1 mutants in 293T cells and the transfected cells were assayed for their abilities to bind to EV71 by flow cytometry. We found that O-glycosylation on T57, which is critical for PSGL-1-selectin interaction, is not necessary for PSGL-1 binding to EV71. On the other hand, site-directed mutagenesis at one or more potential tyrosine sulfation sites in the N-terminal region of PSGL-1 significantly impaired PSGL-1 binding to EV71. Furthermore, an inhibitor of sulfation, sodium chlorate, blocked the PSGL-1-EV71 interaction and inhibited PSGL-1-mediated viral replication of EV71 in Jurkat T cells in a dose-dependent manner. Thus, the results presented in this study reveal that tyrosine sulfation, but not O-glycosylation, in the N-terminal region of PSGL-1 may facilitate virus entry and replication of EV71 in leukocytes.

  17. Current status of seroepidemiological analysis of enterovirus 71 infection%肠道病毒71型感染的血清流行病学分析近况

    Institute of Scientific and Technical Information of China (English)

    郭磊; 李琦涵

    2012-01-01

    近年来肠道病毒71型(enterovirus 71,EV71)在我国引发了手足口病的暴发和流行.针对该病毒的流行病学研究,可为预防和控制EV71引发的手足口病流行提供重要依据.此文就目前EV71在人群中的血清阳性率和中和抗体水平资料进行综述.%In recent years,the outbreaks of hand,foot and mouth disease (HFMD) caused by enterovirus 71 ( EV71 ) have occurred in China.The epidemiological research of EV71 is an important basis for prevention and control of HFMD caused by EV71.This article reviews the seroprevalence and level of neutralizing antibody against EV71 in population.

  18. Incidence rates of enterovirus 71 infections in young children during a nationwide epidemic in Taiwan, 2008-09.

    Directory of Open Access Journals (Sweden)

    Min-Shi Lee

    Full Text Available OBJECTIVE: Enterovirus 71 (EV71 is causing life-threatening outbreaks in tropical Asia. In Taiwan and other tropical Asian countries, although nationwide EV71 epidemics occur cyclically, age-specific incidence rates of EV71 infections that are critical to estimate disease burden and design vaccine trials are not clear. A nationwide EV71 epidemic occurred in 2008-09 in Taiwan, which provided a unique opportunity to estimate age-specific incidence rates of EV71 infections. STUDY DESIGN: We prospectively recruited 749 healthy neonates and conducted follow-ups from June 2006 to December 2009. Sera were obtained from participants at 0, 6, 12, 24, and 36 months of age for measuring EV71 neutralizing antibody titers. If the participants developed suspected enterovirus illnesses, throat swabs were collected for virus isolation. RESULTS: We detected 28 EV71 infections including 20 symptomatic and 8 asymptomatic infections. Age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0-6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7-12, 13-24, and 25-36 months of age, respectively. Cumulative incidence rate was 15.15 per 100 persons by 36 months of age, respectively. CONCLUSIONS: Risk of EV71 infections in Taiwan increased after 6 months of age during EV71 epidemics. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children.

  19. Progress in Research of Enterovirus Type 71%肠道病毒71型的研究进展

    Institute of Scientific and Technical Information of China (English)

    周世力; 杨帆; 金奇

    2003-01-01

    @@ 肠道病毒71型(enterovirus71,EV71)是小RNA病毒科(Picornaviridae)肠道病毒属(Enterovirus)成员,其感染主要引起患者手足口病(hand-foot-and-mouth disease,HFMD).通常情况下,EV71感染引起的HFMD在临床症状等方面与柯萨奇病毒A16(Coxsackie A16,CA16)引起的手足口病难以区别,但EV71感染除了引起HFMD以外,还能够引起无菌性脑膜炎(aseptic meningitis)、脑干脑炎(brainstem encephalitis)和脊髓灰质炎样的麻痹(poliomyelitis-like paralysis)等多种与神经系统相关的疾病[1].自1974年首次报道[2]以来,EV71已在世界范围内引起十多次爆发与流行[3-6].近年来,EV71病毒的流行在亚太地区呈上升趋势[7-9].根据病毒衣壳蛋白VP1核苷酸序列的差异,可将EV71分为A、B、C 3个基因型,其中,B型和C型又进一步分为B1、B2、B3、B4以及C1和C2亚型[10-12].

  20. Molecular Evolution of Enterovirus 68 Detected in the Philippines

    Science.gov (United States)

    Imamura, Tadatsugu; Suzuki, Akira; Lupisan, Socorro; Okamoto, Michiko; Aniceto, Rapunzel; Egos, Rutchie J.; Daya, Edgardo E.; Tamaki, Raita; Saito, Mariko; Fuji, Naoko; Roy, Chandra Nath; Opinion, Jaime M.; Santo, Arlene V.; Macalalad, Noel G.; Tandoc, Amado; Sombrero, Lydia; Olveda, Remigio; Oshitani, Hitoshi

    2013-01-01

    Background Detection of Enterovirus 68 (EV68) has recently been increased. However, underlying evolutionary mechanism of this increasing trend is not fully understood. Methods Nasopharyngeal swabs were collected from 5,240 patients with acute respiratory infections in the Philippines from June 2009 to December 2011. EV68 was detected by polymerase chain reaction (PCR) targeting for 5′ untranslated region (5′UTR), viral protein 1 (VP1), and VP4/VP2. Phylogenetic trees were generated using the obtained sequences. Results Of the 5,240 tested samples, 12 EV68 positive cases were detected between August and December in 2011 (detection rate, 0.23%). The detection rate was higher among inpatients than outpatients (p<0.0001). Among VP1 sequences detected from 7 patients in 2011, 5 in lineage 2 were diverged from those detected in the Philippines in 2008, however, 2 in lineage 3 were not diverged from strains detected in the Philippines in 2008 but closely associated with strains detected in the United States. Combined with our previous report, EV68 occurrences were observed twice in the Philippines within the last four years. Conclusions EV68 detections might be occurring in cyclic patterns, and viruses might have been maintained in the community while some strains might have been newly introduced. PMID:24073203

  1. Enterovirus 71 virion-associated galectin-1 facilitates viral replication and stability.

    Directory of Open Access Journals (Sweden)

    Pei-Huan Lee

    Full Text Available Enterovirus 71 (EV71 infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children's health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells. Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection.

  2. Risk Factors for Enterovirus A71 Seropositivity in Rural Indigenous Populations in West Malaysia.

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    Nmn NikNadia

    Full Text Available Enterovirus A71 (EV-A71, which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. In Malaysia, the indigenous rural community (Orang Asli has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. This cross-sectional study compared the seroepidemiology of EV-A71 among rural Orang Asli and urban Kuala Lumpur populations in West Malaysia, and determined the risk factors associated with EV-A71 seropositivity in rural Orang Asli. Seropositive rates were determined by neutralization assay. EV-A71 seropositivity was strongly associated with increasing age in both populations. Rural Orang Asli children ≤12 years had significantly higher EV-A71 seropositivity rates than urban Kuala Lumpur children (95.5% vs 57.6%, P < 0.001, and also higher rates in the age groups of 1-3, 4-6 and 7-12 years. Multivariate analysis confirmed that age ≤12 years (adjusted OR 8.1, 95% CI 3.2-20.7, P < 0.001 and using untreated water (adjusted OR 6.2, 95% CI 2.3-16.6, P < 0.001 were independently associated with EV-A71 seropositivity in the Orang Asli population. Supply of clean drinking water may reduce the risk of EV-A71 infection. With significantly higher EV-A71 seropositive rates, younger rural children should be a priority target for future vaccination programs in Malaysia.

  3. Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Seonah; Suh, Sang-Il; Ha, Su Min; Seol, Hae-Young [Korea University Guro Hospital, Korea University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Byeon, Jung Hye; Eun, Baik-Lin [Korea University Guro Hospital, Korea University College of Medicine, Department of Pediatrics, Seoul (Korea, Republic of); Lee, Young Hen; Seo, Hyung Suk [Korea University Ansan Hospital, Korea University College of Medicine, Department of Radiology, Ansan (Korea, Republic of); Eun, So-Hee [Korea University Ansan Hospital, Korea University College of Medicine, Department of Pediatrics, Ansan (Korea, Republic of)

    2012-03-15

    Most enterovirus (EV) 71 infections manifest as mild cases of hand-foot-mouth disease (HFMD)/herpangina with seasonal variations, having peak incidence during the summer. Meanwhile, EV 71 may involve the central nervous system (CNS), causing severe neurologic disease. In many cases, enteroviral encephalomyelitis involves the central midbrain, posterior portion of the medulla oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral roots of the cervical spinal cord, and the lesions show hyperintensity on T2-weighted and fluid-attenuation inversion recovery (FLAIR) images. Our goal was to review usual and unusual magnetic resonance (MR) findings in CNS involvement of enteroviral infection. Among consecutive patients who had HFMD and clinically suspected encephalitis or myelitis and who underwent brain or spinal MR imaging, five patients revealed abnormal MR findings. Diffusion-weighted and conventional MR and follow-up MR images were obtained. From cerebrospinal fluid, stool, or nasopharyngeal swabs, EV 71 was confirmed in all patients. MR imaging studies of two patients showed hyperintensity in the posterior portion of the brainstem on T2-weighted and FLAIR images, which is the well-known MR finding of EV 71 encephalitis. The remaining three cases revealed unusual manifestations: leptomeningeal enhancement, abnormal enhancement along the ventral roots at the conus medullaris level without brain involvement, and hyperintensity in the left hippocampus on T2/FLAIR images. EV 71 encephalomyelitis shows relatively characteristic MR findings; therefore, imaging can be helpful in radiologic diagnosis. However, physicians should also be aware of unusual radiologic manifestations of EV 71. (orig.)

  4. Evaluation of the enterovirus laboratory surveillance system in Denmark, 2010 to 2013

    DEFF Research Database (Denmark)

    Condell, Orla; Midgley, Sofie E; Christiansen, Claus Bohn;

    2016-01-01

    The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus-transmission......The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus...

  5. Genetic and antigenic characterization of enterovirus 71 in Ho Chi Minh City, Vietnam, 2011.

    Directory of Open Access Journals (Sweden)

    Le Phan Kim Thoa

    Full Text Available Enterovirus 71 (EV71 frequently causes fatal infections in young children in Asia. In 2011, EV71 epidemics occurred in southern Vietnam. We conducted genetic and antigenic analysis of the EV71 isolates and found that 94% of them were genotype C4a related to two lineages circulating in China and 6% were genotype C5 which have circulated in Vietnam since 2003. Antigenic variants were not detected. EV71 vaccines are being developed. Longitudinal enterovirus surveillance data are critical to formulate vaccination policy in Vietnam.

  6. Progress in Research on Enterovirus 71 Vaccine%肠道病毒71型疫苗的研发现状及进展

    Institute of Scientific and Technical Information of China (English)

    姚昕; 毛群颖

    2011-01-01

    Hand foot mouth disease (HFMD) has been epidemic in China in recent years. Severe and fatal cases caused by enterovirus 71 (EV71) has become the serious public healthy problem. The only effective measure to control HFMD is developing EV71 vaccine. At present, the vaccine is in developing in several manufacturers in China. This review attempts to give an overview of the necessity, feasibility as well as problem and progress in development of EV71 vaccine.%近年来,手足口病(Hand foot mouth disease,HFMD)在我国呈持续流行态势.其中,肠道病毒71型(Enterovirus 71,EV71)感染引起的严重和死亡病例已成为政府和社会高度关注的公共卫生问题.研发疫苗是控制该病流行的唯一有效措施.目前,我国已有多个单位开展了EV71疫苗的研发工作,本文就EV71疫苗研发的必要性、可行性、研发的难点及研发进展作一综述.

  7. 肠道病毒71型致病机制研究进展%Advances in the research of pathogenesis of enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    鲁卫卫; 郭会杰

    2013-01-01

    Enterovirus 71 (EV71) is one of the major pathogens of hand,foot and mouth disease,which can cause a variety of nervous system-related diseases with high disability and mortality rates.This review summarizes the recent research progress of the immune responses against EV71 and pathogenesis of EV71 infection.%肠道病毒71型(enterovirus 71,EV71)是引起手足口病的主要病原体之一,其感染可导致多种与神经系统相关的疾病,致残率及病死率较高.目前,关于其免疫机制和致病机制尚未完全清楚.此文阐述了机体对EV71的免疫应答以及EV71感染的致病机制的最新研究进展.

  8. Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

    Science.gov (United States)

    Ye, Xiaohua; Fan, Chen; Ku, Zhiqiang; Zuo, Teng; Kong, Liangliang; Zhang, Chao; Shi, Jinping; Liu, Qingwei; Chen, Tan; Zhang, Yingyi; Jiang, Wen; Zhang, Linqi; Huang, Zhong; Cong, Yao

    2016-03-01

    Enterovirus 71 (EV71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM) single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3) of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2), the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

  9. Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody.

    Directory of Open Access Journals (Sweden)

    Xiaohua Ye

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3 of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2, the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

  10. The changing seroepidemiology of enterovirus 71 infection among children and adolescents in Singapore

    Directory of Open Access Journals (Sweden)

    James Lyn

    2011-10-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 has caused recurrent epidemics of hand, foot and mouth disease among children in Singapore. Between August 2008 and July 2010, we conducted a survey to estimate the seroprevalence of EV71 infection among children and adolescents aged 1-17 years. We compared our EV71 seroepidemiologic findings with a previous study conducted in 1996-1997. Methods The survey involved the prospective collection of 1,200 residual sera from Singapore residents aged 1-17 years in two hospitals. Neutralizing antibodies to EV71 were detected by the microneutralization test. The geometric mean titer (GMT of EV71 antibodies and 95% confidence intervals (CI were calculated and compared by age groups. Statistical significance was taken as P Results The overall EV71 antibody prevalence was 26.9% (95% CI: 24.5-29.5%. It increased significantly from 14.3% in children aged 1-6 years to 27.8% in those aged 7-12 years, and reached 38.8% in adolescents aged 13-17 years. The seroconversion rate differed by about 12% between the consecutive age groups. The GMT of EV71 antibodies was higher among primary school children aged 7-12 years in our study than that among the 6-12 year age group in the 1996-1997 study. Conclusions Higher antibody titers were observed in children aged 1-6 years than those in the other two age groups, indicating that most of the infections had been acquired during early childhood. EV71 infection is common among children and adolescents in Singapore, with 39% infected by the time they are in secondary school (13-17 years of age.

  11. Antigenic and genetic diversity of human enterovirus 71 from 2009 to 2012, Taiwan.

    Directory of Open Access Journals (Sweden)

    Yuan-Pin Huang

    Full Text Available Different subgenogroups of enterovirus 71 (EV-71 have caused numerous outbreaks of hand, foot, and mouth disease worldwide, especially in the Asia-Pacific region. During the development of a vaccine against EV-71, the genetic and antigenic diversities of EV-71 isolates from Taiwan were analyzed by phylogenetic analyses and neutralization tests. The results showed that the dominant genogroups had changed twice, from B to C and from C to B, between 2009 and 2012. The subgenogroup B5 (B5b cluster was dominant in 2008-2009 but was replaced by subgenogroup C4 in 2010-2011. From the end of 2011 to 2012, the re-emerging subgenogroup B5 (B5c cluster was identified as the dominant subgenogroup of EV-71 outbreaks, and subgenogroups C2 and C4 were detected in sporadic cases. Interestingly, the amino acid substitution at position 145 in the VP1 gene was observed in some strains isolated from patients with acute flaccid paralysis. Furthermore, thirty-five strains and their corresponding serum samples were used to analyze the cross-protections and antigenic diversities among different subgenogroups (C4a, C5, B4, B5b, B5c, and C2-like of EV-71. Evident antigenic diversity existed only for the C2-like subgenogroup, which was not effectively neutralized by other serum samples. In contrast, the anti-C2-like serum sample showed broad cross-reactivity against all other subgenogroups. Therefore, these results may provide valuable information for the selection of EV-71 vaccine candidates and the evolution of EV-71 subgenogroups in Taiwan from 2009 to 2012.

  12. Maternal Enterovirus Infection during Pregnancy as a Risk Factor in Offspring Diagnosed with Type 1 Diabetes between 15 and 30 Years of Age

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    Maria Elfving

    2008-01-01

    Full Text Available Maternal enterovirus infections during pregnancy may increase the risk of offspring developing type 1 diabetes during childhood. The aim of this study was to investigate whether gestational enterovirus infections increase the offspring's risk of type 1 diabetes later in life. Serum samples from 30 mothers without diabetes whose offspring developed type 1 diabetes between 15 and 25 years of age were analyzed for enterovirus-specific immunoglobulin M (IgM antibodies and enterovirus genome (RNA, and compared to a control group. Among the index mothers, 9/30 (30% were enterovirus IgM-positive, and none was positive for enterovirus RNA. In the control group, 14/90 (16% were enterovirus IgM-positive, and 4/90 (4% were positive for enterovirus RNA (n.s.. Boys of enterovirus IgM-positive mothers had approximately 5 times greater risk of developing diabetes (OR 4.63; 95% CI 1.22–17.6, as compared to boys of IgM-negative mothers (P<.025. These results suggest that gestational enterovirus infections may be related to the risk of offspring developing type 1 diabetes in adolescence and young adulthood.

  13. Mixed cells in shell vials for detection of influenza viruses and enteroviruses from clinical specimens

    Institute of Scientific and Technical Information of China (English)

    汪千力

    2013-01-01

    Objective To evaluate shell vials of MHV,a combination of Madin-Darby canine kidney cells(MDCK),human epidermoid cancer cells(Hep-2) and African green monkey kidney cells(Vero), and conventional cell culture in detecting influenza viruses and enterovirus from

  14. Enterovirus D68-associated community-acquired pneumonia in children living in Milan, Italy

    NARCIS (Netherlands)

    Esposito, Susanna; Zampiero, Alberto; Ruggiero, Luca; Madini, Barbara; Niesters, Hubert; Principi, Nicola

    2015-01-01

    Background: An increasing number of children infected by enterovirus D68 (EV-D68) and affected by severe respiratory illness, muscle weakness and paralysis were described in the USA and Canada in 2014 Objectives: To investigate the potential involvement of EV-D68 in determining community-acquired pn

  15. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies

    DEFF Research Database (Denmark)

    Nielsen, Trine Skov; Hansen, Jakob; Nielsen, Lars Peter

    2014-01-01

    of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material. METHODS: We collected all autopsy cases diagnosed with myocarditis...

  16. High seroprevalence of enterovirus infections in apes and old world monkeys.

    Science.gov (United States)

    Harvala, Heli; McIntyre, Chloe L; Imai, Natsuko; Clasper, Lucy; Djoko, Cyrille F; LeBreton, Matthew; Vermeulen, Marion; Saville, Andrew; Mutapi, Francisca; Tamoufé, Ubald; Kiyang, John; Biblia, Tafon G; Midzi, Nicholas; Mduluza, Takafira; Pépin, Jacques; Njouom, Richard; Njoum, Richard; Smura, Teemu; Fair, Joseph N; Wolfe, Nathan D; Roivainen, Merja; Simmonds, Peter

    2012-02-01

    To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates.

  17. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Q.; Langereis, M.A.; Lork, M.; Nguyen, M.H.; Hato, S.V.; Lanke, K.H.W.; Emdad, L.; Bhoopathi, P.; Fisher, P.B.; Lloyd, R.E.; Kuppeveld, F.J.M. van

    2014-01-01

    RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress interfer

  18. Evolutionary trajectory of the VP1 gene of human enterovirus 71 genogroup B and C viruses

    NARCIS (Netherlands)

    S.M.G. van der Sanden (Sabine); H.G.A.M. van der Avoort (Harrie); P. Lemey (Philippe); G. Uslu (Gökhan); M.P.G. Koopmans D.V.M. (Marion)

    2010-01-01

    textabstractFrom 1963 to 1986, human enterovirus 71 (HEV71) infections in the Netherlands were successively caused by viruses of subgenogroups B0, B1 and B2. A genogroup shift occurred in 1987, after which viruses of subgenogroups C1 and C2 were detected exclusively. This is in line with HEV71 typin

  19. Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010.

    NARCIS (Netherlands)

    Meijer, A.; Sanden, S. van der; Snijders, B.E.P.; Jaramillo-Gutierrez, G.; Bont, L.; Ent, C.K. van der; Overduin, P.; Jenny, S.L.; Jusic, E.; Avoort, H.G.A.M. van der; Smith, G.J.D.; Donker, G.A.; Koopmans, M.P.G.

    2012-01-01

    Following an increase in detection of enterovirus 68 (EV68) in community surveillance of respiratory infections in The Netherlands in 2010, epidemiological and virological analyses were performed to investigate the possible public health impact of EV68 infections. We retrospectively tested specimens

  20. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A; Lork, Marie; Nguyen, Mai; Hato, Stanleyson V; Lanke, Kjerstin; Emdad, Luni; Bhoopathi, Praveen; Fisher, Paul B; Lloyd, Richard E; van Kuppeveld, Frank J M

    2014-01-01

    UNLABELLED: RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppr

  1. Enterovirus D68-associated community-acquired pneumonia in children living in Milan, Italy

    NARCIS (Netherlands)

    Esposito, Susanna; Zampiero, Alberto; Ruggiero, Luca; Madini, Barbara; Niesters, Hubert; Principi, Nicola

    2015-01-01

    Background: An increasing number of children infected by enterovirus D68 (EV-D68) and affected by severe respiratory illness, muscle weakness and paralysis were described in the USA and Canada in 2014 Objectives: To investigate the potential involvement of EV-D68 in determining community-acquired pn

  2. Biological characteristics and research progress of enterovirus 71%肠道病毒71型的生物学特征及研究进展

    Institute of Scientific and Technical Information of China (English)

    戈小琴; 李鸿钧

    2010-01-01

    In recent years, the prevalence of enterovirus 71 (EV71) shows rising trend in Asia-Pacific area. The hand, foot and mouth disease caused by EV71 attracts widespread attention, and becomes a large challenge for preventive medicine and basic scientific research. This paper reviews research progress in biological characteristics, epidemiology, pathogenesis, clinical and laboratory diagnosis, prevention, and treatment of EV71.%近年来,肠道病毒71型(enterovirus 71,EV71)的流行在亚太地区呈逐渐上升趋势.EV71导致的手足口病已引起社会各界广泛关注,并成为医学预防和基础科研的挑战.此文就EV71的生物学特性、流行病学、致病机制、临床和实验室诊断、预防及治疗等方面的研究进展作一综述.

  3. The evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water matrices

    Data.gov (United States)

    U.S. Environmental Protection Agency — The data to support the evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water...

  4. Norepinephrine and Epinephrine Enhanced the Infectivity of Enterovirus 71.

    Directory of Open Access Journals (Sweden)

    Yu-Ting Liao

    Full Text Available 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.The aims of this study were to explore the effects of catecholamines on severe EV71 infection and to investigate the changes in the percentages of EV71-infected cells, virus titer, and cytokine production on the involvement of catecholamines.Plasma levels of norepinephrine (NE and epinephrine (EP in EV71-infected patients were measured using an enzyme-linked immunoassay. The expression of adrenergic receptors (ADRs on RD, A549, SK-N-SH, THP-1, Jurkat and human peripheral blood mononuclear cells (hPBMCs were detected using flow cytometry. The percentages of EV71-infected cells, virus titer, and cytokine production were investigated after treatment with NE and EP.The plasma levels of NE and EP were significantly higher in EV71-infected patients with ANS dysregulation and PE than in controls. Both α1A- and β2-ADRs were expressed on A549, RD, SK-N-SH, HL-60, THP-1, Jurkat cells and hPBMCs. NE treatment elevated the percentages of EV71-infected cells to 62.9% and 22.7% in THP-1 and Jurkat cells, respectively. Via treatment with EP, the percentages of EV71-infected cells were increased to 64.6% and 26.9% in THP-1 and Jurkat cells. The percentage of EV71-infected cells increased upon NE or EP treatment while the α- and β-blockers reduced the percentages of EV71-infected cells with NE or EP treatment. At least two-fold increase in virus titer was observed in EV71-infected A549, SK-N-SH and hPBMCs after treatment with NE or EP. IL-6 production was enhanced in EV71-infected hPBMCs at a concentration of 102 pg/mL NE.The plasma levels of NE and EP elevated in EV71-infected patients with ANS

  5. Viral kinetics of Enterovirus 71 in human habdomyosarcoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Lu; Ya-Qing He; Li-Na Yi; Hong Zan; Hsiang-Fu Kung; Ming-Liang He

    2011-01-01

    AIM: To characterise the viral kinetics of enterovirus 71 (EV71). METHODS: In this study, human rhabdomyosarcoma (RD) cells were infected with EV71 at different multiplicity of infection (MOI). After infection, the cytopathic effect (CPE) was monitored and recorded using a phase contrast microscope associated with a CCD camera at different time points post viral infection (0, 6, 12, 24 h post infection). Cell growth and viability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both EV71 infected and mock infected cells at each time point. EV71 replication kinetics in RD cells was determined by measuring the total intracellular viral RNA with real-time reverse-transcription polymerase chain reaction (qRT-PCR). Also, the intracellular and extracellular virion RNA was isolated and quantified at different time points to analyze the viral package and secretion. The expression of viral protein was determined by analyze the levels of viral structure protein VP1 with Western blotting. RESULTS: EV71 infection induced a significant CPE as early as 6 h post infection (p.i.) in both RD cells infected with high ratio of virus (MOI 10) and low ratio of virus (MOI 1). In EV71 infected cells, the cell growth was inhibited and the number of viable cells was rapidly decreased in the later phase of infection. EV71 virions were uncoated immediately after entry. The intracellular viral RNA began to increase at as early as 3 h p.i. and the exponential increase was found between 3 h to 6 h p.i. in both infected groups. For viral structure protein synthesis, results from western-blot showed that intracellular viral protein VP1 could not be detected until 6 h p.i. in the cells infected at either MOI 1 or MOI 10; and reached the peak at 9 h p.i. in the cells infected with EV71 at both MOI 1 and MOI 10. Simultaneously, the viral package and secretion were also actively processed as the virus underwent rapid replication. The viral package kinetics

  6. Evolutionary pattern of 5’-UTR of enteroviruses and primer update for the detection of enteroviral RNA in environmental samples

    Institute of Scientific and Technical Information of China (English)

    Nabil Ben Salem Abid; Zyed Rouis; Mahjoub Aouni

    2012-01-01

    Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods:Nucleotide sequence analysis of enteroviruses deposited in the international databaseGenBank (www.ncbi.nlm.nih.gov/Genbank) was conducted to develop specific primers for the detection of these viruses.The specificity and sensitivity of the method were tested using coxackievirus B3 strainNancy, environmental isolate of human hepatitisA virus and human rotavirus strain WA.Seventy sewage samples were analyzed.Results:Enterovirus genome was detected in all positive samples.The genome of enterovirus was not detected in negative samples.The level of detection of these viruses was102TCID50/mL.Conclusions:The development of new primers is an important issue for the detection of enteroviruses in the environment and the assessment of risk factors to human health.

  7. Association of Tic Disorders and Enterovirus Infection: A Nationwide Population-Based Study.

    Science.gov (United States)

    Tsai, Ching-Shu; Yang, Yao-Hsu; Huang, Kuo-You; Lee, Yena; McIntyre, Roger S; Chen, Vincent Chin-Hung

    2016-04-01

    There has been growing interest in the association between infectious disease and mental disorders, but an association between enterovirus (EV) infection and tic disorders has not been sufficiently explored. Herein, we aim to investigate the association between EV infection and incidence of tic disorders in a nationwide population-based sample using Taiwan's National Health Insurance Research Database. We identified individuals aged ≤18 years prior to 2005 with an inpatient diagnosis of EV infection and/or history of EV infection. Tic disorder was operationalized using International Classification of Disease, Revision 9, Clinical Modification (ICD-9-CM) codes 307.20-307.23. A total of 47,998 individuals with history of EV infection were compared to 47,998 sex-, age-, and urbanization-matched controls on incidence of tic disorders. The mean ± standard deviation follow-up period for all subjects was 9.7 ± 3.6 years; the mean latency period between initial EV infection and incident diagnosis of tic disorder diagnosis was 5.4 ± 2.8 years. EV infection was significantly associated with greater incidence of tic disorders (hazard ratio [HR] = 1.24, 95% CI: 1.07-1.45). When subgrouped on the basis of central nervous system (CNS) involvement, EV infection with CNS involvement was not significantly associated with greater incidence of tic disorders when compared to controls (HR = 1.25, 95% CI: 0.64-2.43); EV infection without CNS involvement was significantly associated greater incidence of tic disorders when compared to controls (HR = 1.24, 95% CI: 1.07-1.45). In addition, hospitalization for an EV infection did not increase the hazard for greater incidence of tic disorders (HR = 1.32, 95% CI: 1.04-1.67 with hospitalization and 1.22, 95% CI: 1.04-1.44 without hospitalization). EV infection is temporally associated with incidence of tic disorders. Our observations add to the growing body of literature implicating immune-inflammatory system in

  8. 肠道病毒71型基因重组的研究进展%Progress in research on gene recombination of enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    姚昕

    2013-01-01

    肠道病毒71型(Enterovirus 71,EV71)是手足口病(Hand,foot and mouth disease,HFMD)的主要病原体,属于肠道小RNA病毒,这类病毒的基因组由脆性平链RNA组成,易断裂,有较高的突变性.在混合感染中会发生同型不同株不同亚型,或同属不同型间的基因交换形成新的重组病毒,EV71也具有重组特性.新形成的重组病毒可能导致其生物学特性和致病性的改变,进而影响疾病的防控.本文就EV71病毒基因重组及可能引发的防控问题进行综述.%As the major pathogen of hand, foot and mouth disease (HFMD), enterovirus 71 (EV71) belongs to enteric small RNA virus. The genomes of this kind of viruses consist of friable flat chain RNAs which show high mutagenicity and are easy to be broken. In mixed infection, novel recombinant viruses may formed by gene exchange between different strains or subtypes of the same type, or between the different types of the same genus, which may result in the change of biological characters and pathogenesis of the viruses, thus influence the prevention and control of relevant diseases. The paper attempts to give a review on EV71 gene recombination as well as the resulted problems in prevention and control of the virus.

  9. 肠道病毒71型灭活疫苗相关研究现状%Current status of research of inactivated enterovirus 71 vaccines

    Institute of Scientific and Technical Information of China (English)

    杨二霞

    2013-01-01

    Hand-foot-and-mouth disease (HFMD) is a life-threatening infectious disease of children under 5 years old.In recent years,major outbreaks of HFMD caused by enterovirus 71 (EV71) have emerged in the Asia-Pacific region,and have resulted in millions of cases and hundreds of deaths each year in China since 2008.Because EV71 is one of the main pathogens of HFMD resulting in severe diseases and death,the pathogenesis of HFMD is still unclear,and no effective therapeutic drugs for EV71 infection are currently available,development of vaccines against EV71 is urgently needed.This review summarizes research progress of inactivated EV71 vaccines.%手足口病是一种威胁5岁以下儿童生命健康的传染病,近年来已在亚太地区造成了多次上百万患者发病的大规模暴发,仅在中国大陆,自2008年以来,每年发病人数就超过百万,死亡数百人.然而,由于肠道病毒71型(enterovirus 71,EV71)是导致重症和死亡病例的主要病原体,而其致病机制尚不清楚,目前尚无有效的治疗性药物,因此EV71疫苗研究成为迫切需要解决的问题.此文就EV71灭活疫苗研究进展进行综述.

  10. Positive Selection Analysis of VP1 Genes of Worldwide Human Enterovirus 71 Viruses

    Institute of Scientific and Technical Information of China (English)

    Wei-feng SHI; Zhong ZHANG; Ai-she DUN; Yan-zhou ZHANG; Guang-fu YU; Dong-ming ZHUANG; Chao-dong ZHU

    2009-01-01

    Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.

  11. Genome Sequence of Enterovirus D68 from St. Louis, Missouri, USA, 2016

    Science.gov (United States)

    Wylie, Todd N.; Storch, Gregory A.

    2017-01-01

    ABSTRACT Enterovirus D68 (EV-D68) was rarely observed prior to a widespread outbreak in 2014. We observed its reemergence in St. Louis in 2016 and sequenced the EV-D68 genomes from two patient samples. The 2016 viruses in St. Louis differed from those we had sequenced from the 2014 outbreak but were similar to other viruses circulating nationally in 2016. PMID:28254971

  12. [Experience in the use of chemical compounds for the primary identification and differentiation of enteroviruses].

    Science.gov (United States)

    Amvros'eva, T V; Votiakov, V I; Andreeva, O T; Kazinets, O N; Bogush, Z F; Sharko, R M; Kvacheva, Z B

    2003-02-01

    Data on the usage of chemical inhibitors nifan and belvtazid, which possess a selective and antienteroviral effect, in the primary identification of enteroviruses and their differentiation into polio- and non-poliomyelytic ones isolated from human clinical materials or the environment by using the cell culture are presented in the article. The method is recommended for the practical use by the virology service in the diagnostics of enteroviral infections and in the identification of cytopathic agents isolated from the enviroment.

  13. Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.

    Directory of Open Access Journals (Sweden)

    Hendrik Jan Thibaut

    2014-04-01

    Full Text Available Enteroviruses (family of the Picornaviridae cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH, thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis.

  14. Epidemiology of Enterovirus 71 in The Netherlands, 1963 to 2008▿

    OpenAIRE

    Sanden, Sabine; Koopmans, Marion; Uslu, Gökhan; Avoort, Harrie

    2009-01-01

    The incidence of enterovirus 71 (EV71) infection has greatly increased in the Asian Pacific region since 1997. Several large outbreaks, caused by different subgenogroups of EV71, occurred with high rates of morbidity and a substantial number of deaths. In 2007, 58 cases of EV71 infection requiring hospitalization were reported in The Netherlands after a period of low endemicity of 21 years. These events triggered a study on the epidemiology of EV71 in The Netherlands. Genetic analysis of the ...

  15. Frequency of enterovirus detection in blood samples of neonates admitted to hospital with sepsis-like illness in Kuwait.

    Science.gov (United States)

    Ahmad, Suhail; Dalwai, Ajmal; Al-Nakib, Widad

    2013-07-01

    This study investigated the role of enteroviruses in sepsis-like illness among neonates in Kuwait. Serum samples from 139 consecutive neonates presenting with sepsis-like illness during a three and a half-year-period whose blood cultures were negative for bacterial pathogens were tested. Enterovirus RNA was detected by single-step reverse-transcription PCR (RT-PCR). Specific genotypes were identified by direct DNA sequencing of enteroviral genome. Serotype-specific antibodies in serum samples from some selected patients were detected by virus neutralization test using coxsackievirus B types (CBVs). All 139 neonates presented with sepsis-like illness and blood samples were uniformly negative for aerobic/anaerobic bacterial cultures. Fifty-six (40%) neonates had further complications of sepsis including carditis (n = 34) and multi-organ involvement (n = 22). Enterovirus RNA was detected by RT-PCR in 34 of 139 (24%) serum samples which is among the highest frequency reported so far in non-epidemic settings. Genotyping identified CBVs as most common enteroviruses, causing 19 of 34 (56%) enteroviral sepsis episodes in neonates. Of 34 carditis cases, 18 were positive for CBVs by serotyping including all 10 enterovirus RNA-positive samples. Only one fatality was observed due to liver failure in a neonate with hepatitis. Our data showed that enteroviruses are responsible for 24% of neonatal sepsis cases due to non-bacterial causes in Kuwait. The data indicate that enteroviruses should be considered in the differential diagnosis of sepsis-like illness among neonates, particularly those with negative blood cultures for bacterial pathogens. Copyright © 2013 Wiley Periodicals, Inc.

  16. Case of a healthy infant born following antenatal enterovirus myocarditis and hydrops.

    Science.gov (United States)

    Bonnin, Aurore; Tassin, Mikael; Vauloup-Fellous, Christelle; Letamendia, Emmanuelle; Stos, Bertrand; Bonnet, Damien; Gajdos, Vincent; Mabille, Mylène; Benachi, Alexandra

    2014-11-01

    Fetal hydrops and myocarditis were diagnosed in a woman at 32 weeks of gestation (WG). Transplacental enterovirus infection was suspected because all other causes of myocarditis and hydrops were excluded, it was during an endemic period, and there was a setting of maternal infection (fever a few days before). We opted for in utero treatment because of the risk of resuscitating a neonate with myocarditis and hydrops. We administered dexamethasone 12mg twice for pulmonary maturation and presumed it would partially improve the myocarditis. Fetal arrhythmia was noted at 35 WG and we decided to deliver the infant as postnatal treatment of the heart disorder would be more effective. RT-PCR (ARGENE(®)) showed that the neonate's throat and anal tissues and cord blood sampled on the day of birth contained enterovirus ribonucleic acid and coxsackievirus B5, as did the mother's anal sample. Laboratory tests, heart MRI and probably brain MRI indicated neonatal enterovirus infection. Findings were normal at two-year follow-up.

  17. Analysis of enterovirus and adenovirus presence in swimming pools in Cyprus from 2007-2008.

    Science.gov (United States)

    Bashiardes, S; Koptides, D; Pavlidou, S; Richter, J; Stavrou, N; Kourtis, C; Papageorgiou, G T; Christodoulou, C G

    2011-01-01

    An analysis was carried out to determine the presence of enteroviruses and adenoviruses in public swimming pools in Cyprus. The effectiveness of the commonly implemented disinfection procedure of chlorination was confirmed by determination of bacteriological markers. Analysis of viral presence was carried out by sampling random swimming pools from the five major cities in Cyprus during a period of 21 months spanning from April 2007 to December 2008. A 10 I sample was taken from each swimming pool to be tested and was subsequently concentrated via membrane filtration using a new methodological approach for virus elution. Concentrated samples were analysed using of a Real Time Polymerase Chain Reaction (PCR) TaqMan probe based approach to detect the presence of enteroviruses and adenoviruses. Over the period of 21 months a total of 126 swimming pools were sampled and analysed. In four swimming pools enteroviruses were detected, in one pool echovirus 18 was identified, in two pools echovirus 30 was identified and in one other pool poliovirus Sabin 1 was identified. Similarly, in four swimming pools adenoviruses were detected, in all four adenovirus 41 was identified. Bacteriological marker analysis showed that 98% of pools complied with Cyprus regulations.

  18. Itraconazole Inhibits Enterovirus Replication by Targeting the Oxysterol-Binding Protein

    Directory of Open Access Journals (Sweden)

    Jeroen R.P.M. Strating

    2015-02-01

    Full Text Available Itraconazole (ITZ is a well-known antifungal agent that also has anticancer activity. In this study, we identify ITZ as a broad-spectrum inhibitor of enteroviruses (e.g., poliovirus, coxsackievirus, enterovirus-71, rhinovirus. We demonstrate that ITZ inhibits viral RNA replication by targeting oxysterol-binding protein (OSBP and OSBP-related protein 4 (ORP4. Consistently, OSW-1, a specific OSBP/ORP4 antagonist, also inhibits enterovirus replication. Knockdown of OSBP inhibits virus replication, whereas overexpression of OSBP or ORP4 counteracts the antiviral effects of ITZ and OSW-1. ITZ binds OSBP and inhibits its function, i.e., shuttling of cholesterol and phosphatidylinositol-4-phosphate between membranes, thereby likely perturbing the virus-induced membrane alterations essential for viral replication organelle formation. ITZ also inhibits hepatitis C virus replication, which also relies on OSBP. Together, these data implicate OSBP/ORP4 as molecular targets of ITZ and point to an essential role of OSBP/ORP4-mediated lipid exchange in virus replication that can be targeted by antiviral drugs.

  19. Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children

    Science.gov (United States)

    Cuevas, María Teresa; Pozo, Francisco; García-García, María Luz; Molinero, Mar; Calderón, Ana; Gonzalez-Esguevillas, Mónica; Pérez-Sautu, Unai; Casas, Inmaculada

    2016-01-01

    Background: The incidence of enterovirus D68 (EV-D68) and the spectrum of clinical disease in children are not well known in European countries. We have designed a study with the objective of describing the clinical impact of EV-D68 detected in children with respiratory tract infections. Methods: As a part of a prospective study to identify the etiology and clinical characteristics of viral respiratory infections in children in Spain, we performed the analysis of the cases of EV infections in all children hospitalized in a secondary hospital in Madrid, during the epidemic respiratory season 2012–2013. A second group of samples was corresponded to infants of the same area, with ambulatory respiratory infection or asymptomatic. Phylogenetic EV-D68 analysis was made using the viral protein 1 gene (VP1). Clinical data of EV-D68 patients were compared with those infected by rhinovirus in the same period and population. Results: The study population consisted of 720 patients corresponding to 399 episodes of hospitalization for respiratory causes, 44 episodes of ambulatory respiratory infections and 277 children determined as a healthy control group. A total of 22 patients were positive for EVs (3.05%), and 12 of them were specifically typed as EV-D68 (11/443 respiratory infections, 2.5%). The most frequent diagnosis in the 10 hospitalized children with EV-D68 detection was recurrent wheezing. Hypoxia was present in 70% of cases, but admission in the intensive care unit was not required. No neurological signs or symptoms were observed. One patient had an ambulatory mild bronchiolitis and another was asymptomatic. No differences were found with rhinovirus infections except less duration of hypoxia and fever in EV-D68 group. Conclusions: EV-D68 infections were detected in 3.05% of respiratory studied samples (2.5% of admissions). The infection was associated with wheezing episodes with hypoxia. No admissions to intensive care unit or neurological symptoms were found. PMID

  20. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    Directory of Open Access Journals (Sweden)

    Ai-Hsiang Chou

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 has caused several epidemics of hand, foot and mouth diseases (HFMD in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration, a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice

  1. Pyrrolidine dithiocarbamate inhibits enterovirus 71 replication by down-regulating ubiquitin-proteasome system.

    Science.gov (United States)

    Lin, Lexun; Qin, Ying; Wu, Heng; Chen, Yang; Wu, Shuo; Si, Xiaoning; Wang, Hui; Wang, Tianying; Zhong, Xiaoyan; Zhai, Xia; Tong, Lei; Pan, Bo; Zhang, Fengmin; Zhong, Zhaohua; Wang, Yan; Zhao, Wenran

    2015-01-02

    Enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD). The severe neurological complications caused by EV71 infection and the lack of effective therapeutic medicine underline the importance of searching for antiviral substances. Pyrrolidine dithiocarbamate (PDTC), an antioxidant, has been reported to inhibit the replication of coxsackievirus B (CVB) through dysregulating ubiquitin-proteasome system (UPS). In this study, we demonstrated that PDTC exerted potent antiviral effect on EV71. Viral RNA synthesis, viral protein expression, and the production of viral progeny were significantly reduced by the treatment of PDTC in Vero cells infected with EV71. Similar to the previous report about the inhibitory effect of PDTC on UPS, we found that PDTC treatment led to decreased levels of polyubiquitinated proteins in EV71-infected cells. The inhibitory effect of PDTC on UPS was further confirmed by the increased accumulation of cell cycle regulatory proteins p21 and p53, which are normally degraded through UPS, while the expression levels of both proteins remained unchanged. We also showed that PDTC had no impact on the activity of proteasome. Thus, we demonstrated that the down-regulation of PDTC on UPS was the result of its inhibition on ubiquitination. More importantly, this study provides evidence that the inhibition on UPS was required for the antiviral activity of PDTC, since MG132, a potent proteasome inhibitor, significantly inhibited the cytopathic effect and viral protein synthesis in EV71-infected cells. We also found that the antioxidant property of PDTC did not contribute to its antiviral effect, since N-acetyl-l-cysteine, a potent antioxidant, could not inhibit viral replication. In addition, CPE and viral protein synthesis were not inhibited in the cells pretreated with PDTC 2h before viral infection and then cultured in the media with no PDTC supplement, while the antioxidant effect of PDTC was retained. PDTC also

  2. Molecular epidemiology of enterovirus 71 infection in the central region of Taiwan from 2002 to 2012.

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wu

    Full Text Available Enterovirus 71 (EV71, a causative agent of hand, foot, and mouth disease can be classified into three genotypes and many subtypes. The objectives of this study were to conduct a molecular epidemiological study of EV71 in the central region of Taiwan from 2002-2012 and to test the hypothesis that whether the alternative appearance of different EV71 subtypes in Taiwan is due to transmission from neighboring countries or from re-emergence of pre-existing local strains. We selected 174 EV71 isolates and used reverse transcription-polymerase chain reaction to amplify their VP1 region for DNA sequencing. Phylogenetic analyses were conducted using Neighbor-Joining, Maximum Likelihood and Bayesian methods. We found that the major subtypes of EV71 in Taiwan were B4 for 2002 epidemic, C4 for 2004-2005 epidemic, B5 for 2008-2009 epidemic, C4 for 2010 epidemic and B5 for 2011-2012 epidemic. Phylogenetic analysis demonstrated that the 2002 and 2008 epidemics were associated with EV71 from Malaysia and Singapore; while both 2010 and 2011-2012 epidemics originated from different regions of mainland China including Shanghai, Henan, Xiamen and Gong-Dong. Furthermore, minor strains have been identified in each epidemic and some of them were correlated with the subsequent outbreaks. Therefore, the EV71 infection in Taiwan may originate from pre-existing minor strains or from other regions in Asia including mainland China. In addition, 101 EV71 isolates were selected for the detection of new recombinant strains using the nucleotide sequences spanning the VP1-2A-2B region. No new recombinant strain was found. Analysis of clinical manifestations showed that patients infected with C4 had significantly higher rates of pharyngeal vesicles or ulcers than patients infected with B5. This is the first study demonstrating that different EV 71 genotypes may have different clinical manifestations and the association of EV71 infections between Taiwan and mainland China.

  3. Antiviral effects of two Ganoderma lucidum triterpenoids against enterovirus 71 infection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenjing; Tao, Junyan; Yang, Xiaoping [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Yang, Zhuliang [Key Laboratory of Biodiversity and Biogeography, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201 (China); Zhang, Li; Liu, Hongsheng [Department of Academy of Sciences, Liaoning University, Shenyang 110036 (China); Wu, Kailang [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China); Wu, Jianguo, E-mail: jwu@whu.edu.cn [State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan 430072 (China)

    2014-07-04

    Highlights: • Triterpenoids GLTA and GLTB display anti-EV71 activities without cytotoxicity. • The compounds prevent EV71 infection by blocking adsorption of the virus to the cells. • GLTA and GLTB bind to EV71 capsid at the hydrophobic pocket to block EV71 uncoating. • The two compounds significantly inhibit the replication of EV71 viral RNA. • GLTA and GLTB may be used as potential therapeutic agents to treat EV71 infection. - Abstract: Enterovirus 71 (EV71) is a major causative agent for hand, foot and mouth disease (HFMD), and fatal neurological and systemic complications in children. However, there is currently no clinical approved antiviral drug available for the prevention and treatment of the viral infection. Here, we evaluated the antiviral activities of two Ganoderma lucidum triterpenoids (GLTs), Lanosta-7,9(11),24-trien-3-one,15;26-dihydroxy (GLTA) and Ganoderic acid Y (GLTB), against EV71 infection. The results showed that the two natural compounds display significant anti-EV71 activities without cytotoxicity in human rhabdomyosarcoma (RD) cells as evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The mechanisms by which the two compounds affect EV71 infection were further elucidated by three action modes using Ribavirin, a common antiviral drug, as a positive control. The results suggested that GLTA and GLTB prevent EV71 infection through interacting with the viral particle to block the adsorption of virus to the cells. In addition, the interactions between EV71 virion and the compounds were predicated by computer molecular docking, which illustrated that GLTA and GLTB may bind to the viral capsid protein at a hydrophobic pocket (F site), and thus may block uncoating of EV71. Moreover, we demonstrated that GLTA and GLTB significantly inhibit the replication of the viral RNA (vRNA) of EV71 replication through blocking EV71 uncoating. Thus, GLTA and GLTB may represent two potential

  4. Pilot scale production of highly efficacious and stable enterovirus 71 vaccine candidates.

    Science.gov (United States)

    Chou, Ai-Hsiang; Liu, Chia-Chyi; Chang, Cheng-Peng; Guo, Meng-Shin; Hsieh, Shih-Yang; Yang, Wen-Hsueh; Chao, Hsin-Ju; Wu, Chien-Long; Huang, Ju-Lan; Lee, Min-Shi; Hu, Alan Yung-Chi; Lin, Sue-Chen; Huang, Yu-Yun; Hu, Mei-Hua; Chow, Yen-Hung; Chiang, Jen-Ron; Chang, Jui-Yuan; Chong, Pele

    2012-01-01

    Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. These

  5. Hexon-modified recombinant E1-deleted adenoviral vectors as bivalent vaccine carriers for Coxsackievirus A16 and Enterovirus 71.

    Science.gov (United States)

    Zhang, Chao; Yang, Yong; Chi, Yudan; Yin, Jieyun; Yan, Lijun; Ku, Zhiqiang; Liu, Qingwei; Huang, Zhong; Zhou, Dongming

    2015-09-22

    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 Coxsackievirus A16 (CA16), PEP71, into hypervariable region 1 (HVR1), and a shortened neutralising epitope of Enterovirus 71 (EV71), sSP70, into HVR2 of the AdC68 hexon. In order to enhance the immunogenicity of EV71, VP1 of EV71 was cloned into the E1-region of the AdC68 vectors. The results demonstrated that these two epitopes were well presented on the virion surface and had high affinity towards specific antibodies, and VP1 of EV71 was also significantly expressed. In pre-clinical mouse models, the hexon-modified AdC68 elicited neutralising antibodies against both CA16 and EV71, which conferred protection to suckling mice against a lethal challenge of CA16 and EV71. In summary, this study demonstrates that the hexon-modified AdC68 may represent a promising bivalent vaccine carrier against EV71 and CA16 and an epitope-display platform for other pathogens.

  6. Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice

    Directory of Open Access Journals (Sweden)

    Huang Szu-Wei

    2011-11-01

    Full Text Available Abstract Background Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71 strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE, was not evident. Methods To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection. Results After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-γ, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-γ provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71-infected, but not herpes simplex virus-1 (HSV-1-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS. While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only. Conclusions Exogenous IL-6, IL-13, and IFN-γ treatment could induce mild PE and exacerbate pulmonary abnormality of EV71-infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms.

  7. RNA polymerase I-driven reverse genetics system for enterovirus 71 and its implications for vaccine production

    Directory of Open Access Journals (Sweden)

    Meng Tao

    2012-10-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 is a virus that causes from mild hand, foot and mouth disease (HFMD to severe neurological complications and deaths in infants and young children. Effective antiviral agents and vaccines against EV71 are not available. However, Vero cell-based chemically inactivated EV71 vaccines could be developed soon based on the success of inactivated polio vaccine. Like poliovirus, EV71 has a positive single-stranded RNA genome of about 7400 nucleotides which contains a single open reading frame (ORF flanked by conserved and untranslated regions at both the 5′ and 3′ ends. Results The universal amplification of the full length genome of EV71 regardless of its genetic diversity, and the subsequent construction of a human RNA polymerase I-driven reverse genetics (RG system to produce pure virus stocks in Vero cell within 10 days were described. The rescued viruses were characterized by DNA sequencing, cytopathic effect (CPE and indirect fluorescent assay (IFA in comparison with the wild-type viruses. Moreover, the rescued viruses grew to high titers and retained the same immunogenicity as the wild-type viruses. Conclusion We have established a simplified method to rescue RG EV71 virus from diverse clinical isolates with detailed genetic information and to prepare virus stocks in only 10 days. This method could accelerate EV71 vaccine development.

  8. The developments in the diagnosis of the enteroviruses 71%肠道病毒71型实验室诊断研究进展

    Institute of Scientific and Technical Information of China (English)

    吴星

    2012-01-01

    肠道病毒71型(Enterovirus 71,EV71)为手足口病(Hand,foot and mouth disease,HFMD)和相关疾病的主要病原体,多感染婴幼儿,少数病例可以并发呼吸道感染和心肌炎、无菌性脑膜炎、脑炎、急性弛缓性麻痹等严重疾病,可致残、致死.因此EV71实验室诊断对EV71引起疾病的治疗和防控具有重要意义.本文将从核酸检测、抗体检测及其他检测等三部分对EV71的实验室诊断方法研究进展进行了综述.

  9. The overview of detection methods of Enterovirus 71%肠道病毒71型检测方法研究概况

    Institute of Scientific and Technical Information of China (English)

    吴海波; 郭潮潭

    2008-01-01

    Enterovirus 71(EV71)is an important pathogen of hand-foot-mouth disease(HFMD),several large outbreaks of EV71 infection have caused serious clinical symptoms and sequels,resulted in dozens of deaths.so more and more people pay attention to EV71.The paper reviews about the basic character and detection methods of EV71.%肠道病毒71型(EV71)是引起手足口病(HFMD)的重要病原,已在世界范围内引起了多次大流行,并导致了严重的并发症和后遗症,甚至死亡,引起了人们越来越多的关注.此文就EV71的基本特征和检测方法研究概况作了介绍.

  10. 肠道病毒71型疫苗的研究进展%Research progress of enterovirus 71 vaccine

    Institute of Scientific and Technical Information of China (English)

    李欢

    2012-01-01

    近年来,手足口病(Hand foot mouth disease,HFMD)在中国多次爆发流行,严重威胁公众健康,尤其是5岁以下的婴幼儿.而肠道病毒71型(Enterovirus 71,EV71)是引起手足口病的主要病原体之一,由于目前还无针对该疾病有效的抗病毒药物,研制疫苗是控制EV71流行最为有效的措施.目前EV71疫苗及相关研究均取得重大突破,本文就近年来关于EV71疫苗研发、动物模型等的研究进展作一综述.

  11. Research on vaccine candidate strains and standards of enterovirus 71 vaccines%肠道病毒71型疫苗候选株和疫苗标准的研究

    Institute of Scientific and Technical Information of China (English)

    梁争论

    2011-01-01

    肠道病毒71型( enterovirus 71,EV71)属小RNA病毒科肠道病毒属,主要引起手足口病(hand-foot-and-mouth disease,HFMD)和中枢神经系统疾病.1969年在美国加里福尼亚分离出首株EV71[1].近年来EV71在亚太地区持续流行[2-9],特别是1998年在中国台湾地区大流行后,开始引起人们的重视.

  12. 肠道病毒71型疫苗研究进展%Research Progress of the Enterovirus Type 71 Vaccine

    Institute of Scientific and Technical Information of China (English)

    李燕; 刘燕敏; 梁晓峰

    2011-01-01

    近几年来,手足口病(Hand,Foot and Mouth Disease,HFMD)受到越来越多的关注.肠道病毒71型(Enterovirus Type 71,EV71)是引起HFMD的病原体之一.由于HFMD重症或死亡病例以EV71为主要病原,且该病尚无特效的治疗药物,因此EV71疫苗成为预防HFMD有效的措施.国内外已有灭活疫苗、减毒活疫苗、亚单位疫苗、病毒样颗粒和脱氧核糖核酸疫苗等多种尝试,但这些疫苗仅在动物模型中进行了评价,尚未实施临床试验.现将EV71疫苗研究进展进行综述.%Recent years, hand, foot and mouth disease(HFMD)caused more and more attention. Enterovirus type 71 (EV71)is one of pathogen caused HFMD. EV7I vaccine is an effective measure to prevent HFMD because of most severe cases and deaths caused by EV7, and there is no effective drugs so far. There are several vaccine candidates! Including inactivated whole virus vaccine?live-attenuated virus vaccine, subunit vaccine, virus-like particle and deoxyribonucleic acid vaccines, which have been trial and evaluated in animals. Clinical trial, however, has not been conducted. The research progress of EV71 vaccine was reviewed in this paper.

  13. 肠道病毒71型感染机制研究进展%Advances in enterovirus A71 infection mechanism

    Institute of Scientific and Technical Information of China (English)

    严文莉(综述); 朱俊萍; 安静(审校)

    2016-01-01

    Enterovirus A71(EV-A71) is the main causative agent of hand-foot and mouth disease (HFMD) , and is in-volved in serious complications and fatal cases attributed to the disease. Numerous outbreaks of HFMD occurred in the A-sia-Pacific region in recent years. As a parasitic microbe, the virus highly depends on the energy and metabolic system of the host cells to establish an effective infection. Recently there are accumulated reports regarding mechanisms of the EV-A71 internalization and uncoating in different host cells, so search for advances on this aspect is benificial to its undestang-ding and providing a scientific basis in prevetion and tretment of HFMD. This review will focus on the advances of research in the early stage of EV-A71 infection.%重症手足口病及其死亡病例多由肠道病毒71型(Enterovirus A71,EV-A71)感染引起,且近年来在亚太地区广泛流行。由于EV-A71具有严格的宿主细胞寄生性,需依赖细胞的能量和代谢系统完成其复制过程。因此研究该病毒在进入、脱衣壳等感染早期过程中病毒与宿主相互作用的机制,不仅有助于理解其致病机理,同时可为建立相应预防和治疗的策略提供科学依据。为此,就EV-A71感染早期的致病机制的研究进展进行了综述。

  14. Progress in research on inactivated whole virus vaccine against enterovirus 71%EV71全病毒灭活疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    姚昕; 毛群颖

    2012-01-01

    Hand, foot and mouth disease(HFMD) has been circulated in China and has become a serious public health problem. Enterovirus 71 (EV71) is emerged as a significant pathogen causing severe and death cases. Various EV71 vaccines are in development for controlling EV71 infection, of which inactivated vaccines are developed rapidly. At present, phase HI clinical trials will be performed on the inactivated whole virus vaccines against EV71 manufactured by three manufacturers in China. This review attempts to give an overview of the progress and quality control of inactivated whole virus vaccine against EV71.%近年来手足口病(Hand,foot and mouth disease,HFMD)在我国持续流行,已经成为危害儿童健康的严重疾病.肠道病毒71型(Enterovirus 71,EV71)感染是引起HFMD病例和婴儿重症死亡的主要病因.为控制EV71感染的流行,国内外均在开展不同种类EV71疫苗的研发,其中以灭活疫苗的进展最快,目前国内3家EV71全病毒灭活疫苗即将进入Ⅲ期临床试验阶段.本文就全病毒灭活疫苗的研发进展及质量控制和评价要点作一综述.

  15. 2013年云南省内地及边境地区健康儿童肠道病毒带毒调查研究%Molecular typing of enteroviruses isolated from healthy children in the interior and the border re-gions of Yunnan province in 2013

    Institute of Scientific and Technical Information of China (English)

    赵智娴; 丁峥嵘; 田炳均; 张杰; 汤晶晶

    2014-01-01

    -eight (6.27%) strains of EVs were isolated from 606 samples, and among them , fourteen strains were isolated from the interior region and the rest were isolated from the border region.Seven EVs positive strains (7/606, 1.16%) were polioviruses that were all identified as vac-cine strains.The rest thirty-one strains (31/606, 5.12%) were non-polio enteroviruses (NPEVs) that were all classified into human enterovirus B ( HEV-B) .No HEV-A and HEV-D viruses were detected .Conclu-sion The numbers of healthy children carrying EVs in the border region of Yunnan province were higher than that in the interior region in 2013 .HEV-B viruses were the predominant viruses as indicated in this study.No wild polioviruses were detected suggesting a sustained polio-free status in Yunnan province .The phylogenetic analysis showed that the isolated E 19 and CB3 viruses in Yunnan province presented diverse ge-netic characteristics .

  16. Metagenomics Study of Viral Pathogens in Undiagnosed Respiratory Specimens and Identification of Human Enteroviruses at a Thailand Hospital

    Science.gov (United States)

    Zhou, Yanfei; Fernandez, Stefan; Yoon, In-Kyu; Simasathien, Sriluck; Watanaveeradej, Veerachai; Yang, Yu; Marte-Salcedo, Omely A.; Shuck-Lee, Deidra J.; Thomas, Stephen J.; Hang, Jun; Jarman, Richard G.

    2016-01-01

    Numerous pathogens cause respiratory infections with similar symptoms. Routine diagnostics detect only a limited number of pathogens, leaving a gap in respiratory illness etiology surveillance. This study evaluated next-generation sequencing for unbiased pathogen identification. Respiratory samples collected in Thailand, Philippines, Bhutan, and Nepal, that were negative by several molecular and immunofluorescence assays, underwent viral cultivation. Samples which demonstrated cytopathic effect in culture (N = 121) were extracted and tested by Luminex xTAG respiratory viral panel (RVP) assay and deep sequencing by Roche 454 FLX Titanium system. Using RVP assay, 52 (43%) samples were positive for enterovirus or rhinovirus and another three were positive for respiratory syncytial virus B, parainfluenza 4, and adenovirus. Deep sequencing confirmed the Luminex assay results and identified additional viral pathogens. Human enteroviruses, including Enterovirus A type 71 and 12 types of Enterovirus B (EV-B) were identified from a hospital in Bangkok. Phylogenetic and recombination analysis showed high correlation of VP1 gene-based phylogeny with genome-wide phylogeny and the frequent genetic exchange among EV-B viruses. The high number and diversity of enteroviruses in the hospital in Bangkok suggests prevalent existence. The metagenomic approach used in our study enabled comprehensive diagnoses of respiratory viruses. PMID:27352877

  17. 肠道病毒71型的功能基因组学研究进展%Progress in the functional genomics researches on human enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    高爽; 龙健儿

    2012-01-01

    Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease (HFMD) in infant, also has been associated with neurological diseases including asepic meningitis, brain stem encephalitis and poliomyelitis-like paralysis. Here we focus on the progress in the research on EV71 genomic structure and function. Knowledge on EV71 functional genomics would be great helpful to development of antiviral drugs and vaccines.%肠道病毒71型(enterovirus type 71,EV71)感染通常引起婴幼儿手足口病(hand,foot and mouth disease,HFMD),但少数可引起无菌性脑膜炎(asepic meningitis)、脑炎(encephalitis)和类脊髓灰质炎的麻痹性疾病(poliomyelitis-like paralysis)等严重的神经系统疾病.功能基因组学研究对于探讨EV71的感染及复制过程、药物及疫苗的研制具有重大意义.该文就EV71的基因组结构及其功能的研究进展作简要的概述.

  18. A novel enterovirus and parechovirus multiplex one-step real-time PCR-validation and clinical experience

    DEFF Research Database (Denmark)

    Nielsen, A. C. Y.; Bottiger, B.; Midgley, S. E.

    2013-01-01

    and human parechovirus type 3 had a similar seasonal pattern with a peak during the summer and autumn. Human parechovirus type 3 was almost invariably found in children less than 4 months of age. In conclusion, a multiplex assay was developed allowing simultaneous detection of 2 viruses, which can cause......As the number of new enteroviruses and human parechoviruses seems ever growing, the necessity for updated diagnostics is relevant. We have updated an enterovirus assay and combined it with a previously published assay for human parechovirus resulting in a multiplex one-step RT-PCR assay....... The multiplex assay was validated by analysing the sensitivity and specificity of the assay compared to the respective monoplex assays, and a good concordance was found. Furthermore, the enterovirus assay was able to detect 42 reference strains from all 4 species, and an additional 9 genotypes during panel...

  19. 肠道病毒71型疫苗研究进展%Advances in research on enterovirus 71 vaccines

    Institute of Scientific and Technical Information of China (English)

    马洁; 邓永强; 秦成峰; 秦鄂德

    2015-01-01

    Enterovirus 71 (EV71) is one of the primary causative agents of hand, foot and mouth disease in children and closely associated with severe neurological complications and even deaths.EV71 outbreaks have occurred throughout the Asia-Pacific region since 1990s, posing global public health threat;however, no specific therapeutic strategy exists for severe EV71 infection.Several inactivated vaccine products have entered or finished the clinical trial stage, and some novel vaccine candidates, including live attenuated, subunit, and virus-like particle, show great potential for further develop-ment.This review summarizes the present situation and progress in the development of EV71 vaccines.%肠道病毒71型(enterovirus 71,EV71)是引起儿童手足口病的主要病原体之一,其感染可在少数患者中引起严重的神经系统综合征甚至导致死亡。自20世纪90年代后期在东南亚地区暴发以来,EV71感染已成为严重威胁全球,尤其是亚太地区儿童健康的公共卫生问题之一。尽管目前临床上尚无针对EV71的安全有效的疫苗,但多个灭活疫苗已进入或完成临床研究,减毒活疫苗、亚单位疫苗、病毒样颗粒疫苗等新型疫苗也显示出良好的发展前景,该文综述了EV71疫苗的最新研究进展。

  20. RNA interference against Enterovirus 71 replication%RNA干扰技术抗肠道病毒71型复制

    Institute of Scientific and Technical Information of China (English)

    李国栋; 杨倬; 张景海

    2013-01-01

    Objective To provide certain scientific basis to suppress Enterovirus 71 (EV 71) replication by RNA interference (RNAi). Methods RNA interference (RNAi) was used as a therapeutic approach to inhibit EV 71 replication in rhabdomyosarcoma(RD) cells. The inhibition effects were confirmed by a corresponding decrease in viral RNA of the infected cells,the expression level of viral protein and the number of progeny virus in the cultured supernatants. The inhibitory effect was validated through Western-blot, Real-time PCR and virus titer. Results The siRNAs targeting viral genome 5 'UTR and VP2 could effectively block viral replications. Conclusions This study confirms that RNAi method possesses potential and feasibility in the specific viral inhibition.%目的 肠道病毒71型(Enterovirus 71,EV 71)是手足口病(hand,foot and mouth disease,HFMD)主要的病原体之一.研究RNA干扰技术抑制肠道病毒71型复制.方法 以RNA干扰技术(RNAi)为干预手段,抑制病毒EV 71在人横纹肌肉瘤(rhabdomyosarcoma,RD)细胞中的复制.通过Western blot、Real-time PCR和病毒滴度3种方法验证,其抑制效果体现在感染细胞内部病毒RNA,病毒蛋白质的表达水平和培养基上清中子代病毒颗粒的数量上.结果 靶向病毒基因组5'UTR和VP2的siRNAs具有明显的病毒抑制效应.结论 此研究证实RNAi方法具有特异性抑制病毒复制的潜能和可行性.

  1. Complete genome analysis of the C4 subgenotype strains of enterovirus 71: predominant recombination C4 viruses persistently circulating in China for 14 years.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available Genetic recombination is a well-known phenomenon for enteroviruses. To investigate the genetic characterization and the potential recombination of enterovirus 71 (EV71 circulating in China, we determined the 16 complete genome sequences of EV71 isolated from Hand Foot Mouth Disease (HFMD patients during the large scale outbreak and non-outbreak years since 1998 in China. The full length genome sequences of 16 Chinese EV71 in present study were aligned with 186 genome sequences of EV71 available from GenBank, including 104 China mainland and 82 international sequences, covering the time period of 1970-2011. The oldest strains of each subgenotype of EV71 and prototype strains of HEV-A were included to do the phylogenetic and Simplot analysis. Phylogenetic analysis indicated that all Chinese strains were clustered into C4 subgenotype of EV71, except for HuB/CHN/2009 clustered into A and Xiamen/CHN/2009 clustered into B5 subgenotype. Most of C4 EV71 were clustered into 2 predominant evolutionary branches: C4b and C4a evolutionary brunches. Our comprehensive recombination analysis showed the evidence of genome recombination of subgenotype C4 (including C4a and C4b sequences between structural genes from genotype C EV71 and non-structural genes from the prototype strains of CAV16, 14 and 4, but the evidence of intratypic recombination between C4 strains and B subgenotype was not enough strong. This intertypic recombination C4 viruses were first seen in 1998 and became the predominant endemic viruses circulating in China mainland for at least 14 years. A shift between C4a and C4b evolutionary brunches of C4 recombination viruses were observed, and C4a viruses have been associated with large scale nationwide HFMD outbreak with higher morbidity and mortality since 2007.

  2. Inhibition of enterovirus 71-induced apoptosis by allophycocyanin isolated from a blue-green alga Spirulina platensis.

    Science.gov (United States)

    Shih, Shin-Ru; Tsai, Kun-Nan; Li, Yi-Shuane; Chueh, Chuang-Chun; Chan, Err-Cheng

    2003-05-01

    Enterovirus 71 infection causes significant morbidity and mortality in children, yet there is no effective treatment. In this study, a protein-bound pigment, allophycocyanin purified from blue-green algae is first reported to exhibit anti-enterovirus 71 activity. Allophycocyanin neutralized the enterovirus 71-induced cytopathic effect in both human rhabdomyosarcoma cells and African green monkey kidney cells. The 50% inhibitory concentration of allophycocyanin for neutralizing the enterovirus 71-induced cytopathic effect was approximately 0.045 +/- 0.012 microM in green monkey kidney cells. The cytotoxic concentrations of allophycocyanin for rhabdomyosarcoma cells and African green monkey kidney cells were 1.653 +/- 0.003 microM and 1.521 +/- 0.012 microM, respectively. A plaque reduction assay showed that the concentrations of allophycocyanin for reducing plaque formation by 50% were approximately 0.056 +/- 0.007 microM and 0.101 +/- 0.032 microM, when allophycocyanin were added at the state of viral adsorption and post-adsorption, respectively. Antiviral activity was more efficient in cultures treated with allophycocyanin before viral infection compared with that in the cultures treated after infection. Allophycocyanin was also able to delay viral RNA synthesis in the infected cells and to abate the apoptotic process in enterovirus 71-infected rhabdomyosarcoma cells with evidence of characteristic DNA fragmentation, decreasing membrane damage and declining cell sub-G1 phase. It is concluded that allophycocyanin possesses antiviral activity and has a potential for development as an anti-enterovirus 71 agent.

  3. EV71疫苗研究进展%Progress of reaseach on vaccine of Enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    刘刚; 姚昕; 李凤祥

    2009-01-01

    肠道病毒71型(EV71),可引起手足口病(HFMD)和严重神经系统疾病.近年来,在世界多个国家和地区报道了EV71的爆发.由于目前缺乏有效的抗病毒药物,因此研制有效的疫苗是控制EV71流行最为有效的策略.近年来很多报道显示在EV71疫苗研究上取得了重要进展,本文以此为重点概括了EV71灭活疫苗、重组疫苗、DNA疫苗、多肽疫苗、减毒活疫苗等以及动物模型方面的研究进展.%Enterovirus 71(EV71)is known to be a causative agent of hand-foot-mouth disease(HFMD)and severe neurological complications.Many Ev71 outbreaks have been reposed in different regions of the world.Due to the lack of an effective antiviralagent,primary prevention of the disease,including the development of effective vaccines,has been the top priority in terms of control strategies.Recently,many reports indicated lots of important progression is acquired.In this article,we renewed the progression of EV71 animal model and vaccines which inchded inactivation vaccine,recombinant vaccine,DNA vaccine,polypeptide vaccine and live attenuated vaccine.

  4. Antiviral Potential of a Novel Compound CW-33 against Enterovirus A71 via Inhibition of Viral 2A Protease

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    Ching-Ying Wang

    2015-06-01

    Full Text Available 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 IFN-β were evaluated by inhibitory assays of virus-induced apoptosis, plaque formation, and virus yield. CW-33 showed antiviral activities with an IC50 of near 200 µM in EV-A71 plaque reduction and virus yield inhibition assays. While, anti-EV-A71 activities of CW-33 combined with 100 U/mL IFN-β exhibited a synergistic potency with an IC50 of approximate 1 µM in plaque reduction and virus yield inhibition assays. Molecular docking revealed CW-33 binding to EV-A71 2A protease active sites, correlating with an inhibitory effect of CW33 on in vitro enzymatic activity of recombinant 2A protease IC50 = 53.1 µM. Western blotting demonstrated CW-33 specifically inhibiting 2A protease-mediated cleavage of IFNAR1. CW-33 also recovered Type I IFN-induced Tyk2 and STAT1 phosphorylation as well as 2',5'-OAS upregulation in EV-A71 infected cells. The results demonstrated CW-33 inhibiting viral 2A protease activity to reduce Type I IFN antagonism of EV-A71. Therefore, CW-33 combined with a low-dose of Type I IFN could be applied in developing alternative approaches to treat EV-A71 infection.

  5. A Novel Enterovirus 71 (EV71) Virulence Determinant: The 69th Residue of 3C Protease Modulates Pathogenicity

    Science.gov (United States)

    Li, Bingqing; Yue, Yingying; Zhang, Yajie; Yuan, Zenglin; Li, Peng; Song, Nannan; Lin, Wei; Liu, Yan; Gu, Lichuan; Meng, Hong

    2017-01-01

    Human enterovirus type 71 (EV71), the major causative agent of hand-foot-and-mouth disease, has been known to cause fatal neurological complications. Unfortunately, the reason for neurological complications that have been seen in fatal cases of the disease and the relationship between EV71 virulence and viral genetic sequences remains largely undefined. The 3C protease (3Cpro) of EV71 plays an irreplaceable role in segmenting the precursor polyprotein during viral replication, and intervening with host life activity during viral infection. In this study, for the first time, the 69th residue of 3C protease has been identified as a novel virulence determinant of EV71. The recombinant virus with single point variation, in the 69th of 3Cpro, exhibited obvious decline in replication, and virulence. We further determined the crystal structure of 3C N69D at 1.39 Ǻ resolution and found that conformation of 3C N69D demonstrated significant changes compared with a normal 3C protein, in the substrate-binding site and catalytic active site. Strikingly, one of the switch loops, essential in fixing substrates, adopts an open conformation in the 3C N69D-rupintrivir complex. Consistent with this apparent structural disruption, the catalytic activity of 3C N69D decreased sharply for host derived and viral derived substrates, detected for both in vitro and in vivo. Interestingly, in addition to EV71, Asp69 was also found in 3C proteases of other virus strains, such as CAV16, and was conserved in nearly all C type human rhinovirus. Overall, we identified a natural virulence determinant of 3C protease and revealed the mechanism of attenuated virulence is mediated by N69D substitution. Our data provides new insight into the enzymatic mechanism of a subdued 3C protease and suggests a theoretical basis for virulence determinantion of picornaviridae. PMID:28217559

  6. Display of VP1 on the surface of baculovirus and its immunogenicity against heterologous human enterovirus 71 strains in mice.

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    Tao Meng

    Full Text Available BACKGROUND: Human Enterovirus 71 (EV71 is a common cause of hand, foot and mouth disease (HFMD in young children. It is often associated with severe neurological diseases and has caused high mortalities in recent outbreaks across the Asia Pacific region. Currently, there is no effective vaccine and antiviral agents available against EV71 infections. VP1 is one of the major immunogenic capsid protein of EV71 and plays a crucial role in viral infection. Antibodies against VP1 are important for virus neutralization. METHODOLOGY/PRINCIPAL FINDING: In the present study, infectious EV71 viruses were generated from their synthetic complementary DNA using the human RNA polymerase I reverse genetics system. Secondly, the major immunogenic capsid protein (VP1 of EV71-Fuyang (subgenogroup C4 was displayed on the surface of recombinant baculovirus Bac-Pie1-gp64-VP1 as gp64 fusion protein under a novel White Spot Syndrome Virus (WSSV immediate early ie1 promoter. Baculovirus expressed VP1 was able to maintain its structural and antigenic conformity as indicated by immunofluorescence assay and western blot analysis. Interestingly, our results with confocal microscopy revealed that VP1 was able to localize on the plasma membrane of insect cells infected with recombinant baculovirus. In addition, we demonstrated with transmission electron microscopy that baculovirus successfully acquired VP1 from the insect cell membrane via the budding process. After two immunizations in mice, Bac-Pie1-gp64-VP1 elicited neutralization antibody titer of 1∶64 against EV71 (subgenogroup C4 in an in vitro neutralization assay. Furthermore, the antisera showed high cross-neutralization activities against all 11 subgenogroup EV71 strains. CONCLUSION: Our results illustrated that Bac-Pie1-gp64-VP1 retained native epitopes of VP1 and acted as an effective EV71 vaccine candidate which would enable rapid production without any biosafety concerns.

  7. The persistent circulation of enterovirus 71 in People's Republic of China: causing emerging nationwide epidemics since 2008.

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    Xiaojuan Tan

    Full Text Available Emerging epidemics of hand-foot-and-mouth disease (HFMD associated with enterovirus 71 (EV71 has become a serious concern in mainland China. It caused 126 and 353 fatalities in 2008 and 2009, respectively. The epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. To understand the virological evolution of this emerging outbreak, 326 VP1 gene sequences of EV71 detected in China from 1987 to 2009 were collected for genetic analyses. Evidence from both traditional and molecular epidemiology confirmed that the recent HFMD outbreak was an emerging one caused by EV71 of subgenotype C4. This emerging HFMD outbreak is associated with EV71 of subgenotype C4, circulating persistently in mainland China since 1998, but not attributed to the importation of new genotype. Originating from 1992, subgenotype C4 has been the predominant genotype since 1998 in mainland China, with an evolutionary rate of 4.6∼4.8×10⁻³ nucleotide substitutions/site/year. The phylogenetic analysis revealed that the majority of the virus during this epidemic was the most recent descendant of subgenotype C4 (clade C4a. It suggests that the evolution might be one of the potential reasons for this native virus to cause the emerging outbreak in China. However, strong negative selective pressure on VP1 protein of EV71 suggested that immune escape might not be the evolving strategy of EV71, predicting a light future for vaccine development. Nonetheless, long-term antigenic and genetic surveillance is still necessary for further understanding.

  8. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome

    Science.gov (United States)

    Fowler III, Alpha A; Kim, Christin; Lepler, Lawrence; Malhotra, Rajiv; Debesa, Orlando; Natarajan, Ramesh; Fisher, Bernard J; Syed, Aamer; DeWilde, Christine; Priday, Anna; Kasirajan, Vigneshwar

    2017-01-01

    We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth University with vitamin C and with the very positive results of a previously performed phase I safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation (ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient’s recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes. PMID:28224112

  9. Co-circulation and evolution of polioviruses and species C enteroviruses in a district of Madagascar.

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    Mala Rakoto-Andrianarivelo

    2007-12-01

    Full Text Available Between October 2001 and April 2002, five cases of acute flaccid paralysis (AFP associated with type 2 vaccine-derived polioviruses (VDPVs were reported in the southern province of the Republic of Madagascar. To determine viral factors that favor the emergence of these pathogenic VDPVs, we analyzed in detail their genomic and phenotypic characteristics and compared them with co-circulating enteroviruses. These VDPVs appeared to belong to two independent recombinant lineages with sequences from the type 2 strain of the oral poliovaccine (OPV in the 5'-half of the genome and sequences derived from unidentified species C enteroviruses (HEV-C in the 3'-half. VDPV strains showed characteristics similar to those of wild neurovirulent viruses including neurovirulence in poliovirus-receptor transgenic mice. We looked for other VDPVs and for circulating enteroviruses in 316 stools collected from healthy children living in the small area where most of the AFP cases occurred. We found vaccine PVs, two VDPVs similar to those found in AFP cases, some echoviruses, and above all, many serotypes of coxsackie A viruses belonging to HEV-C, with substantial genetic diversity. Several coxsackie viruses A17 and A13 carried nucleotide sequences closely related to the 2C and the 3D(pol coding regions of the VDPVs, respectively. There was also evidence of multiple genetic recombination events among the HEV-C resulting in numerous recombinant genotypes. This indicates that co-circulation of HEV-C and OPV strains is associated with evolution by recombination, resulting in unexpectedly extensive viral diversity in small human populations in some tropical regions. This probably contributed to the emergence of recombinant VDPVs. These findings give further insight into viral ecosystems and the evolutionary processes that shape viral biodiversity.

  10. Rupintrivir is a promising candidate for treating severe cases of Enterovirus-71 infection

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the suitability of rupintrivir against Enterovirus 71(EV71)induced severe clinical symptoms using computational methods. METHODS:The structure of EV71 3C protease was predicted by homology modeling.The binding free energies between rupintrivir and EV71 3C and human rhinovirus 3C protease were computed by molecular dynamics and molecular mechanics Poisson-Boltzmann/ surface area and molecular mechanics generalized-born/ surface area methods.EV71 3C fragments obtained from clinical samples col...

  11. Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein.

    Science.gov (United States)

    van der Schaar, H M; Melia, C E; van Bruggen, J A C; Strating, J R P M; van Geenen, M E D; Koster, A J; Bárcena, M; van Kuppeveld, F J M

    2016-01-01

    Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for

  12. Coxsackievirus A6 and hand, foot, and mouth disease, Finland.

    Science.gov (United States)

    Osterback, Riikka; Vuorinen, Tytti; Linna, Mervi; Susi, Petri; Hyypiä, Timo; Waris, Matti

    2009-09-01

    During fall 2008, an outbreak of hand, foot, and mouth disease (HFMD) with onychomadesis (nail shedding) as a common feature occurred in Finland. We identified an unusual enterovirus type, coxsackievirus A6 (CVA6), as the causative agent. CVA6 infections may be emerging as a new and major cause of epidemic HFMD.

  13. ONYCHOMADESIS IN A CHILD - SEQUELAE OF HAND - FOOT - MOUTH DISEASE

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    Adhikrishnan

    2015-04-01

    Full Text Available Hand – Foot – Mouth disease of coxsackie a virus and Enteroviruses. With symptoms like fever, sore throat, followed by Maculopapular and vesicular lesions around the oral cavity, palms and soles and recently adding to the list is onychomadesis. As a result of nail matrix function arrest, there is transverse ridging (beau’s lines, temporary loss of nail plate.

  14. Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children.

    Science.gov (United States)

    Zhang, Ying; Wang, Lichun; Liao, Yun; Liu, Longding; Ma, Kaili; Yang, Erxia; Wang, Jingjing; Che, Yanchun; Jiang, Li; Pu, Jing; Guo, Lei; Feng, Min; Liang, Yan; Cui, Wei; Yang, Huai; Li, Qihan

    2015-11-17

    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. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine.

  15. Evolutionary genetics of human enterovirus 71: origin, population dynamics, natural selection, and seasonal periodicity of the VP1 gene.

    Science.gov (United States)

    Tee, Kok Keng; Lam, Tommy Tsan-Yuk; Chan, Yoke Fun; Bible, Jon M; Kamarulzaman, Adeeba; Tong, C Y William; Takebe, Yutaka; Pybus, Oliver G

    2010-04-01

    Human enterovirus 71 (EV-71) is one of the major etiologic causes of hand, foot, and mouth disease (HFMD) among young children worldwide, with fatal instances of neurological complications becoming increasingly common. Global VP1 capsid sequences (n = 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods. We estimated that the common ancestor of human EV-71 likely emerged around 1941 (95% confidence interval [CI], 1929 to 1952), subsequently diverging into three genogroups: B, C, and the now extinct genogroup A. Genealogical analysis revealed that diverse lineages of genogroup B and C (subgenogroups B1 to B5 and C1 to C5) have each circulated cryptically in the human population for up to 5 years before causing large HFMD outbreaks, indicating the quiescent persistence of EV-71 in human populations. Estimated phylogenies showed a complex pattern of spatial structure within well-sampled subgenogroups, suggesting endemicity with occasional lineage migration among locations, such that past HFMD epidemics are unlikely to be linked to continuous transmission of a single strain of virus. In addition, rises in genetic diversity are correlated with the onset of epidemics, driven in part by the emergence of novel EV-71 subgenogroups. Using subgenogroup C1 as a model, we observe temporal strain replacement through time, and we investigate the evidence for positive selection at VP1 immunogenic sites. We discuss the consequences of the evolutionary dynamics of EV-71 for vaccine design and compare its phylodynamic behavior with that of influenza virus.

  16. Inhibition of enterovirus 71 (EV-71 infections by a novel antiviral peptide derived from EV-71 capsid protein VP1.

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    Chee Wah Tan

    Full Text Available Enterovirus 71 (EV-71 is the main causative agent of hand, foot and mouth disease (HFMD. In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50 values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.

  17. Epidemiological, molecular and clinical features of Enterovirus 109 infection in children and in adult stem cell transplant recipients

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    Debiaggi Maurizia

    2012-09-01

    Full Text Available Abstract Background A novel human enterovirus (HEV type within the species HEV-C, named EV109, was discovered from cases of respiratory illness in Nicaragua in September 2010. The aim of this study, was to retrospectively examine the presence and the role of EV109 in respiratory samples from two patients populations; infants below the age of 2 years, hospitalized for acute respiratory diseases (ARDs and adult hematopoietic stem cell transplantation recipients. Results A total of 1149 nasopharingeal aspirates were collected and tested for the presence of EV109 by reverse transcription-PCR (RT-PCR. In positive samples, the presence of the most common respiratory viruses was also assayed and clinical symptoms were evaluated. Samples from 2 of the 974 infants tested positive for EV109 RNA (0.2% and belonged to patients with lower ARDs; co-infection with other viral pathogens under study was observed in both cases. In transplant recipients, one out of the 175 samples analyzed, from a patients with upper respiratory simptoms tested positive for HEV 109 in the absence of co-infecting viruses. Sequence analysis of amplified EV109 genomic regions, showed only a few nucleotide differences when compared with the Nicaraguan strains. Conclusions Overall these results indicate that HEV109 variants have circulated and differentiated in different lineages worldwide. Although more cases and larger studies are needed, HEV109 infection may be associated to ARDs both in infants and in hematopoietic stem cell transplantation recipients. If these preliminary observations will be confirmed, improved molecular methods with a wider panel of potential pathogens will be useful for monitoring these categories of patients.

  18. Population dynamics and genetic diversity of C4 strains of human enterovirus 71 in Mainland China, 1998-2010.

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    Dawei Guan

    Full Text Available BACKGROUND: Since 1997, several countries within the Asian Pacific region have been affected by one or more massive outbreaks of Hand Foot and Mouth Disease (HFMD. Virus typing experiments revealed that these outbreaks were caused by strains of human enterovirus 71 (EV71 belonging to several different, recently emerged subgenogroups. In mainland China, a different situation was observed. The first outbreak, localized in Shangdong Province, was reported in 2007, and was followed by a wide-spread outbreak in mainland China in 2008. Since then, numbers of reported HFMD cases have been persistently high. METHODOLOGY/PRINCIPAL FINDINGS: To gain insight in the epidemiological behavior of EV71 in China, we studied genetic diversity and EV71 population dynamics to address whether the increase in number of reported EV71 infections reflects a real increase in viral spread or is just the result of increased awareness and surveillance. We used systematically collected VP1 gene sequences of 257 EV71 strains collected in Guangdong province from 2008 to 2010 as part of HFMD surveillance activities, and supplemented them with 305 GenBank EV71 reference stains collected in China from 1998 to 2010. All isolates from Guangdong Province belonged to subgenogroup C4. Viral population dynamics indicated that the increased reporting of HFMD in China since 2007 reflects a real increase in viral spread and continued replacement of viral lineages through time. Amino acid sequence comparisons revealed substitution of amino acid in residues 22, 145 and 289 through time regularly with the VP1 gene of EV71 strains isolated in mainland China from 1998 to 2010. CONCLUSIONS: EV71 strains isolated in mainland China mainly belonged to subgenogroup C4. There was exponential growth of the EV71 virus population in 2007 and 2008. There was amino acid substitution through time regularly with the VP1 gene which possibly increased viral spread and/or ability of the virus to circulate

  19. Signifiance of Arginine 20 in the 2A protease for swine vesicular disease virus pathogenicity

    DEFF Research Database (Denmark)

    Inoue, Toru; Zhang, Zhidong; Wang, Leyuan

    2007-01-01

    Pathogenic and attenuated strains of swine vesicular disease virus (SVDV), an enterovirus, have been characterized previously and, by using chimeric infectious cDNA clones, the key determinants of pathogenicity in pigs have been mapped to the coding region for 1D–2A. Within this region, residue 20...... and appearance of significant disease....

  20. Viral meningitis epidemics and a single, recent, recombinant and anthroponotic origin of swine vesicular disease virus

    DEFF Research Database (Denmark)

    Bruhn, Christian Anders Wathne; Nielsen, Sandra Cathrine Abel; Samaniego Castruita, Jose Alfredo

    2015-01-01

    BACKGROUND AND OBJECTIVES: Swine vesicular disease virus (SVDV) is a close relative of the human Enterovirus B serotype, coxsackievirus B5. As the etiological agent of a significant emergent veterinary disease, several studies have attempted to explain its origin. However, several key questions...

  1. Progress in research on enterovirus 71 pathogenesis%肠道病毒71致病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    任倩; 马丽霞; 张乐海

    2011-01-01

    肠道病毒71(EV71)是引起手足口病(HFMD)的主要病原体之一,同时也是肠道病毒属中能引起无菌性脑膜炎、脑炎和脊髓灰质炎样麻痹等多种神经系统相关疾病的一种病原体.20世纪90年代后期以来,EV71在亚太地区多次流行,期间有很多关于该病毒引起的婴幼儿神经源性肺水肿病例及死亡病例的报道,引起了人们的高度重视.因此,阐明EV71的致病机制对于该病的预防和治疗至关重要.此文对病毒结构蛋白、非结构蛋白、病毒结合蛋白、受体及信号调节因子等方面与致病机制的关系进行分析,以期对EV71的致病机制有更深刻地理解,从而为有效的疫苗和药物研制提供新的思路.%Enterovirus 71 (EV71) is one of the major pathogenesis to cause hand, foot and mouth disease (HFMD) . EV71 is also one of the pathogeneses in enteroviruses, which can cause nervous system related disease such as aseptic meningitis, encephalitis and poliomyelitis-like paralysis. Since the late 1990s, there has been many epidemic activities throughout the Asia-Pacific region caused by EV71 and many reports about the infant neurotoxicity infections and deaths cases, and it has been paid great attention. Therefore, it is very important for the prevention and treatment of this disease to expound the pathogenesis of the diseases caused by EV71. This article focuses on the relations between virus structural proteins, non-structural proteins, virus binding proteins, receptors and signal regulating factors. It is helpful for further understanding about the pathogenesis and providing a new thinking to prepare the effective vaccines and drugs.

  2. Mutations in the nonstructural protein 3A confer resistance to the novel enterovirus replication inhibitor TTP-8307.

    NARCIS (Netherlands)

    Palma, A.M. De; Thibaut, H.J.; Linden, L. van de; Lanke, K.H.W.; Heggermont, W.; Ireland, S.; Andrews, R.; Arimilli, M.; Al-Tel, T.H.; Clercq, E. De; Kuppeveld, F.J.M. van; Neyts, J.

    2009-01-01

    A novel compound, TTP-8307, was identified as a potent inhibitor of the replication of several rhino- and enteroviruses. TTP-8307 inhibits viral RNA synthesis in a dose-dependent manner, without affecting polyprotein synthesis and/or processing. Drug-resistant variants of coxsackievirus B3 were all

  3. Novel Substituted Heteroaromatic Piperazine and Piperidine Derivatives as Inhibitors of Human Enterovirus 71 and Coxsackievirus A16

    Directory of Open Access Journals (Sweden)

    Xian Zhang

    2013-04-01

    Full Text Available A series of substituted heteroaromatic piperazine and piperidine derivatives were found through virtual screening based on the structure of human enterovirus 71 capsid protein VP1. The preliminary biological evaluation revealed that compounds 8e and 9e have potent activity against EV71 and Coxsackievirus A16 with low cytotoxicity.

  4. Polymorphisms in the innate immune IFIH1 gene, frequency of enterovirus in monthly fecal samples during infancy, and islet autoimmunity

    DEFF Research Database (Denmark)

    Witsø, Elisabet; Tapia, German; Cinek, Ondrej

    2011-01-01

    autoimmunity reported in our previous study was not materially influenced by the IFIH1 SNPs.We conclude that the type 1 diabetes-associated IFIH1 polymorphisms have no, or only minor influence on the occurrence, quantity or duration of enterovirus infection in the gut. Its effect on the risk of diabetes...

  5. Complete Genome Sequences of Nine Enterovirus D68 Strains from Patients of the Lower Hudson Valley, New York, 2016

    Science.gov (United States)

    Huang, Weihua; Yin, Changhong; Zhuge, Jian; Farooq, Taliya; Yoon, Esther C.; Nolan, Sheila M.; Chen, Donald; Fallon, John T.

    2016-01-01

    Complete genome sequences of nine enterovirus D68 (EV-D68) strains from patients in New York were obtained in 2016 by metagenomic next-generation sequencing. Comparative genomic analysis suggests that a new subclade B3, with ~4.5% nucleotide divergence from subclade B1 strains causing the 2014 outbreak, is circulating in the United States in 2016. PMID:27979945

  6. [Specific clinical, epidemiological patterns and laboratory diagnostics of enterovirus infection in the Republic of Belarus].

    Science.gov (United States)

    Amvros'eva, T V; Poklonskaia, N V; Bogush, Z F; Kazinets, O N; Germanovich, F A; Fisenko, E G; Titov, L P; Kvacheva, Z B; Bezruchko, A A; Scheslenok, E P

    2005-01-01

    The clinical and epidemiological patterns as well as the results of the laboratory verification of the outbreak of enterovirus infection (EVI) in Minsk during the period of summer-autumn, 2000, are presented. During this outbreak a variety of clinical forms were observed, the serous meningitis being prevalent (57.5%). Practically simultaneous occurrence of infection on the territory of all administrative districts of the city, the predominant involvement of children aged up to 14 years into the outbreak, a high proportion of simultaneous casualities in the multiple foci. A number of circulating enteroviruses (EV)--ECHO 30, ECHO 6 of three serotypes and Coxsackie B5--were simultaneously isolated from clinical material. EV of the same serotypes were isolated from tap drinking water, and neutralizing antibodies to these serotypes were often detected in the patients blood sera. Infectious EV were also present in samples of bottled water and in water reservoirs used for bathing. The routes of EV transmission and the improvement of EVI control are discussed.

  7. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly.

    Science.gov (United States)

    Wang, Robert Y L; Kuo, Rei-Lin; Ma, Wei-Chieh; Huang, Hsing-I; Yu, Jau-Song; Yen, Sih-Min; Huang, Chi-Ruei; Shih, Shin-Ru

    2013-09-01

    Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone.

  8. Phylogenetic evidence for multiple intertypic recombinations in enterovirus B81 strains isolated in Tibet, China.

    Science.gov (United States)

    Hu, Lan; Zhang, Yong; Hong, Mei; Zhu, Shuangli; Yan, Dongmei; Wang, Dongyan; Li, Xiaolei; Zhu, Zhen; Tsewang; Xu, Wenbo

    2014-08-12

    Enterovirus B81 (EV-B81) is a newly identified serotype within the species enterovirus B (EV-B). To date, only eight nucleotide sequences of EV-B81 have been published and only one full-length genome sequence (the prototype strain) has been made available in the GenBank database. Here, we report the full-length genome sequences of two EV-B81 strains isolated in the Tibet Autonomous Region of China during acute flaccid paralysis surveillance activities, and we also conducted an antibody seroprevalence study in two prefectures of Tibet. The sequence comparison and phylogenetic dendrogram analysis revealed high variability among the global EV-B81 strains and frequent intertypic recombination in the non-structural protein region of EV-B serotypes, suggesting high genetic diversity of EV-B81. However, low positive rates and low titers of neutralizing antibodies against EV-B81 were detected. Nearly 68% of children under the age of five had no neutralizing antibodies against EV-B81. Hence, the extent of transmission and the exposure of the population to this EV type are very limited. Although little is known about the biological and pathogenic properties of EV-B81 because of few research in this field owing to the limited number of isolates, our study provides basic information for further studies of EV-B81.

  9. Large outbreak of herpangina in children caused by enterovirus in summer of 2015 in Hangzhou, China

    Science.gov (United States)

    Li, Wei; Gao, Hui-hui; Zhang, Qiong; Liu, Yu-jie; Tao, Ran; Cheng, Yu-ping; Shu, Qiang; Shang, Shi-qiang

    2016-01-01

    Herpangina, usually caused by coxsackie virus A, is prevalent in children spreading through the fecal-oral transmission and the respiratory droplets dissemination. Also, it is mostly asymptomatic and self-limiting. In our study, we found that large outbreak of herpangina in children occurred in the summer of 2015 in Hangzhou, China. From May 1th to August 31th, a total of 10 210 children were diagnosed with herpangina in Children’s Hospital of Zhejiang University School of Medicine. 2 310 throat swabs were collected and tested for enterovirus detection by real-time RT-PCR, while 1 651 cases were positive with the rate of 71.5%. Based on VP1 gene or 5′UTR region sequences, Coxsackievirus A2, A4, A6, A10, B2, B4 and echovirus 30 were detected in these cases. More importantly, Coxsackievirus A2 may be the major subtype of enterovirus resulting in children with herpangina in hangzhou, China. PMID:27752104

  10. Heat shock protein-90-beta facilitates enterovirus 71 viral particles assembly

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Robert Y.L., E-mail: yuwang@mail.cgu.edu.tw [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Kuo, Rei-Lin [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Ma, Wei-Chieh [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Hsing-I [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yu, Jau-Song [Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Tao-Yuan 333, Taiwan (China); Yen, Sih-Min [Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Huang, Chi-Ruei [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333 Taiwan (China); Shih, Shin-Ru [Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China); Department of Medical Biotechnology and Laboratory Science and Graduate Program of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan (China)

    2013-09-01

    Molecular chaperones are reported to be crucial for virus propagation, but are not yet addressed in Human Enterovirus 71 (EV71). Here we describe the specific association of heat shock protein-90-beta (Hsp90β), but not alpha form (Hsp90α), with EV71 viral particles by the co-purification with virions using sucrose density gradient ultracentrifugation, and by the colocalization with viral particles, as assessed by immunogold electron microscopy. The reduction of the Hsp90β protein using RNA interference decreased the correct assembly of viral particles, without affecting EV71 replication levels. Tracking ectopically expressed Hsp90β protein associated with EV71 virions revealed that Hsp90β protein was transmitted to new host cells through its direct association with infectious viral particles. Our findings suggest a new antiviral strategy in which extracellular Hsp90β protein is targeted to decrease the infectivity of EV71 and other enteroviruses, without affecting the broader functions of this constitutively expressed molecular chaperone. - Highlights: • Hsp90β is associated with EV71 virion and is secreted with the release virus. • Hsp90β effects on the correct assembly of viral particles. • Viral titer of cultured medium was reduced in the presence of geldanamycin. • Viral titer was also reduced when Hsp90β was suppressed by siRNA treatment. • The extracellular Hsp90β was also observed in other RNA viruses-infected cells.

  11. Enterovirus-71 genotype C isolated in Peru between 2006 and 2009.

    Science.gov (United States)

    Huaman, Jose L; Carrion, Gladys; Ampuero, Julia S; Ocaña, Victor; Laguna-Torres, V Alberto; Hontz, Robert D

    2016-12-01

    Enterovirus-71 (EV71) was first isolated in California, United States in 1969, belongs to the genus Enterovirus, family Picornaviridae. Although infection normally causes mild, often undiagnosed illness, it can cause central nervous system infections that could turn fatal. Based on VP1 gene analysis, EV71 has been classified into six separate genotypes. Although the molecular epidemiology of EV71 has been well described via studies originating from Asia and Europe, it is mostly unknown in South America. From our study, four EV71 isolates from Peru were characterized using phylogenetic methods to determine their relationship with known reference strains. These four Peruvian EV71 isolates from between 2006 and 2009 were analyzed by RT-PCR using primers capable of amplifying the entire VP1 gene. Reference strains representing all six known genotypes were used to determine any recognizable phylogenetic relationships. In fact, all of our isolates clustered together within the genotype C1 lineage- separate from Asian, European, North American, and Australian strains. We present evidence that EV71 genotype C1 exists in Peru, and this is the first such report documenting EV71 genotype C1 circulating in South America. Gathering additional isolates will help elucidate a more complete global epidemiological picture of EV71 infections.

  12. Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014

    Science.gov (United States)

    Messacar, Kevin; Pastula, Daniel M.; Robinson, Christine C.; Leshem, Eyal; Sejvar, James J.; Nix, W. Allan; Oberste, M. Steven; Feikin, Daniel R.; Dominguez, Samuel R.

    2016-01-01

    During August 8, 2014–October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case–control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non–EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis. PMID:27434186

  13. Yakammaoto inhibits enterovirus 71 infection by reducing viral attachment, internalization, replication, and translation

    Directory of Open Access Journals (Sweden)

    Chia-Feng Yeh

    2015-06-01

    Full Text Available 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 antiviral activity against coxsackievirus B4 (CVB4. CVB4 and EV71 are enteroviruses. In this study, we evaluated the antiviral activity of hot water extract of yakammaoto against EV71. The results of plaque reduction assay and flow cytometry demonstrated that yakammaoto dose dependently inhibited EV71 infection. In addition, reverse transcription-polymerase chain reaction (RT-PCR and quantitative RT-PCR results showed that yakammaoto reduced viral replication. Western blotting analysis showed that yakammaoto can inhibit viral protein production. Thus, our results suggest that yakammaoto should be considered to manage EV71 infection in the future.

  14. Enterovirus no polio de casos con parálisis residual. Colombia, 1992-1995

    Directory of Open Access Journals (Sweden)

    Dioselina Peláez

    1999-06-01

    Full Text Available Las parálisis fláccidas agudas (PFA tienen una amplia variedad de orígenes y de agentes causales: físicos, fisiopatológicos, tóxicos e infecciosos. Entre estos últimos, el virus salvaje (silvestre de la poliomielitis y el enterovirus 71 (EV71, parecen ser los agentes virales más frecuentes. Habiendo eliminado el poliovirus salvaje autóctono como agente causal de enfermedad paralítica en Colombia desde junio de 1991 y teniendo aislamientos de virus no polio en el 20,8% del total de casos de PFA notificados anualmente, quisimos conocer el papel que juegan los enterovirus en la incidencia de parálisis fláccida aguda y la dinámica de circulación y distribución de los mismos en Colombia. Se revisó la base de datos de los casos notificados al Programa de Erradicación de la Poliomielitis en Colombia entre el 1"" de enero de 1992 y el 31 de diciembre de 1995, al cual se notificaron 856 casos sospechosos de niños menores de 15 años, y se escogieron 69 casos para el estudio pero se recuperaron 57 aislamientos virales por reinoculación en células RD y Hep-2C. Estos se identificaron mediante neutralización con mezclas de antisueros de Lim & Benyesh-Melnick (LBM.Todos ellos fueron sometidos a caracterización molecular mediante reacción en cadena de la polimerasa -PCR-, utilizando iniciadores complementarios a la regiónVP1 del genoma viral, seguida del análisis de secuencia de nucleótidos de los fragmentos amplificados por PCR. La identificación final del serotipo se realizó por comparación de nucleótidos en auto assemblery el análisis descriptivo de los datos. No se estableció circulación mayor de ningún serotipo específico en región geográfica alguna del país. Tampoco hubo asociación causal a ninguna patología característica con ninguno de los enterovirus aislados. Se describe el hallazgo de EV71 en un caso de PFA con diagnóstico clínico de síndrome de Guillain-Barré. La descripción de 22 serotipos diferentes

  15. Conjunctivitis (Pink Eye) in Newborns

    Science.gov (United States)

    ... Work Adenovirus Non-Polio Enterovirus Parent Portal Conjunctivitis (Pink Eye) in Newborns Language: English Español (Spanish) Recommend ... recién nacidos Newborns with symptoms of conjunctivitis (pink eye) should see a doctor right away. Neonatal ...

  16. Molecular epidemiology and evolution of human enterovirus serotype 68 in Thailand, 2006-2011.

    Directory of Open Access Journals (Sweden)

    Piyada Linsuwanon

    Full Text Available BACKGROUND: Publications worldwide have reported on the re-occurrence of human enterovirus 68 (EV68, a rarely detected pathogen usually causing respiratory illness. However, epidemiological data regarding this virus in particular on the Asian continent has so far been limited. METHODOLOGY/FINDINGS: We investigated the epidemiology and genetic variability of EV68 infection among Thai children with respiratory illnesses from 2006-2011 (n = 1810. Semi-nested PCR using primer sets for amplification of the 5'-untranslated region through VP2 was performed for rhino-enterovirus detection. Altogether, 25 cases were confirmed as EV68 infection indicating a prevalence of 1.4% in the entire study population. Interestingly, the majority of samples were children aged >5 years (64%. Also, co-infection with other viruses was found in 28%, while pandemic H1N1 influenza/2009 virus was the most common co-infection. Of EV68-positive patients, 36% required hospitalizations with the common clinical presentations of fever, cough, dyspnea, and wheezing. The present study has shown that EV68 was extremely rare until 2009 (0.9%. An increasing annual prevalence was found in 2010 (1.6% with the highest detection frequency in 2011 (4.3%. Based on analysis of the VP1 gene, the evolutionary rate of EV68 was estimated at 4.93 × 10(-3 substitutions/site/year. Major bifurcation of the currently circulating EV68 strains occurred 66 years ago (1945.31 with (1925.95-1960.4695% HPD. Among the current lineages, 3 clusters of EV68 were categorized based on the different molecular signatures in the BC and DE loops of VP1 combined with high posterior probability values. Each cluster has branched off from their common ancestor at least 36 years ago (1975.78 with (1946.13-1984.9795% HPD. CONCLUSION: Differences in epidemiological characteristic and seasonal profile of EV68 have been found in this study. Results from Bayesian phylogenetic investigations also revealed that EV68 should be

  17. Inactivation of a bovine enterovirus and a bovine parvovirus in cattle manure by anaerobic digestion, heat treatment, gamma irradiation, ensilage and composting

    Energy Technology Data Exchange (ETDEWEB)

    Monteith, H.D.; Shannon, E.E.; Derbyshire, J.B.

    1986-08-01

    A bovine enterovirus and a bovine parvovirus seeded into liquid cattle manure were rapidly inactivated by anaerobic digestion under thermophilic conditions (55/sup 0/C), but the same viruses survived for up to 13 and 8 days respectively under mesophilic conditions (35/sup 0/C). The enterovirus was inactivated in digested liquid manure heated to 70/sup 0/C for 30 min, but the parvovirus was not inactivated by this treatment. The enterovirus, seeded into single cell protein (the solids recovered by centrifugation of digested liquid manure), was inactivated by a gamma irradiation dose of 1.0 Mrad, but the parvovirus survived this dose. When single cell protein seeded with bovine enterovirus or bovine parvovirus was ensiled with cracked corn, the enterovirus was inactivated after a period of 30 days, while the parvovirus survived for 30 days in one of two experiments. Neither the enterovirus nor the parvovirus survived composting for 28 days in a thermophilic aerobic environment when seeded into the solid fraction of cattle manure. It was concluded that, of the procedures tested, only anaerobic digestion under thermophilic conditions appeared to be reliable method of viral inactivation to ensure the safety of single cell protein for refeeding to livestock. Composting appeared to be a suitable method for the disinfection of manure for use as a soil conditioner.

  18. The inactivation of a bovine enterovirus and a bovine parvovirus in cattle manure by anaerobic digestion, heat treatment, gamma irradiation, ensilage and composting.

    Science.gov (United States)

    Monteith, H D; Shannon, E E; Derbyshire, J B

    1986-08-01

    A bovine enterovirus and a bovine parvovirus seeded into liquid cattle manure were rapidly inactivated by anaerobic digestion under thermophilic conditions (55 degrees C), but the same viruses survived for up to 13 and 8 days respectively under mesophilic conditions (35 degrees C). The enterovirus was inactivated in digested liquid manure heated to 70 degrees C for 30 min, but the parvovirus was not inactivated by this treatment. The enterovirus, seeded into single cell protein (the solids recovered by centrifugation of digested liquid manure), was inactivated by a gamma irradiation dose of 1.0 Mrad, but the parvovirus survived this dose. When single cell protein seeded with bovine enterovirus or bovine parvovirus was ensiled with cracked corn, the enterovirus was inactivated after a period of 30 days, while the parvovirus survived for 30 days in one of two experiments. Neither the enterovirus nor the parvovirus survived composting for 28 days in a thermophilic aerobic environment when seeded into the solid fraction of cattle manure. It was concluded that, of the procedures tested, only anaerobic digestion under thermophilic conditions appeared to be reliable method of viral inactivation to ensure the safety of single cell protein for refeeding to livestock. Composting appeared to be a suitable method for the disinfection of manure for use as a soil conditioner.

  19. Near-complete genome sequencing of swine vesicular disease virus using the Roche GS FLX sequencing platform

    DEFF Research Database (Denmark)

    Nielsen, Sandra Cathrine Abel; Bruhn, Christian Anders Wathne; Samaniego Castruita, Jose Alfredo

    2014-01-01

    Swine vesicular disease virus (SVDV) is an enterovirus that is both genetically and antigenically closely related to human coxsackievirus B5 within the Picornaviridae family. SVDV is the causative agent of a highly contagious (though rarely fatal) vesicular disease in pigs. We report a rapid method...

  20. Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark

    DEFF Research Database (Denmark)

    Sørup, Signe; Stensballe, Lone G; Krause, Tyra G;

    2016-01-01

    with inactivated diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) or live measles-mumps-rubella vaccine (MMR) as their most recent vaccine. Methods.  A nationwide, register-based, retrospective cohort study of 137 403 Danish children born 1997-1999, who had received 3 doses...

  1. The enterovirus 71 A-particle forms a gateway to allow genome release: a cryoEM study of picornavirus uncoating.

    Directory of Open Access Journals (Sweden)

    Kristin L Shingler

    2013-03-01

    Full Text Available Since its discovery in 1969, enterovirus 71 (EV71 has emerged as a serious worldwide health threat. This human pathogen of the picornavirus family causes hand, foot, and mouth disease, and also has the capacity to invade the central nervous system to cause severe disease and death. Upon binding to a host receptor on the cell surface, the virus begins a two-step uncoating process, first forming an expanded, altered "A-particle", which is primed for genome release. In a second step after endocytosis, an unknown trigger leads to RNA expulsion, generating an intact, empty capsid. Cryo-electron microscopy reconstructions of these two capsid states provide insight into the mechanics of genome release. The EV71 A-particle capsid interacts with the genome near the icosahedral two-fold axis of symmetry, which opens to the external environment via a channel ∼10 Å in diameter that is lined with patches of negatively charged residues. After the EV71 genome has been released, the two-fold channel shrinks, though the overall capsid dimensions are conserved. These structural characteristics identify the two-fold channel as the site where a gateway forms and regulates the process of genome release.

  2. Enterovirus 71 VP1 activates calmodulin-dependent protein kinase II and results in the rearrangement of vimentin in human astrocyte cells.

    Directory of Open Access Journals (Sweden)

    Cong Haolong

    Full Text Available Enterovirus 71 (EV71 is one of the main causative agents of foot, hand and mouth disease. Its infection usually causes severe central nervous system diseases and complications in infected infants and young children. In the present study, we demonstrated that EV71 infection caused the rearrangement of vimentin in human astrocytoma cells. The rearranged vimentin, together with various EV71 components, formed aggresomes-like structures in the perinuclear region. Electron microscopy and viral RNA labeling indicated that the aggresomes were virus replication sites since most of the EV71 particles and the newly synthesized viral RNA were concentrated here. Further analysis revealed that the vimentin in the virus factories was serine-82 phosphorylated. More importantly, EV71 VP1 protein is responsible for the activation of calmodulin-dependent protein kinase II (CaMK-II which phosphorylated the N-terminal domain of vimentin on serine 82. Phosphorylation of vimentin and the formation of aggresomes were required for the replication of EV71 since the latter was decreased markedly after phosphorylation was blocked by KN93, a CaMK-II inhibitor. Thus, as one of the consequences of CaMK-II activation, vimentin phosphorylation and rearrangement may support virus replication by playing a structural role for the formation of the replication factories. Collectively, this study identified the replication centers of EV71 in human astrocyte cells. This may help us understand the replication mechanism and pathogenesis of EV71 in human.

  3. Analysis of Neuroimaging features of Enterovirus 71 Related Hand-Foot-Mouth Disease in Acute Stage%EV71型手足口病中枢神经系统并发症急性期影像表现分析

    Institute of Scientific and Technical Information of China (English)

    曾洪武; 黄文献; 林飞飞; 谢娜; 陆普选; 干芸根

    2013-01-01

    目的 分析EV71型手足口病中枢神经系统(CNS)并发症急性期MR表现,探讨其影像学特点及诊断价值.资料与方法 回顾分析经实验室检测确诊为EV71型手足口病,临床诊断其伴CNS并发症的62例患儿的临床资料和影像资料,所有患儿均行头颅和/或脊髓MRI平扫及增强.结果 11例临床诊断脑膜炎者MRI均阴性;10例临床诊断为脑炎者仅1例MRI阳性,主要表现为右顶叶皮质下长T1长T2信号,伴轻度强化.41例脑干脑炎有30例MRI阳性,主要为脑桥延髓交界处长T1长T2信号;11例轻-中度强化,其中5例平扫阴性.17例脊髓炎者11例MRI阳性,9例为脊髓中央灰质长T1长T2信号、未见明显强化,(颈、胸和腰分别为4、3、2例),另2例表现为颈髓横贯性脊髓炎,均同时合并脑干.结论 EV71型手足口病CNS并发症MRI检查阳性主要是脑干脑炎,表现为稍长T1和稍长T2信号,增强MRI可发现平扫为阴性病灶,脑干脑炎可同时累及多个部位,合并颈髓横贯性脊髓炎是病情危重的征象.%Purpose To analyze the neuroimaging features of Enterovius 71 (EV71) related Hand-Foot-Mouth Disease (HFMD) in acute stage,and explore the neuroimage features and diagnostic value.Material and method Clinical and neuroimaging data of 62 cases with lab confirmed EV71 related HFMD in acute stage in 2010 were retrospectively analyzed.All patients underwent crania and/or spine pre and post-contrast MRI.Result 11 cases with aseptic meningitis had normal MRI,only one of the 10 cases with encephalitis had positive MRI result,demonstrating prolonged T1 and T2 signals in right parietal lobe with mild enhancement.30 of the 41 cases with brainstem encephalitis had positive MRI findings,the main lesion located at the junction region between pons and medullar oblongata,presenting as prolonged T1 and T2 signal,11 cases had mild to moderate enhancement,5 of this 11 cases presenting as normal in plain MRI scan.11 of 17clinical myelitis

  4. Recombination in the Evolution of Enterovirus C Species Sub-Group that Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

    OpenAIRE

    Teemu Smura; Soile Blomqvist; Tytti Vuorinen; Olga Ivanova; Elena Samoilovich; Haider Al-Hello; Carita Savolainen-Kopra; Tapani Hovi; Merja Roivainen

    2014-01-01

    Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus). However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C) species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A-C). In this study, the recombination pattern of EV-C species sub-group B that contains ty...

  5. Analysis on genomic characteristics of enterovirus 71 types of VP1 gene in Henan of 2010%河南省2010年肠道病毒71型VP1基因特征分析

    Institute of Scientific and Technical Information of China (English)

    卫海燕; 黄学勇; 许玉玲; 马宏; 陈豪敏; 许汴利

    2012-01-01

    OBJECTIVE To reveal the genomic characteristics of enterovirus 71 strains of VP1 gene from Hand-Foot-Mouth Disease, and analyze their molecular epidemiology. METHODS A total of 840 clinical specimens were collected and isolated, and 34 enterovirus among 71 types of VP1 gene were analyzed by bioinformatics software. RESULTS The VP1 of 34 isolated specimens was gained by sequencing. The nucleotide similarities of VP1 gene were at the range of 96.3% to 100%. Phylogenetic analysis based on VP1 regions revealed that the Henan enterovirus 71 in 2010 belonged to C4a in subgenotype C4, and no difference was found between the severe and mild illness. Cluster C4a enterovirus 71 was also found in henan and other seven provinces during 2003-2009. CONCLUSION 71 isolated strains of enterovirus in Henan of 2008 belong to C4a in the C4 subgenotype, which is in line with the predominant virus circulating in mainland China since 2004.%目的 对河南省2010年手足口病监测标本进行病原分离及VP1基因测序,了解分离病毒的基因特征及分子流行病学特点.方法 将2010年收集的手足口病患者粪便标本和肛拭子标本840份进行病毒分离鉴定并对34株病毒分离株测定肠道病毒71型VP1全序,利用生物信息学软件对序列分析,构建序列系统进化树.结果 测序获得34株来自河南省11个地市的VP1全长序列,分离株间的VP1区核苷酸相似性为96.3%~100%,系统进化分析显示属于C4基因型的C4a亚群,所有分离株均处于同一进化分支,轻重症间无明显差别.在2003~2009年的河南省和其他7省亦发现有C4a亚群存在.结论 2010年河南EV71分离株为C4基因型的C4a亚群,河南省2008年以来的分离株与2004年以来的中国大陆优势株流行趋势完全一致.

  6. DETECTION OF HUMAN ENTEROVIRUS AND ADENOVIRUS IN SHELLFISH COLLECTED IN MOROCCO MEDITERRANEAN COAST

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    Laila Benabbes

    2013-10-01

    Full Text Available The aim of this study was the screening for the presence of enteric human virus in shellfish (clam and cockle collected from two production area in Moroccan Mediterranean coast. Between October 2006 and April 2008, forty four samples were collected and tested for viral contamination using cell culture (HEp-2 and Vero cells and integrated cell culture PCR. Overall, 88.6 % of all analysed samples were contaminated by at least one of the studied viruses, Adenovirus was detected in 52.3 % of the samples and Enterovirus in 36.3%. The presence of viruses in shellfish production area can represent a potential health risk by causing gastroenteritis. The procedure used in this study may be a tool for monitoring shellfish viral contamination in Morocco.

  7. Detection and genotyping of enteroviruses in cerebrospinal fluid in patients in Victoria, Australia, 2007-2013.

    Science.gov (United States)

    Papadakis, Georgina; Chibo, Doris; Druce, Julian; Catton, Michael; Birch, Chris

    2014-09-01

    Genotyping by VP1 fragment polymerase chain reaction (PCR) and nucleic acid sequencing to detect enterovirus (EV) genotypes was performed directly on 729 EV PCR positive cerebrospinal fluid (CSF) samples collected between 2007 and 2012 from Victorian hospital inpatients. The overall genotype identification rate from CSF-positive material was 43%. The four most common genotypes identified were Echovirus 6 (24%), Echovirus 30 (17%), Echovirus 25 (10%), and Coxsackievirus A9 (10%), together comprising 61% of all EVs typed. The seasonal distribution of all EVs identified followed the recognized pattern of mainly summer epidemics. Three of the four predominant genotypes were present in each of the 6 years in which the study was conducted, with 20 other EV genotypes also detected, often in only a single year. Genotyping of EVs directly in CSF is faster, simpler and more sensitive than traditional virus neutralization assays performed on EV positive samples. © 2014 Wiley Periodicals, Inc.

  8. Evaluation of the enterovirus laboratory surveillance system in Denmark, 2010 to 2013

    DEFF Research Database (Denmark)

    Condell, Orla; Midgley, Sofie; Christiansen, Claus Bohn;

    2016-01-01

    -transmission in a timely manner. We evaluate the national EV laboratory surveillance, to generate recommendations for system strengthening. The system was analysed for completeness of viral typing analysis and clinical information and timeliness of specimen collection, laboratory results and reporting of clinical......The primary aim of the Danish enterovirus (EV) surveillance system is to document absence of poliovirus infection. The conflict in Syria has left many children unvaccinated and movement from areas with polio cases to Europe calls for increased awareness to detect and respond to virus......-confirmed cases, clinical information was available for 63.1% (903/1,430). Primary diagnostic results were available after a median of 1.4 days, typing results after 17 days, detailed clinical information after 33 days. The large number of samples typed demonstrated continued monitoring of EV...

  9. Monitoring antigenic variations of enterovirus 71: implications for virus surveillance and vaccine development.

    Directory of Open Access Journals (Sweden)

    Min-Yuan Chia

    2014-07-01

    Full Text Available Enterovirus 71 (EV71 causes life-threatening epidemics in Asia and can be phylogenetically classified into three major genogroups (A ∼ C including 11 genotypes (A, B1 ∼ B5, and C1 ∼ C5. Recently, EV71 epidemics occurred cyclically in Taiwan with different genotypes. In recent years, human studies using post-infection sera obtained from children have detected antigenic variations among different EV71 strains. Therefore, surveillance of enterovirus 71 should include phylogenetic and antigenic analysis. Due to limitation of sera available from children with EV71 primary infection, suitable animal models should be developed to generate a panel of antisera for monitoring EV71 antigenic variations. Twelve reference strains representing the 11 EV71 genotypes were grown in rhabdomyosarcoma cells. Infectious EV71 particles were purified and collected to immunize rabbits. The rabbit antisera were then employed to measure neutralizing antibody titers against the 12 reference strains and 5 recent strains. Rabbits immunized with genogroup B and C viruses consistently have a lower neutralizing antibody titers against genogroup A (≧ 8-fold difference and antigenic variations between genogroup B and C viruses can be detected but did not have a clear pattern, which are consistent with previous human studies. Comparison between human and rabbit neutralizing antibody profiles, the results showed that ≧ 8-fold difference in rabbit cross-reactive antibody ratios could be used to screen EV71 isolates for identifying potential antigenic variants. In conclusion, a rabbit model was developed to monitor antigenic variations of EV71, which are critical to select vaccine strains and predict epidemics.

  10. Inferring nonneutral evolution from contrasting patterns of polymorphisms and divergences in different protein coding regions of enterovirus 71 circulating in Taiwan during 1998-2003

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    Chen Guang-Wu

    2010-09-01

    Full Text Available Abstract Background Enterovirus (EV 71 is one of the common causative agents for hand, foot, and, mouth disease (HFMD. In recent years, the virus caused several outbreaks with high numbers of deaths and severe neurological complications. Despite the importance of these epidemics, several aspects of the evolutionary and epidemiological dynamics, including viral nucleotide variations within and between different outbreaks, rates of change in immune-related structural regions vs. non-structural regions, and forces driving the evolution of EV71, are still not clear. Results We sequenced four genomic segments, i.e., the 5' untranslated region (UTR, VP1, 2A, and 3C, of 395 EV71 viral strains collected from 1998 to 2003 in Taiwan. The phylogenies derived from different genomic segments revealed different relationships, indicating frequent sequence recombinations as previously noted. In addition to simple recombinations, exchanges of the P1 domain between different species/genotypes of human enterovirus species (HEV-A were repeatedly observed. Contrasting patterns of polymorphisms and divergences were found between structural (VP1 and non-structural segments (2A and 3C, i.e., the former was less polymorphic within an outbreak but more divergent between different HEV-A species than the latter two. Our computer simulation demonstrated a significant excess of amino acid replacements in the VP1 region implying its possible role in adaptive evolution. Between different epidemic seasons, we observed high viral diversity in the epidemic peaks followed by severe reductions in diversity. Viruses sampled in successive epidemic seasons were not sister to each other, indicating that the annual outbreaks of EV71 were due to genetically distinct lineages. Conclusions Based on observations of accelerated amino acid changes and frequent exchanges of the P1 domain, we propose that positive selection and subsequent frequent domain shuffling are two important mechanisms

  11. Progress in quality control in developing enterovirus 71 vaccine%肠道病毒71型疫苗质量控制研究进展

    Institute of Scientific and Technical Information of China (English)

    王一平; 姚昕(综述); 毛群颖; 梁争论(审校)

    2015-01-01

    Hand foot and mouth disease ( HFMD) has become the serious public health problem in Asia-Pacific region, and enterovirus 71 (EV71) was the major causative agent for HFMD.The development of EV71 vaccine was the effective method for controlling HFMD.The inactivated EV71 whole-virus vaccines from five manufacturers entered clinical trials in the world.The vaccines from three manufacturers in China have been completed the phase III clinical trials.Clinical results indicated that these vaccines have a high efficacy, satisfactory safety, and sustained immunogenicity.However, it is a gap to establish the quality control of antigen content and standard in development of a vaccine.The detection of antigen content is the crucial item for optimization in production process, evaluation of immunogenicity and dose selection.This article summarized the progress on quality control of EV71 antigen.%手足口病( Hand foot and mouth disease,HFMD)已成为西太平洋区严重的公共卫生问题之一,肠道病毒71型(Enterovirus 71,EV71)是引起HFMD的主要病原体,研发疫苗是控制HFMD流行的有效手段。目前世界范围已有5个EV71全病毒灭活疫苗进入临床试验,其中中国研制的3种EV71疫苗已分别完成III期临床试验,结果表明3种疫苗都具有良好的安全性和保护效果。在EV71疫苗研发中,抗原质控的方法和标准是研发的瓶颈,其中抗原活性测定是工序工艺优化、免疫原性评价和剂量确定的关键指标。综述了EV71疫苗抗原质控的研究进展。

  12. [An experience in applying Watson's theory in caring for an enterovirus-infected child and his primary caregiver].

    Science.gov (United States)

    Wen, Shu-Hui; Wu, Li-Min

    2004-06-01

    Enterovirus is commonly seen in children. Its morbidity and mortality rate is about 18% (Department of Health, the Executive Yuan, 2003). This paper documents the use of Watson's theory in the care of a child aged two years and seven months and his primary caregiver. During the nursing process, the application of care and concern for the child and primary caregiver provided confidence, comfort, and relief of fear and anxiety caused by hospitalization, enabling the patient, during his time in hospital, to make physical and psychological progress. The caregiver was also able to gain an understanding of how to care for a child with enterovirus, which diminished some of the pressure caused by his admission to hospital and placed him and his family at the center of the nursing care.

  13. Hand, foot, and mouth disease caused by coxsackievirus A6, Thailand, 2012.

    Science.gov (United States)

    Puenpa, Jiratchaya; Chieochansin, Thaweesak; Linsuwanon, Piyada; Korkong, Sumeth; Thongkomplew, Siwanat; Vichaiwattana, Preyaporn; Theamboonlers, Apiradee; Poovorawan, Yong

    2013-04-01

    In Thailand, hand, foot, and mouth disease (HFMD) is usually caused by enterovirus 71 or coxsackievirus A16. To determine the cause of a large outbreak of HFMD in Thailand during June-August 2012, we examined patient specimens. Coxsackievirus A6 was the causative agent. To improve prevention and control, causes of HFMD should be monitored.

  14. Isolation of enteroviruses from water, suspended solids, and sediments from Galveston Bay: survival of poliovirus and rotavirus adsorbed to sediments.

    OpenAIRE

    Rao, V. C.; Seidel, K M; Goyal, S M; Metcalf, T. G.; Melnick, J L

    1984-01-01

    The distribution and quantitation of enteroviruses among water, suspended solids, and compact sediments in a polluted estuary are described. Samples were collected sequentially from water, suspended solids, fluffy sediments (uppermost layer of bottom sediments), and compact sediment. A total of 103 samples were examined of which 27 (26%) were positive for virus. Polioviruses were recovered most often, followed by coxsackie B viruses and echoviruses 7 and 29. Virus was found most often attache...

  15. [Detection of enterovirus RNA in cerebrospinal fluid from patients with aseptic meningitis and encephalitis and its clinical significance].

    Science.gov (United States)

    Li, A; Chen, Z; Liu, Q

    2001-12-01

    To study the pathogenicity of enterovirus (EV) infection in central nervous system and the method for its detection. Using reverse transcription polymerase chain reaction (RT-PCR) and viral culture techniques to detect EV from 46 cerebrospinal fluid (CSF) samples of aseptic meningitis and encephalitis patients. The sensitivity and specificity of RT-PCR for EV RNA detection was affirmed by specific RNA identification of 40 strains of prototype enterovirus. By the virus culture method, 14 out of the 46 CSF sample were tested to beEV positive (26.1%) including 6 Echovirus type 2 (ECV2), 2 Coxackie virus type B2 (CVB2), 2CVB6, 1 ECV3 and 1 ECV11. By RT-PCR method, 31 of 46 CSF sample were tested EV RNA positive (67.4%) through amplified product agarose electrophoresis and northern blot hybridizition. The positive CSF included 14 samples that had been tested positive by virus culture and 17 samples that accounted for 53.9% of the 32 CSF samples which were negetive by virus culture. The sensitivity of RT-PCR was statistically higher than that of the virus culture method, Chi(2) =12.57, P <0.01. EV is known as important etiological agents of aseptic meningitis and encephalitis. RT-PCR is sensitivity, specificity and rapidity, it may be popularized as an effective method to the detection of enterovirus.

  16. Routine Pediatric Enterovirus 71 Vaccination in China: a Cost-Effectiveness Analysis.

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    Joseph T Wu

    2016-03-01

    Full Text Available China accounted for 87% (9.8 million/11.3 million of all hand, foot, and mouth disease (HFMD cases reported to WHO during 2010-2014. Enterovirus 71 (EV71 is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6-71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China.We characterized the economic and health burden of EV71-associated HFMD (EV71-HFMD in China using (i the national surveillance database, (ii virological surveillance records from all provinces, and (iii a caregiver survey on the household costs and health utility loss for 1,787 laboratory-confirmed pediatric cases. Using a static model parameterized with these data, we estimated the effective vaccine cost (EVC, defined as cost/efficacy or simply the cost of a 100% efficacious vaccine below which routine pediatric vaccination would be considered cost-effective. We performed the base-case analysis from the societal perspective with a willingness-to-pay threshold of one times the gross domestic product per capita (GDPpc and an annual discount rate of 3%. We performed uncertainty analysis by (i accounting for the uncertainty in the risk of EV71-HFMD due to missing laboratory data in the national database, (ii excluding productivity loss of parents and caregivers, (iii increasing the willingness-to-pay threshold to three times GDPpc, (iv increasing the discount rate to 6%, and (v accounting for the proportion of EV71-HFMD cases not registered by national surveillance. In each of these scenarios, we performed probabilistic sensitivity analysis to account for parametric uncertainty in our estimates of the risk of EV71-HFMD and the expected costs and health utility loss due to EV71-HFMD. Routine pediatric EV71 vaccination would be cost-saving if the all-inclusive EVC is below US$10.6 (95% CI US$9.7-US$11.5 and would remain cost-effective if EVC is below US$17.9 (95% CI US$16.9-US$18.8 in

  17. Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants

    Institute of Scientific and Technical Information of China (English)

    MAO Qun-ying; LU Feng-min; ZHUANG Hui; LIAO Xue-yan; YU Xiang; LI Nan; ZHU Feng-cai; ZENG Ying; LIANG Zheng-lun; LI Feng-xiang; WANG Jun-zhi

    2010-01-01

    Background Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. The aims of our study were: to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course.Methods Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively.Results Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P <0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months.Conclusions The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.

  18. Research progress of 2A protein of enterovirus 71%肠道病毒71型2A蛋白的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘永娟; 张凤凤; 涂会林; 何小华; 刘万红

    2014-01-01

    肠道病毒71 (enterovirus 71,EV71)是手足口病(hand,foot and mouth disease,HFMD)主要致病原之一.手足口病临床上常表现为发热,手掌、脚掌及口腔黏膜皮疹或疱疹.然而,EV71感染导致的手足口病易伴随神经系统并发症,甚至死亡.EV71非结构蛋白2A作为蛋白酶和转录激活因子,在EV71生命周期中发挥重要作用.本文对2A的结构与功能研究进展进行综述,揭示2A的双重功能如何促进病毒复制和调控靶细胞,为进一步研究靶向2A的抗病毒疫苗和药物提供理论基础.

  19. 肠道病毒71型的分子流行病学现况%Molecular Epidemiological Research on Enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    檀晓娟; 许文波

    2008-01-01

    目的 肠道病毒71(Enterovirus 71,EV71)是导致婴幼儿感染的重要病原之一,可引起多种疾病,具有较广的疾病谱.EV71可引起大规模的手足口病(Hand,Foot,and Mouth Disease,HFMD)爆发,也可引起脑干脑炎等神经系统感染,导致死亡.现对EV71分子流行病学研究方法和研究进展进行综述,总结和分析了EV71各种基因型/亚型毒株的进化史及进化地位,对国际上EV71各种基因型/亚型的流行现况进行了概括总结.

  20. 肠道病毒71型致病机制研究进展%Advances in pathogenic mechanisms of enterovirus 71

    Institute of Scientific and Technical Information of China (English)

    刘雪

    2013-01-01

    肠道病毒71型(EV71)是引起手足口病的主要病原体之一,已经引起世界各地的大范围流行,可引起严重的并发症并导致患儿死亡.其引起严重并发症的致病机制尚不清楚,与许多因素有关包括细胞趋向、细胞凋亡和宿主免疫反应.该文主要介绍决定EV71细胞趋向的因素,引起细胞凋亡的相关机制及宿主免疫反应在EV71致病机制中的作用.%Enterovirus 71 (EV71) is one of the major pathogens that cause hand foot and mouth disease.Epidemics and pandemics have been periodically reported worldwide.EV71 also can cause serous complications and lead death in children.The mechanisms of EV71 cause serious complications has remained unclear,may relate to many factors,including cell tropism,cell death and host immune responses.This article reviews the recent advances in the identification of factors determining EV71 cell tropism,the associated mechanisms of viral infection-induced cell death and the interplay between EV71 and immunity.

  1. Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Ku

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear. METHODS/FINDINGS: In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs. Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment. CONCLUSIONS: Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.

  2. Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.

    Science.gov (United States)

    Chen, M-F; Weng, K-F; Huang, S-Y; Liu, Y-C; Tseng, S-N; Ojcius, D M; Shih, S-R

    2017-01-01

    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 with production of monocyte chemoattractant protein-1 (MCP-1). The intratracheal injection of a recombinant mouse MCP-1 protein abrogated the antiviral effects elicited by pretreatment with E. faecalis. CC chemokine receptor 2 (CCR2) is a receptor for MCP-1, and the intraperitoneal administration of a CCR2 antagonist effectively inhibited viral pathogenicity. The reduced pathogenicity was also observed in CCR2-deficient mice. Finally, E. faecalis significantly attenuated neuropathogenicity induced by another RNA virus, enterovirus 71. This study demonstrates that killed probiotics can reduce viral disease severity and identify that the MCP-1 pathway might act as a key mediator in the improved antiviral immune response. Our findings suggest that MCP-1 and its related signaling pathway can serve as critical therapeutic targets for development of new antiviral strategies.

  3. 肠道病毒71型的生物学特征与实验室诊断%Biological Features and Laboratory Diagnosis of Enterovirus Type 71

    Institute of Scientific and Technical Information of China (English)

    杨峻; 郑文岭; 马文丽

    2008-01-01

    肠道病毒71型(enterovirus type 71,EV71)感染可以导致手足口病(hand foot and mouth disease,HFMD)、无菌性脑膜炎(asepicmeningitis)、脑炎(encephalitis)和脊髓灰质炎样的麻痹性疾病(poliomyeli-tis-like paralysis)等多种神经系统疾病.早期、快速、准确的诊断对EV71的预防和隔离至关重要.随着分子生物学技术的发展,基因芯片技术因具有高通量性、快速、准确性强等特点,成为新兴的病毒检测技术.

  4. 对"肠道病毒71型感染首发肺水肿与肺出血三例报告"一文的看法%Expert's Comment on the article entitled Three cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation

    Institute of Scientific and Technical Information of China (English)

    陈贤楠

    2008-01-01

    @@ Cases with severe enterovirus 71 ( EV71 ) infection have been reported outside the mainland of China since the 1990s[1]. The epidemics of the infection occurred and lasted for a long time in some places in China in the spring of 2007 and deaths caused by the infection had been reported. The epidemics of EV71 infection occurred again this year in Southern regions of China. Three cases reported in this issue had severe EV71 infection without skin eruption, and had confirmed evidence for pathogenesis. The report of these cases is helpful to pediatricians to recognize the manifestations of this disease.

  5. Children’s Caregivers and Public Playgrounds: Potential Reservoirs of Infection of Hand-foot-and-mouth Disease

    Science.gov (United States)

    Li, Pengyuan; Li, Tao; Gu, Qiuyun; Chen, Xiaomin; Li, Jiahui; Chen, Xiashi; Chen, Yan; Zhang, Danwei; Gao, Rong; He, Zhenjian; Zhu, Xun; Zhang, Wangjian; Hao, Yuantao; Zhang, Dingmei

    2016-11-01

    Hand-foot-and-mouth disease (HFMD) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in China. This study aimed to exploring the effects on HFMD transmission of children’s caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. Total children’s 257 samples (98 children’s caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71, coxsackie virus A6 and A16 by real-time fluorescence quantitative polymerase chain reaction (qPCR). 5.84% (15/257, 95% confidence interval [CI]: 2.98%, 8.70%) of total samples had positive results of enterovirus. The enterovirus positive rates of children’s caregiver samples and environmental samples were respectively 7.14% (7/98, 95% CI: 2.04%, 12.24%), and 5.03% (8/159, 95% CI: 1.63%, 8.43%); 7.61% (7/92, 95% CI: 2.21%, 13.01%) of wiping samples from playgrounds and 1.49% (1/67, 95% CI: 0, 7.00%) of air samples in indoor market places had positive result of enterovirus. High positive rates of enterovirus in children’s caregivers and from playgrounds indicated that they would be potential reservoirs of HFMD infection, as children might be infected via contacting with asymptomatic-infected individuals or exposure of contaminated surface of public facilities.

  6. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    Science.gov (United States)

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  7. Histopathological features and distribution of EV71 antigens and SCARB2 in human fatal cases and a mouse model of enterovirus 71 infection.

    Science.gov (United States)

    Yu, Pin; Gao, Zifen; Zong, Yuanyuan; Bao, Linlin; Xu, Lili; Deng, Wei; Li, Fengdi; Lv, Qi; Gao, Zhancheng; Xu, Yanfeng; Yao, Yanfeng; Qin, Chuan

    2014-08-30

    Enterovirus 71 (EV71) is a neurotropic pathogen that causes hand, foot, and mouth disease. While infection is usually self-limiting, a minority of patients infected with EV71 develop severe neurological complications. In humans, EV71 has been reported to utilize the scavenger receptor class B, member 2 (SCARB2) as a receptor for infectious cellular entry. In this study, we define the pathological features of EV71-associated disease as well as the distribution of EV71 antigen and SCARB2 in human fatal cases and a mouse model. Histopathologically, human fatal cases showed severe central nervous system (CNS) changes, mainly in the brainstems, spinal cords, and thalamus. These patient further exhibited pulmonary edema and necrotic enteritis. Immunohistochemical analysis of human fatal cases demonstrated that EV71 antigen and SCARB2 were observed mainly in neurons, microglia cells and inflammatory cells in the CNS, and epithelial cells in the intestines. However, skeletal muscle tissue was negative for EV71 antigen. In a mouse model of EV71 infection, we observed massive necrotic myositis, different degrees of viral diseases in CNS, and extensive interstitial pneumonia. In mice, EV71 exhibits strong myotropism compared to the neurotropism seen in humans. EV71 antigen was detected in the spinal cord and brainstem of mice. However, there was no clear correlation between mouse SCARB2 and EV71 antigen distribution in the mouse model, consistent with previous results that SCARB2 functions as a receptor for EV71 in humans but not mice. The EV71-induced lesions seen in the mouse model resembled the pathological changes seen in human samples. These results increase our understanding of EV71 pathogenesis and will inform further work developing a mouse model for EV71 infection.

  8. Complete coding regions of the prototypes enterovirus B93 and C95: phylogenetic analyses of the P1 and P3 regions of EV-B and EV-C strains.

    Science.gov (United States)

    Junttila, N; Lévêque, N; Magnius, L O; Kabue, J P; Muyembe-Tamfum, J J; Maslin, J; Lina, B; Norder, H

    2015-03-01

    Complete coding regions were sequenced for two new enterovirus genomes: EV-B93 previously identified by VP1 sequencing, derived from a child with acute flaccid paralysis in the Democratic Republic of Congo; and EV-C95 from a French soldier with acute gastroenteritis in Djibouti. The EV-B93 P1 had more than 30% nucleotide divergence from other EV-B types, with highest similarity to E-15 and EV-B80. The P1 nucleotide sequence of EV-C95 was most similar, 71%, to CV-A21. Complete coding regions for the new enteroviruses were compared with those of 135 EV-B and 176 EV-C strains representing all types available in GenBank. When strains from the same outbreak or strains isolated during the same year in the same geographical region were excluded, 27 of the 58 EV-B, and 16 of the 23 EV-C types were represented by more than one sequence. However, for EV-B the P3 sequences formed three clades mainly according to origin or time of isolation, irrespective of type, while for EV-C the P3 sequences segregated mainly according to disease manifestation, with most strains causing paralysis, including polioviruses, forming one clade, and strains causing respiratory illness forming another. There was no intermixing of types between these two clades, apart from two EV-C96 strains. The EV-B P3 sequences had lower inter-clade and higher intra-clade variability as compared to the EV-C sequences, which may explain why inter-clade recombinations are more frequent in EV-B. Further analysis of more isolates may shed light on the role of recombinations in the evolution of EV-B in geographical context.

  9. Three cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation%肠道病毒71型感染首发肺水肿与肺出血三例报告

    Institute of Scientific and Technical Information of China (English)

    何时军; 王霞; 郑晓群; 王传夏; 黄爱蓉; 金益梅; 杨好妹; 周爱华

    2008-01-01

    Objective To investigate the clinical features of the enterovirus 71 ( EV71 ) infection complicated with pulmonary edema or pulmonary hemorrhage as a fulminant and often fatal illness.Methods The medical records of three cases with EV71 infection were retrospectively reviewed for clinical manifestations, laboratory data, medications, and outcome.Results All the cases were infants and died of the infection. These infants had no skin or mucosal lesions, however, they had sudden onset of cyanosis and tachypnea 1 to 2 days after the onset of the febrile disease with vomiting. All these 3 cases were misdiagnosed and were treated for shock on admission. Pulmonary hemorrhage was not considered in any of the cases on admission. All the cases received tracheal intubation when foamy secretions were discharged from the mouth and nose of the patients and notable cyanosis occurred. After intubation, pink foamy fluid flew out from the endotracheal tube in all the 3 cases. The patients had hyperglycemia and limb weakness, two had tachycardia, and hypertension was found in one case. Chest X-ray showed bilateral or unilateral widespread air space opacity, but the cardiac size and shape were normal. All the patients had leukocytosis. Enterovirus 71 infection was confirmed by detection of specific nucleic acid sequences of the virus from throat swab and tracheal secretions samples and in one case in cerebrospinal fluid.Conclusions Pulmonary edema or pulmonary hemorrhage occurred in the 3 cases with EV71 infection. The initial presentation was nonspecific with fever and vomiting, and sudden appearance of cyanosis, tachypnea, tachycardia, hypertension or hypotension, limb weakness, which may suggest pulmonary edema or hemorrhage. Excessive fluid resuscitation may deteriorate the illness, on the contrary, fluid restriction and inotropic agents, and early intubation with positive pressure mechanical ventilation may be the proper treatment.

  10. Presence of certain enteroviruses (Coxsackie) in sewage effluents and in river waters of Roumania.

    Science.gov (United States)

    Nestor, I; Costin, L

    1976-01-01

    The paper presents the results of research studies conducted during a 10-year period (1962-1971) with the view to detect certain enteroviruses (Coxsackie) from sewage, river and drinking water samples, and from the filter sand of drinking water-works supplied with river water. The method consisted first in preconcentrating the samples collected on immersed gauze pads, secondly in the concentration of the virus samples by the following methods-used either separately or in parallel: the Amberlite method, the yeast cell and the aluminium bydroxide concentration method. The isolation of A and B Coxackie viruses averaged 29.12% in the sewage samples and 14.66% in the river water samples. Lower values were found both in aqueduct water and in the filter sand (2 positive samples out of 65 and 3 positive samples out of 39, respectively). A seasonal distribution of the viral incidence was evidenced in the sewage samples with lower value in the river water, while the frequency decreased with the distance from the pollution source. For the lightly contaminated water (river and aqueduct waters) the yeast cell concentration method gave the best results, this method being also the single reliable method for Coxsackie virus isolation from the filter sand samples.

  11. In vitro screening of traditionally used medicinal plants in China against Enteroviruses

    Institute of Scientific and Technical Information of China (English)

    Jin-Peng Guo; Ji Pang; Xin-Wei Wang; Zhi-Qiang Shen; Min Jin; Jun-Wen Li

    2006-01-01

    AIM: To search for new antiviral agents from traditional Chinese medicine, specifically anti-enterovirosuses agents.METHODS: The aqueous extracts (AE) of more than 100 traditionally used medicinal plants in China were evaluated for their in vitro anti-Coxsackie virus B3 activities with a NTT-based colorimetric assay.RESULTS: The test for AE of 16 plants exhibited antiCoxsackie virus B3 activities at different magnitudes of potency. They can inhibit three steps (inactivation,adsorption and replication) during the infection. Among the 16 plants, Sargentodoxa cuneata (Oliv.) Rehd. et Wils., Sophora tonkinensis Gapnep., Paeonia veitchii Lynch, Spatholobus suberectus Dunn. and Cyrtomium fortunei J. sm. also have activity against other enterovirus, including Coxsackie virus B5, Polio virus I, Echo virus 9 and Echo virus 29. Cell cytotoxic assay demonstrated that all tested AE had CC 50 values higher than their EC50 values.CONCLUSION: The sixteen traditionally used medicinal plants in China possessed antiviral activity, and some of them merit further investigations.

  12. Respiratory Presentation of Pediatric Patients in the 2014 Enterovirus D68 Outbreak

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    Georgina Martin

    2016-01-01

    Full Text Available Background. In the fall of 2014, a North American outbreak of enterovirus D68 resulted in a significant number of pediatric hospital admissions for respiratory illness throughout North America. This study characterized the clinical presentation and risk factors for a severe clinical course in children admitted to British Columbia Children’s Hospital during the 2014 outbreak. Methods. Retrospective chart review of patients with confirmed EV-D68 infection admitted to BCCH with respiratory symptoms in the fall of 2014. Past medical history, clinical presentation, management, and course in hospital was collected and analyzed using descriptive statistics. Comparison was made between those that did and did not require ICU admission to identify risk factors. Results. Thirty-four patients were included (median age 7.5 years. Fifty-three percent of children had a prior history of wheeze, 32% had other preexisting medical comorbidities, and 15% were previously healthy. Ten children (29% were admitted to the pediatric intensive care unit. The presence of complex medical conditions (excluding wheezing (P=0.03 and copathogens was associated with PICU admission (P=0.02. Conclusions. EV-D68 infection resulted in severe, prolonged presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of wheeze and preexisting medical comorbidities appear to be most severely affected, but the virus can also cause wheezing in previously well children.

  13. Enterovirus type 71 2A protease functions as a transcriptional activator in yeast

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    Lai Meng-Jiun

    2010-08-01

    Full Text Available Abstract Enterovirus type 71 (EV71 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis.

  14. A Novel Pharmacophore Model Derived from a Class of Capsid Protein Enterovirus 71 Inhibitors

    Institute of Scientific and Technical Information of China (English)

    DUAN Hong-Xia; YANG Xin-Ling; WANG Dao-Quan; NING Jun; MEI Xiang-Dong; ZHANG Jian

    2012-01-01

    Capsid protein enterovirus 71 (EV71) is one of the major viruses that cause the severe encephalitis and thus result in a high mortality in children less than 5 years of age.In an effort to discover new potent inhibitors against EV71,a novel three-dimensional pharmacophore model was developed on 24 inhibitors with different molecular structures and bioactivities.The best hypothesis (Hypo1) has a high predictive power and consists of four features,namely,one hydrophobic point (HY) and three hydrogen-bond acceptors (HA).Two key features of the best Hypo1,HY1 and HA3 match well with an important narrow hydrophobic canyon and with the surface of LYS274 in the target EV71 active site,respectively.The more versatile feature,HA1,is firstly found to be very influential on these compounds’ bioactivities,which may interact with the other side of the active site in the EV71 receptor.The application of the model is successful in predicting the activities of 30 known EV71 inhibitors with a correlation coefficient of 0.831.Furthermore,Hypo1 demonstrates a superior screening capability for retrieving inhibitors from the database with a high enrichment factor of 70.This study provides some important clues in search for more potent inhibitors against EV71 infection.

  15. Safe and Objective Assay of Enterovirus 71 Neutralizing Antibodies via Pseudovirus

    Institute of Scientific and Technical Information of China (English)

    JIN Jun; XU Lin; GUO Shi-jie; SUN Shi-yang; ZHANG Shu; ZHU Chang-lin; KONG Wei; JIANG Chun-lai

    2012-01-01

    Current serum neutralization assays based on the inhibition of the eytopathic effect(Nt-CPE) need to manipulate live viruses,which are time-consuming,labor-intensive,and have the potential exposure to infectious agents,so a safe and objective assay via pseudovirus for the fast and efficient detection of enterovirus 71(EV71 ) neutralizing antibodies was developed.First,we generated EV71 pseudovirus containing firefly luciferase gene in place of the capsid gene P1 in EV71 genome.Vero cells infected with 200 CCID50(50% cell culture infective dose) of EV71 pseudovirus for 24 h were found to have the best performance.Seval sera were measured by EV71 pseudoparticle neutralization assay(Nt-PPN) and the conventional serological method Nt-CPE.Neutralizing antibody titers measured by Nt-PPN and those obtained by Nt-CPE demonstrate a high correlation between the two methods.Overall,the PPN assay represents a valid alternative to conventional serological methods for the evaluation of EV71 neutralizing antibodies.This method can be used for detecting neutralizing antibodies of other picornaviruses,such as hepatitis A virus(HAV) and coxsackievirus 16(CVA16),and make it possible to determine whether there is cross-reactivity between EV71 and CVA16.

  16. Progress on the research and development of human enterovirus 71 (EV71) vaccines.

    Science.gov (United States)

    Liang, Zhenglun; Mao, Qunying; Gao, Fan; Wang, Junzhi

    2013-03-01

    Enterovirus 71 (EV71) infections, which can cause severe complications, have become one of the serious public health issues in the Western Pacific region and China. To date, a number of pharmaceutical companies and institutes have initiated the research and development of EV71 vaccines as a countermeasure. As is the case with innovative vaccine development, there are several critical bottlenecks in EV71 vaccine development that must be overcome before the clinical trials, including the selection of vaccine strain, standardization of the procedure for quantifying neutralizing antibody (NTAb) and antigen, establishment and application of a reference standard and biological standards, development of animal models for the evaluation of protective efficacy, and identification of the target patient population. To tackle these technical obstacles, researchers in Mainland of China have conducted a series of studies concerning the screening of vaccine strains and the establishment of criteria, biological standards and detection methods, thereby advancing EV71 vaccine development. This review summarizes recent worldwide progress on the quality control and evaluation of EV71 vaccines.

  17. Development of a Specific Latex Agglutination Test to Detect Antibodies of Enterovirus 71.

    Science.gov (United States)

    Qin, Bo; Zhang, Jianhua; Xie, Wenhao; Liu, Xuehong; He, Tingting; Chen, Jinkun; Dong, Xuejun

    2015-10-01

    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 VP1-LAT showed a sensitivity of 87.0%, specificity of 88.9%, and an agreement ratio of 90.0% in detecting VP1 in 100 serum samples from experimentally infected mice, whereas these values were 86.8, 96.7, and 93.3%, respectively, for 608 clinical human serum samples. The VP1-LAT has advantages over other assays in terms of low cost, rapidity, chemical stability, high sensitivity, repeatability, and specificity. The LAT established in the present study is a rapid and simple test suitable for field monitoring of antibodies against VP1-EV71.

  18. Enterovirus meningitis in Tunisia (Monastir, Mahdia, 2011-2013): identification of virus variants cocirculating in France.

    Science.gov (United States)

    Othman, Ines; Volle, Romain; Elargoubi, Aida; Guediche, Mohamed Neji; Chakroun, Mohamed; Sfar, Mohamed Tahar; Pereira, Bruno; Peigue-Lafeuille, Hélène; Aouni, Mahjoub; Archimbaud, Christine; Bailly, Jean-Luc

    2016-02-01

    Acute enterovirus (EV) meningitis is a frequent cause of hospitalisation, and over 100 EV serotypes may be involved. A total of 215 patients of all ages with meningitis signs were investigated in 2 Tunisian hospitals. Their cerebrospinal fluid (CSF) was analysed retrospectively for EVs with a TaqMan real-time RT-qPCR. The virus strains were typed, and their evolutionary relationships were determined by Bayesian phylogenetic methods. An EV genome was detected in 21/215 patients (9.8%). The CSF viral loads ranged from 3.27 to 5.63 log10 genome copies/mL. The strains were identified in 13/21 patients and assigned to EV-B types. Viruses identified in Tunisian patients were genetically related to variants detected in France. The viral loads were similar in Tunisian and French patients for most EV types. The phylogenetic data and viral loads determined in Tunisian and French patients suggest that close EV variants were involved in aseptic meningitis in the 2 countries over a same period.

  19. The Role of Lipid Rafts in the Early Stage of Enterovirus 71 Infection

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    Yong-Zhe Zhu

    2015-02-01

    Full Text Available Background/Aims: Although it has been widely accepted that Enterovirus 71 (EV71 enters permissive cells via receptor-mediated endocytosis, the details of entry mechanism for EV71 still need more exploration. This study aimed to investigate the role of lipid rafts in the early stage of EV71 Infection. Methods: The effect of cholesterol depletion or addition of exogenous cholesterol was detected by immunofluorescence assays and quantitative real-time PCR. Effects of cholesterol depletion on the association of EV71 with lipid rafts were determined by flow cytometry and co-immunoprecipitation assays. Localization and internalization of EV71 and its receptor were assayed by confocal microscpoy and sucrose gradient analysis. The impact of cholesterol on the activation of phosphoinositide 3'-kinase/Akt signaling pathway during initial virus infection was analyzed by Western-blotting. Results: Disruption of membrane cholesterol by a pharmacological agent resulted in a significant reduction in the infectivity of EV71. The inhibitory effect could be reversed by the addition of exogenous cholesterol. Cholesterol depletion post-infection did not affect EV71 infection. While virus bound equally to cholesterol-depleted cells, EV71 particles failed to be internalized by cholesterol-depleted cells. EV71 capsid protein co-localized with cholera toxin B, a lipid-raft-dependent internalization marker. Conclusion: Lipid rafts play a critical role in virus endocytosis and in the activation of PI3K/Akt signaling pathway in the early stage of EV71 infection.

  20. 人肠道病毒71型疫苗研究进展%Research progress of human enterovirus 71 vaccine

    Institute of Scientific and Technical Information of China (English)

    谢明玉; 彭琪; 陆小梅; 钟柏茂

    2016-01-01

    Human enterovirus 71 (HEV71) is a major causative agent of hand,foot and mouth disease.Children infection with HEV71 can lead to series of neurological complications including aseptic meningitis,cerebral ataxia and even fatal outcomes.During recent decades,epidemic of hand,foot and mouth disease have occurred in many countries and regions in the world,which has become a major public health problem for children's health.There are no specific antiviral drugs for HEV71 infection,so it is necessary to develop safe and effective vaccine.In recent years,the research on HEV71 vaccine has made a breakthrough,and this article reviews the research progress of the vaccine.%人肠道病毒71型(HEV71)是引起重症手足口病的主要病原之一,感染患儿严重者可并发无菌性脑膜炎、脑干脑炎、脑脊髓炎等神经系统病变,甚至可导致死亡.近几十年来,全球多个国家和地区发生了多次大规模的手足口病暴发流行,已成为严重危害儿童健康的公共卫生问题.目前针对HEV71感染尚无特效抗病毒药物,因此研制安全有效的疫苗势在必行.近几年有关HEV71疫苗的研究取得了一定的突破,现将对该疫苗的相关研究进展作一综述.

  1. Combining cell lines to optimize isolation of human enterovirus from clinical specimens: report of 25 years of experience.

    Science.gov (United States)

    Prim, Núria; Rodríguez, Graciela; Margall, Núria; Del Cuerpo, Margarita; Trallero, Gloria; Rabella, Núria

    2013-01-01

    Cell culture is still the gold standard for the diagnosis of human enteroviruses (HEVs) although molecular techniques are required for detection of some serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to all serotypes, and several lines are required to optimize the isolation of HEVs. In this study, the results of HEV isolation during the last 25 years are reported. A total of 1,192 HEVs were isolated and isolation rates varied depending on the cell line used. MRC5 cells yielded the best results (70.7%), followed by A549 cells (52.6%), RD cells (37.5%), and HEp-2 cells (29.7%). A total of 521 HEVs were characterized, and HEV-B was the most frequent species (81%). Polioviruses (PV) and HEV-A were isolated less frequently (17% and 1%, respectively). None of the cell lines detected all the enteroviruses. MRC5 cells were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%), whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD cells and HEp2 cells, respectively. Although A549 cells did not achieve the best performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs. In view of these results, MRC5 cells, A549 cells, and RD cells should be combined to optimize isolation of HEVs. Copyright © 2012 Wiley Periodicals, Inc.

  2. mRNA decay factor AUF1 binds the internal ribosomal entry site of enterovirus 71 and inhibits virus replication.

    Directory of Open Access Journals (Sweden)

    Jing-Yi Lin

    Full Text Available AU-rich element binding factor 1 (AUF1 has a role in the replication cycles of different viruses. Here we demonstrate that AUF1 binds the internal ribosome entry site (IRES of enterovirus 71 (EV71 and negatively regulates IRES-dependent translation. During EV71 infection, AUF1 accumulates in the cytoplasm where viral replication occurs, whereas AUF1 localizes predominantly in the nucleus in mock-infected cells. AUF1 knockdown in infected cells increases IRES activity and synthesis of viral proteins. Taken together, the results suggest that AUF1 interacts with the EV71 IRES to negatively regulate viral translation and replication.

  3. Detection of enteroviruses and hepatitis a virus in water by consensus primer multiplex RT-PCR

    Institute of Scientific and Technical Information of China (English)

    Jun-Wen Li; Xin-Wei Wang; Chang-Qing Yuan; Jin-Lai Zheng; Min Jin; Nong Song; Xiu-Quan Shi; Fu-Huan Chao

    2002-01-01

    AIM: To develop a rapid detection method ofenteroviruses and Hepatitis A virus (HAV).METHODS: A one-step, single-tube consensus primersmultiplex RT-PCR was developed to simultaneouslydetect Poliovirus, Coxsackie virus, Echovirus and HAV.A general upstream primer and a HAV primer and fourdifferent sets of primers (5 primers) specific forPoliovirus, Coxsacki evirus, Echovirus and HAV cDNAwere mixed in the PCR mixture to reverse transcriptand amplify the target DNA.Four distinct amplified DNAsegments representing Poliovirus, Coxsackie virus,Echovirus and HAV were identified by gelelectrophoresis as 589-,671-, 1084-, and 1128bpsequences, respectively. Semi-nested PCR was used toconfirm the amplified products for each enterovirus andHAV.RESULTS: All four kinds of viral genome RNA weredetected, and producing four bands which could bedifferentiated by the band size on the gel.To confirmthe specificity of the multiplex PCR products, semi-nested PCR was performed. For all the four strainstested gave positive results .The detection sensitivityof multiplex PCR was similar to that of monoplex RT-PCR which was 24 PFU for Poliovrus, 21 PFU forCoxsackie virus,60 PFU for Echovirus and 105 TCID50for HAV. The minimum amount of enteric viral RNAdetected by semi-nested PCR was equivalent to 2.4 PFUfor Poliovrus, 2.1 PFU for Coxsackie virus, 6.0 PFU forEchovirus and 10.5 TCID50 for HAV.CONCLUSION: The consensus primers multiplex RT-PCRhas more advantages over monoplex RT-PCR for entericviruses detection, namely, the rapid turnaround timeand cost effectiveness.

  4. Selection and characterization of vaccine strain for Enterovirus 71 vaccine development.

    Science.gov (United States)

    Chang, Jui-Yuan; Chang, Cheng-Peng; Tsai, Hutchinson Hau-Pong; Lee, Chen-Dou; Lian, Wei-Cheng; Ih-Jen-Su; Sai, I-Hsi; Liu, Chia-Chyi; Chou, Ai-Hsiang; Lu, Ya-Jung; Chen, Ching-Yao; Lee, Pi-Hsiu; Chiang, Jen-Ron; Chong, Pele Choi-Sing

    2012-01-17

    Enterovirus 71 (EV71) has recently emerged as an important neurotropic virus in Asia because effective medications and prophylactic vaccine against EV71 infection are not available. Based on the success of inactivated poliovirus vaccine, the Vero cell-based chemically inactivated EV71 vaccine candidate could be developed. Identification of EV71 vaccine strain which can grow to high titer in Vero cell and induce cross-genotype virus neutralizing antibody responses represents the first step in vaccine development. In this report we describe the characterization and validation of a clinical isolate E59 belonging to B4 sub-genotype based on VP1 genetic analysis. Before selected as the vaccine strain, the genetic stability of E59 in passage had been analyzed based on the nucleotide sequences obtained from the Master Virus Seed, Working Seed banks and the virus harvested from the production lots, and found to be identical to those found in the original isolate. These results indicate that E59 vaccine strain has strong genetic stability in passage. Using this vaccine strain the prototype EV71 vaccine candidate was produced from 20L of Vero cell grown in serum-containing medium. The production processes were investigated, characterized and quantified to establish the potential vaccine manufacturing process including the time for virus harvest, the membrane for diafiltration and concentration, the gel-filtration chromatography for the down-stream virus purification, and the methods for viral inactivation. Finally, the inactivated virion vaccine candidate containing sub-microgram of viral proteins formulated with alum adjuvant was found to induce strong virus neutralizing antibody responses in mice and rabbits. Therefore, these results provide valuable information for cell-based EV71 vaccine development.

  5. The association between enterovirus 71 infections and meteorological parameters in Taiwan.

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    Hsiao-Ling Chang

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 infections are a significant cause of neurological disorder and death in children worldwide. Seasonal variations in EV71 infections have been recognized, but the mechanisms responsible for this phenomenon remain unknown. The purpose of this study was to examine the relationship between meteorological parameters and EV71 infection. METHODS AND FINDINGS: We analyzed the number of EV71 infections and daily climate data collected in Taiwan between 1998 and 2008 and used Poisson regression analysis and case-crossover methodology to evaluate the association between weather variability and the incidence of EV71 infection. A total of 1,914 EV71-infected patients were reported between 1998 and 2008. The incidence of EV71 infections reflected significant summertime seasonality (for oscillation, p<0.001. The incidence of EV71 infections began to rise at temperatures above 13°C (r(2 = 0.76, p<0.001; at temperatures higher than approximately 26°C (r(2 = 0.94, p<0.05, the incidence began to decline, producing an inverted V-shaped relationship. The increase in the incidence with increasing relative humidity was positive and linear (r(2 = 0.68, p<0.05. EV71 infection was most highly correlated with temperature and relative humidity in the period that likely preceded the infection. CONCLUSION: Our study provides quantitative evidence that the rate of EV71 infection increased significantly with increasing mean temperature and relative humidity in Taiwan.

  6. Diffusion-weighted imaging in the diagnosis of enterovirus 71 encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Lian, Zhou-yang; Huang, Biao; Liang, Chang-hong (Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China)), Email: cjr.huangbiao@vip.163.com; He, Shaoru; Guo, Yuxiong (Department of Pediatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong (China))

    2012-03-15

    Background. In the early phase of viral encephalitis, conventional MRI may appear normal. Diffusion-weighted imaging (DWI) is a sensitive tool for detecting early changes in cellular function in the central nervous system. Purpose. To investigate the usefulness of DWI in the diagnosis of enterovirus 71 (EV71) encephalitis, and to determine whether DWI is superior to conventional MR sequences. Material and Methods. MRI scans in 26 patients were retrospectively evaluated for distribution of lesions on T1-weighted images (T1WI), T2-weighted images (T2WI), fluid-attenuated inversion recovery (FLAIR), and DWI. Contrast-to-noise ratios (CNRs) were calculated for all regions on each sequence and differences in the four MRI sequences were assessed using CNRs. Apparent diffusion coefficient (ADC) values were measured for all regions to look for true restriction of diffusion. Results. Fifteen out of 26 cases showed positive findings on MR imaging. The brain stem was involved in 11 patients, cortex and subcortical white matter in four patients. DWI was more sensitive in detecting the abnormalities (89.7%) compared to T2WI (48.7%), FLAIR (41.0%), and T1WI (35.9%), and the positive ratio of DWI was significantly higher compared to other sequences. Furthermore, no significant difference was found between T2WI and FLAIR (P 0.649). The corresponding mean CNRs were 8.73 +- 2.57, 83.59 +- 29.28, 24.22 +- 6.22, and 132.27 +- 78.32 on T1WI, T2WI, FLAIR, and DWI, respectively. The absolute values of CNRs of lesions on DWI were significantly greater than those on other sequences. Conclusion. DWI appears to be more sensitive in detecting EV71 encephalitis than conventional MRI sequences. This capability may improve the accuracy in diagnosing EV71 encephalitis, especially at the early stage

  7. Protection against lethal enterovirus 71 challenge in mice by a recombinant vaccine candidate containing a broadly cross-neutralizing epitope within the VP2 EF loop.

    Science.gov (United States)

    Xu, Longfa; He, Delei; Li, Zhiqun; Zheng, Jun; Yang, Lisheng; Yu, Miao; Yu, Hai; Chen, Yixin; Que, Yuqiong; Shih, James Wai Kuo; Liu, Gang; Zhang, Jun; Zhao, Qinjian; Cheng, Tong; Xia, Ningshao

    2014-01-01

    Human enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD) and is associated with several severe neurological complications in the Asia-Pacific region. Here, we evaluated that while passive transfer of neutralizing monoclonal antibody (nMAb) against the VP2 protein protect against lethal EV71 infection in BALB/c mice. Protective nMAb were mapped to residues 141-155 of VP2 by peptide ELISA. High-resolution structural analysis showed that the epitope is part of the VP2 EF loop, which is the "puff" region that forms the "southern rim" of the canyon. Moreover, a three-dimensional structural characterization for the puff region with prior neutralizing epitopes and receptor-binding sites that can serve to inform vaccine strategies. Interestingly, using hepatitis B virus core protein (HBc) as a carrier, we demonstrated that the cross-neutralizing EV71 antibodies were induced, and the VP2 epitope immunized mice serum also conferred 100% in vivo passive protection. The mechanism of in vivo protection conferred by VP2 nMAb is in part attributed to the in vitro neutralizing titer and ability to bind authentic viral particles. Importantly, the anti-VP2(aa141-155) antibodies could inhibit the binding of human serum to EV71 virions showed that the VP2 epitope is immunodominant. Collectively, our results suggest that a broad-spectrum vaccine strategy targeting the high-affinity epitope of VP2 EF loop may elicits effective immune responses against EV71 infection.

  8. Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16

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    Ching-Ying Wang

    2013-01-01

    Full Text Available Enterovirus 71 (EV71 and coxsackievirus A16 (CoxA16 are main pathogens of hand-foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant and anti-inflammatory activities. Our prior report (2012 cited K. gracilis leaf extract as moderately active against EV71 and CoxA16. This study further rates antienteroviral potential of K. gracilis stem (KGS extract to identify potent antiviral fractions and components. The extract moderately inhibits viral cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 = 75.18 μg/mL and CoxA16 (IC50 = 81.41 μg/mL. Ethyl acetate (EA fraction of KGS extract showed greater antiviral activity than that of n-butanol or aqueous fraction: IC50 values of 4.21 μg/mL against EV71 and 9.08 μg/mL against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque reduction assay indicate that eupafolin is a vital component of EA fraction showing potent activity against EV71 (IC50 = 1.39 μM and CoxA16 (IC50 = 5.24 μM. Eupafolin specifically lessened virus-induced upregulation of IL-6 and RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti-enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential against EV71 and CoxA16 infection.

  9. 肠道病毒71型感染的临床研究%Cinical research of Enterovirus 71 infection

    Institute of Scientific and Technical Information of China (English)

    张忠东; 吕铁锋

    2008-01-01

    Enterovirus 71(EV71)was first idenfified in 1969.Since then,several epidemics of EV71 infection have occurred around the world.EV71 is a major causative viral agent responsible for large outbreaks of hand-foot-mouth disease(HEMD).It is often associated with neurological complications,such as aseptic meningitis,brain stem encephalitis and poliomyelitis-like paralysis and has caused high mortality in recent outbreaks.Currently.there is no effective anlivind treatment for severe EV71 infections and no vaccine is available.We need a rapid and sensitive method to detect EV71 from clinical specimens,and will allow quaranntine measures to be taken more effectively during outbreaks.This review briefly outlines the advance of EV71 infection in epidemiology,clinical manifestation,detective measures and therapy.%肠道病毒71型(EV71)自1969年首次分离出来后,已在世界范围内引起了数次爆发流行.EV71是手足口病的主要病因,常引起多种与神经系统相关的严重疾病.目前缺乏有效的抗病毒治疗和高效疫苗,故早期发现和检测尤为重要.此文就EV71感染的流行情况、临床表现、检测技术及治疗等研究作了介绍.

  10. The Construction of the EGFP Enterovirus 71%肠道病毒71型(EV71)荧光病毒的构建

    Institute of Scientific and Technical Information of China (English)

    朱守海; 王璐璐

    2014-01-01

    人肠道病毒71型(Enterovirus,EV71)是引起手足口病的主要病原体。首先利用反向遗传学的方法,构建了EV71全长cDNA感染性克隆,经体外转录、转染RD细胞后成功获得了拯救病毒。随后,将增强型绿色荧光蛋白基因(Enhanced green fluorescent protein,EGFP)插入到EV71基因组中构建荧光病毒。结果表明,此荧光病毒不仅可以侵染、复制,在传代的过程中EGFP基因也保持了较好的稳定性,表明其可以作为一种报告病毒应用于高通量的EV71抗病毒药物筛选中。%Human Enterovirus 71(EV71)is one of the major agents causing hand, foot and mouth disease(HFMD). An infectious full-length cDNA clone of EV71 as well as the recuse virus were obtained using the reverse genetic techniques. Then, the EGFP gene was inserted into the EV71 genome to construct the reporter virus. The results show that the EGFP-EV71 virus not only are replication-competent and infectious, but the EGFP gene are stable during passaging, implicating the recombinant virus could be used as a reporter virus for high throughput EV71 antiviral drugs screening.

  11. Characterization of Enteroviruses from non-human primates in cameroon revealed virus types widespread in humans along with candidate new types and species.

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    Serge Alain Sadeuh-Mba

    Full Text Available Enteroviruses (EVs infecting African Non-Human Primates (NHP are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases.

  12. The highly conserved 5' untranslated region as an effective target towards the inhibition of Enterovirus 71 replication by unmodified and appropriate 2'-modified siRNAs

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    Deng Jun-Xia

    2012-08-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 is a highly infectious agent that plays an etiological role in hand, foot, and mouth disease. It is associated with severe neurological complications and has caused significant mortalities in recent large-scale outbreaks. Currently, no effective vaccine or specific clinical therapy is available against EV71. Methods Unmodified 21 nucleotide small interfering RNAs (siRNAs and classic 2′-modified (2′-O-methylation or 2′-fluoro modification siRNAs were designed to target highly conserved 5′ untranslated region (UTR of the EV71 genome and employed as anti-EV71 agents. Real-time TaqMan RT-PCR, western blot analysis and plaque assays were carried out to evaluate specific viral inhibition by the siRNAs. Results Transfection of rhabdomyosarcoma (RD cells with siRNAs targeting the EV71 genomic 5′ UTR significantly delayed and alleviated the cytopathic effects of EV71 infection, increased cell viability in EV71-infected RD cells. The inhibitory effect on EV71 replication was sequence-specific and dosage-dependent, with significant corresponding decreases in viral RNA, VP1 protein and viral titer. Appropriate 2′-modified siRNAs exhibited similar RNA interference (RNAi activity with dramatically increased serum stability in comparison with unmodified counterparts. Conclusion Sequences were identified within the highly conserved 5′ UTR that can be targeted to effectively inhibit EV71 replication through RNAi strategies. Appropriate 2′-modified siRNAs provide a promising approach to optimizing siRNAs to overcome barriers on RNAi-based antiviral therapies for broader administration.

  13. Quantitative RT-PCR Detection of Hepatitis A Virus, Rotaviruses and Enteroviruses in the Buffalo River and Source Water Dams in the Eastern Cape Province of South Africa

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    Anthony Ifeanyi Okoh

    2012-11-01

    Full Text Available Human enteric viruses (HEntVs are a major cause of water-related diseases. The prevalence of hepatitis A virus (HAV, rotaviruses (RoV and enteroviruses (EnV in Buffalo River waters was assessed quantitatively over a period of 12 months (August 2010 to July 2011. Seventy-two samples were collected from six sites, including three dams, and concentrated using the adsorption-elution method. Viral RNA was extracted using a commercial kit, and the viruses were quantified by real-time quantitative reverse transcriptase PCR (RT-qPCR. Two or more viruses were detected in 12.5% of the samples. HAV was detected in 43.1% of the samples and in significantly (p < 0.05 varying concentrations of 1.5 × 101–1.9 × 105 genome copies/L compared to RoV and EnV, while RoVs were detected in 13.9% of samples, with concentrations ranging from 2.5 × 101–2.1 × 103 genome copies/L, and EnV were detected in 9.7% of the samples, with concentrations ranging from 1.3 × 101–8.6 × 101 genome copies/L. Only HAV was detected at all the sites, with the Bridle Drift Dam recording significantly higher (p < 0.05 concentrations. The presence of enteric viruses in Buffalo River may constitute public health risks and the incidence of HAV at all the sites could reflect both the epidemiological status of hepatitis A and HAV persistence in the water environments.

  14. Direct Detection and Identification of Enteroviruses from Faeces of Healthy Nigerian Children Using a Cell-Culture Independent RT-Seminested PCR Assay

    Science.gov (United States)

    Adewumi, Moses Olubusuyi; Coker, Bamidele Atinuke; Nudamajo, Felix Yasha; Adeniji, Johnson Adekunle

    2016-01-01

    Recently, a cell-culture independent protocol for detection of enteroviruses from clinical specimen was recommended by the WHO for surveillance alongside the previously established protocols. Here, we investigated whether this new protocol will show the same enterovirus diversity landscape as the established cell-culture dependent protocols. Faecal samples were collected from sixty apparently healthy children in Ibadan, Nigeria. Samples were resuspended in phosphate buffered saline, RNA was extracted, and the VP1 gene was amplified using WHO recommended RT-snPCR protocol. Amplicons were sequenced and sequences subjected to phylogenetic analysis. Fifteen (25%) of the 60 samples yielded the expected band size. Of the 15 amplicons sequenced, 12 were exploitable. The remaining 3 had electropherograms with multiple peaks and were unexploitable. Eleven of the 12 exploitable sequences were identified as Coxsackievirus A1 (CVA1), CVA3, CVA4, CVA8, CVA20, echovirus 32 (E32), enterovirus 71 (EV71), EVB80, and EVC99. Subsequently, the last exploitable sequence was identified as enterobacteriophage baseplate gene by nucleotide BLAST. The results of this study document the first description of molecular sequence data on CVA1, CVA8, and E32 strains present in Nigeria. The result further showed that species A enteroviruses were more commonly detected in the region when cell-culture bias is bypassed. PMID:27087810

  15. Development and implementation of real-time nucleic acid amplification for the detection of enterovirus infections in comparison to rapid culture of various clinical specimens

    NARCIS (Netherlands)

    van Doornum, G J J; Schutten, Martin; Voermans, J; Guldemeester, G J J; Niesters, H G M

    2007-01-01

    Several real-time PCR and nucleic acid sequence-based amplification (NASBA) primer pairs and a modified real-time PCR primer pair for the detection of enteroviruses were compared. The modified real-time PCR primer pair was evaluated on clinical samples in comparison with cell culture using the Magna

  16. Direct Detection and Identification of Enteroviruses from Faeces of Healthy Nigerian Children Using a Cell-Culture Independent RT-Seminested PCR Assay

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    Temitope Oluwasegun Cephas Faleye

    2016-01-01

    Full Text Available Recently, a cell-culture independent protocol for detection of enteroviruses from clinical specimen was recommended by the WHO for surveillance alongside the previously established protocols. Here, we investigated whether this new protocol will show the same enterovirus diversity landscape as the established cell-culture dependent protocols. Faecal samples were collected from sixty apparently healthy children in Ibadan, Nigeria. Samples were resuspended in phosphate buffered saline, RNA was extracted, and the VP1 gene was amplified using WHO recommended RT-snPCR protocol. Amplicons were sequenced and sequences subjected to phylogenetic analysis. Fifteen (25% of the 60 samples yielded the expected band size. Of the 15 amplicons sequenced, 12 were exploitable. The remaining 3 had electropherograms with multiple peaks and were unexploitable. Eleven of the 12 exploitable sequences were identified as Coxsackievirus A1 (CVA1, CVA3, CVA4, CVA8, CVA20, echovirus 32 (E32, enterovirus 71 (EV71, EVB80, and EVC99. Subsequently, the last exploitable sequence was identified as enterobacteriophage baseplate gene by nucleotide BLAST. The results of this study document the first description of molecular sequence data on CVA1, CVA8, and E32 strains present in Nigeria. The result further showed that species A enteroviruses were more commonly detected in the region when cell-culture bias is bypassed.

  17. Prospective comparison of the detection rates of human enterovirus and parechovirus RT-qPCR and viral culture in different pediatric specimens

    NARCIS (Netherlands)

    de Crom, S C M; Obihara, C C; de Moor, R A; Veldkamp, E J M; van Furth, A M; Rossen, J W A

    2013-01-01

    BACKGROUND: Reverse-transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) has become the gold standard for the diagnosis of human enterovirus (EV) and parechovirus (HPeV) infections. The detection rate of RT-qPCR in different pediatric body specimens has not been compared prospect

  18. Quantitative Detection of Hepatitis A Virus and Enteroviruses Near the United States-Mexico Border and Correlation with Levels of Fecal Indicator Bacteria▿

    Science.gov (United States)

    Gersberg, Richard M.; Rose, Michael A.; Robles-Sikisaka, Refugio; Dhar, Arun K.

    2006-01-01

    For decades, untreated sewage flowing northward from Tijuana, Mexico, via the Tijuana River has adversely affected the water quality of the recreational beaches of San Diego, California. We used quantitative reverse transcription-PCR to measure the levels of hepatitis A virus (HAV) and enteroviruses in coastal waters near the United States-Mexico border and compared these levels to those of the conventional fecal indicators, Escherichia coli and enterococci. Over a 2-year period from 2003 to 2005, a total of 20 samples were assayed at two sites during both wet and dry weather: the surfzone at the mouth of the Tijuana River and the surfzone near the pier at Imperial Beach (IB), California (about 2 km north of the mouth of the Tijuana River). HAV and enterovirus were detected in 79 and 93% of the wet-weather samples, respectively. HAV concentrations in these samples ranged from 105 to 30,771 viral particles/liter, and enterovirus levels ranged from 7 to 4,417 viral particles/liter. The concentrations of HAV and enterovirus were below the limit of detection for all dry weather samples collected at IB. Regression analyses showed a significant correlation between the densities of both fecal bacterial indicators and the levels of HAV (R2 > 0.61, P 0.70, P < 0.0001), a finding that supports the use of conventional bacterial indicators to predict the levels of these viruses in recreational marine waters. PMID:16980430

  19. Quantitative detection of hepatitis a virus and enteroviruses near the United States-Mexico border and correlation with levels of fecal indicator bacteria.

    Science.gov (United States)

    Gersberg, Richard M; Rose, Michael A; Robles-Sikisaka, Refugio; Dhar, Arun K

    2006-12-01

    For decades, untreated sewage flowing northward from Tijuana, Mexico, via the Tijuana River has adversely affected the water quality of the recreational beaches of San Diego, California. We used quantitative reverse transcription-PCR to measure the levels of hepatitis A virus (HAV) and enteroviruses in coastal waters near the United States-Mexico border and compared these levels to those of the conventional fecal indicators, Escherichia coli and enterococci. Over a 2-year period from 2003 to 2005, a total of 20 samples were assayed at two sites during both wet and dry weather: the surfzone at the mouth of the Tijuana River and the surfzone near the pier at Imperial Beach (IB), California (about 2 km north of the mouth of the Tijuana River). HAV and enterovirus were detected in 79 and 93% of the wet-weather samples, respectively. HAV concentrations in these samples ranged from 105 to 30,771 viral particles/liter, and enterovirus levels ranged from 7 to 4,417 viral particles/liter. The concentrations of HAV and enterovirus were below the limit of detection for all dry weather samples collected at IB. Regression analyses showed a significant correlation between the densities of both fecal bacterial indicators and the levels of HAV (R2>0.61, P0.70, P<0.0001), a finding that supports the use of conventional bacterial indicators to predict the levels of these viruses in recreational marine waters.

  20. Structure-function relationship of viral cis-acting RNA elements : the role of the OriI and OriR in enterovirus replication

    NARCIS (Netherlands)

    Ooij, Martinus Johannes Maria van

    2007-01-01

    The genus Enterovirus belongs to Picornaviridae, a family of small, non-enveloped, lytic RNA viruses. They contain a single-stranded RNA genome of positive polarity of approximately 7,500 nucleotides. A viral protein VPg is specifically linked to the 5'terminus of the viral RNA. IRES-mediated initi

  1. First Detection of an Enterovirus C99 in a Captive Chimpanzee with Acute Flaccid Paralysis, from the Tchimpounga Chimpanzee Rehabilitation Center, Republic of Congo.

    Science.gov (United States)

    Mombo, Illich Manfred; Berthet, Nicolas; Lukashev, Alexander N; Bleicker, Tobias; Brünink, Sebastian; Léger, Lucas; Atencia, Rebeca; Cox, Debby; Bouchier, Christiane; Durand, Patrick; Arnathau, Céline; Brazier, Lionel; Fair, Joseph N; Schneider, Bradley S; Drexler, Jan Felix; Prugnolle, Franck; Drosten, Christian; Renaud, François; Leroy, Eric M; Rougeron, Virginie

    2015-01-01

    Enteroviruses, members of the Picornaviridae family, are ubiquitous viruses responsible for mild to severe infections in human populations around the world. In 2010 Pointe-Noire, Republic of Congo recorded an outbreak of acute flaccid paralysis (AFP) in the humans, caused by wild poliovirus type 1 (WPV1). One month later, in the Tchimpounga sanctuary near Pointe-Noire, a chimpanzee developed signs similar to AFP, with paralysis of the lower limbs. In the present work, we sought to identify the pathogen, including viral and bacterial agents, responsible for this illness. In order to identify the causative agent, we evaluated a fecal specimen by PCR and sequencing. A Human enterovirus C, specifically of the EV-C99 type was potentially responsible for the illness in this chimpanzee. To rule out other possible causative agents, we also investigated the bacteriome and the virome using next generation sequencing. The majority of bacterial reads obtained belonged to commensal bacteria (95%), and the mammalian virus reads matched mainly with viruses of the Picornaviridae family (99%), in which enteroviruses were the most abundant (99.6%). This study thus reports the first identification of a chimpanzee presenting AFP most likely caused by an enterovirus and demonstrates once again the cross-species transmission of a human pathogen to an ape.

  2. Enterovirus infection of human islets of Langerhans affects β-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure

    NARCIS (Netherlands)

    Hodik, M; Skog, O; Lukinius, A; Isaza-Correa, J M; Kuipers, J; Giepmans, B N G; Frisk, G

    2016-01-01

    AIMS/HYPOTHESIS: In type 1 diabetes (T1D), most insulin-producing β cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus r

  3. Cross-reactive neutralizing antibody responses to enterovirus 71 infections in young children: implications for vaccine development.

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    Mei-Liang Huang

    Full Text Available BACKGROUND: Recently, enterovirus 71 (EV71 has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism. EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups (A, B and C and 11 genotypes (A, B1∼B5 and C1∼C5. In Taiwan, nationwide EV71 epidemics with different predominant genotypes occurred in 1998 (C2, 2000-2001 (B4, 2004-2005 (C4, and 2008 (B5. In this study, sera were collected to measure cross-reactive neutralizing antibody titers against different genotypes. METHODS: We collected historical sera from children who developed an EV71 infection in 1998, 2000, 2005, 2008, or 2010 and measured cross-reactive neutralizing antibody titers against all 11 EV71 genotypes. In addition, we aligned and compared the amino acid sequences of P1 proteins of the tested viruses. RESULTS: Serology data showed that children infected with genogroups B and C consistently have lower neutralizing antibody titers against genogroup A (>4-fold difference. The sequence comparisons revealed that five amino acid signatures (N143D in VP2; K18R, H116Y, D167E, and S275A in VP1 are specific for genogroup A and may be related to the observed antigenic variations. CONCLUSIONS: This study documented antigenic variations among different EV71 genogroups and identified potential immunodominant amino acid positions. Enterovirus surveillance and vaccine development should monitor these positions.

  4. Comparison of enterovirus and adenovirus concentration and enumeration methods in seawater from Southern California, USA and Baja Malibu, Mexico.

    Science.gov (United States)

    Sassoubre, Lauren M; Love, David C; Silverman, Andrea I; Nelson, Kara L; Boehm, Alexandria B

    2012-09-01

    Despite being important etiological agents of waterborne illness, the sources, transport and decay of human viruses in recreational waters are not well understood. This study examines enterovirus and adenovirus concentrations in coastal water samples collected from four beaches impacted by microbial pollution: (1) Malibu Lagoon, Malibu; (2) Tijuana River, Imperial Beach; (3) Baja Malibu, Baja California; and (4) Punta Bandera, Baja California. Water samples were concentrated using a flocculation-based skim milk method and dead-end membrane filtration (MF). Viruses were enumerated using cell culture infectivity assays and reverse transcription quantitative polymerase chain reaction (RT-QPCR). Across concentration and quantification methods, enteroviruses were detected more often than adenoviruses. For both viruses, MF followed by (RT)QPCR yielded higher concentrations than skim milk flocculation followed by (RT)QPCR or cell culture assays. Samples concentrated by skim milk flocculation and enumerated by (RT)QPCR agreed more closely with concentrations enumerated by cell culture assays than MF followed by (RT)QPCR. The detection of viruses by MF and (RT)QPCR was positively correlated with the presence of infectious viruses. Further research is needed to determine if detection of viruses by rapid methods such as (RT)QPCR can be a useful water quality monitoring tool to assess health risks in recreational waters.

  5. Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.

    Science.gov (United States)

    Hsiao, Hung-Bo; Chou, Ai-Hsiang; Lin, Su-I; Chen, I-Hua; Lien, Shu-Pei; Liu, Chia-Chyi; Chong, Pele; Liu, Shih-Jen

    2014-10-01

    Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-α/β]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of activating TLR9. We hypothesized that TLR9-activating signaling from plasmacytoid dendritic cells (pDCs) may contribute to host defense mechanisms. To test our hypothesis, Flt3 ligand-cultured DCs (Flt3L-DCs) from both wild-type (WT) and TLR9 knockout (TLR9KO) mice were infected with EV71. More viral particles were produced in TLR9KO mice than by WT mice. In contrast, alpha interferon (IFN-α), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-α), IFN-γ, interleukin 6 (IL-6), and IL-10 levels were increased in Flt3L-DCs from WT mice infected with EV71 compared with TLR9KO mice. Seven-day-old TLR9KO mice infected with a non-mouse-adapted EV71 strain developed neurological lesion-related symptoms, including hind-limb paralysis, slowness, ataxia, and lethargy, but WT mice did not present with these symptoms. Lung, brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice exhibited significantly higher viral loads than equivalent tissues collected from WT mice. Histopathologic damage was observed in brain, small intestine, forelimb, and hind-limb tissues collected from TLR9KO mice infected with EV71. Our findings demonstrate that TLR9 is an important host defense molecule during EV71 infection. Importance: The host innate immune system is equipped with pattern recognition receptors (PRRs), which are useful for defending the host

  6. Evaluation of a viral microarray based on simultaneous extraction and amplification of viral nucleotide acid for detecting human herpesviruses and enteroviruses.

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    Yi Liu

    Full Text Available In this study, a viral microarray based assay was developed to detect the human herpesviruses and enteroviruses associated with central nervous system infections, including herpes simplex virus type 1, type 2 (HSV1 and HSV2, Epstein-Barr virus (EBV, cytomegalovirus (CMV, enterovirus 71 (EV71, coxsackievirus A 16 (CA16 and B 5(CB5. The DNA polymerase gene of human herpesviruses and 5'-untranslated region of enteroviruses were selected as the targets to design primers and probes. Human herpesviruses DNA and enteroviruses RNA were extracted simultaneously by using a guanidinium thiocyanate acid buffer, and were subsequently amplified through a biotinylated asymmetry multiplex RT-PCR with the specific primer of enteroviruses. In total, 90 blood samples and 49 cerebrospinal fluids samples with suspected systemic or neurological virus infections were investigated. Out of 139 samples, 66 were identified as positive. The specificities of this multiplex RT-PCR microarray assay were over 96% but the sensitivities were various from 100% for HSV1, HSV2, EV71 and CB5, 95.83% for CMV, 80% for EBV to 71.43% for CA16 in comparison with reference standards of TaqMan qPCR/qRT-PCR. The high Kappa values (>0.90 from HSV1, HSV2, CMV, EV71 and CB5 were obtained, indicating almost perfect agreement in term of the 5 viruses detection. But lower Kappa values for EBV (0.63 and CA16 (0.74 displayed a moderate to substantial agreement. This study provides an innovation of simultaneous extraction, amplification, hybridization and detection of DNA viruses and RNA viruses with simplicity and specificity, and demonstrates a potential clinical utility for a variety of viruses' detection.

  7. Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors.

    Science.gov (United States)

    Zhang, Wei; Qiao, Haishi; Lv, Yuanzi; Wang, Jingjing; Chen, Xiaoqing; Hou, Yayi; Tan, Renxiang; Li, Erguang

    2014-01-01

    Flavonoids are widely distributed natural products with broad biological activities. Apigenin is a dietary flavonoid that has recently been demonstrated to interact with heterogeneous nuclear ribonucleoproteins (hnRNPs) and interferes with their RNA editing activity. We investigated whether apigenin possessed antiviral activity against enterovirus-71 (EV71) infection since EV71 infection requires of hnRNP proteins. We found that apigenin selectively blocks EV71 infection by disrupting viral RNA association with hnRNP A1 and A2 proteins. The estimated EC50 value for apigenin to block EV71 infection was determined at 10.3 µM, while the CC50 was estimated at 79.0 µM. The anti-EV71 activity was selective since no activity was detected against several DNA and RNA viruses. Although flavonoids in general share similar structural features, apigenin and kaempferol were among tested compounds with significant activity against EV71 infection. hnRNP proteins function as trans-acting factors regulating EV71 translation. We found that apigenin treatment did not affect EV71-induced nucleocytoplasmic redistribution of hnRNP A1 and A2 proteins. Instead, it prevented EV71 RNA association with hnRNP A1 and A2 proteins. Accordingly, suppression of hnRNP A1 and A2 expression markedly reduced EV71 infection. As a positive sense, single strand RNA virus, EV71 has a type I internal ribosome entry site (IRES) that cooperates with host factors and regulates EV71 translation. The effect of apigenin on EV71 infection was further demonstrated using a bicistronic vector that has the expression of a GFP protein under the control of EV71 5'-UTR. We found that apigenin treatment selectively suppressed the expression of GFP, but not a control gene. In addition to identification of apigenin as an antiviral agent against EV71 infection, this study also exemplifies the significance in antiviral agent discovery by targeting host factors essential for viral replication.

  8. Differential gene expressions of the MAPK signaling pathway in enterovirus 71-infected rhabdomyosarcoma cells

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    Weifeng Shi

    2013-08-01

    Full Text Available BACKGROUND: Mitogen-activated protein kinase (MAPK signaling pathway plays an important role in response to viral infection. The aim of this study was to explore the function and mechanism of MAPK signaling pathway in enterovirus 71 (EV71 infection of human rhabdomyosarcoma (RD cells. METHODS: Apoptosis of RD cells was observed using annexin V-FITC/PI binding assay under a fluorescence microscope. Cellular RNA was extracted and transcribed to cDNA. The expressions of 56 genes of MAPK signaling pathway in EV71-infected RD cells at 8 h and 20 h after infection were analyzed by PCR array. The levels of IL-2, IL-4, IL-10, and TNF-α in the supernatant of RD cells infected with EV71 at different time points were measured by ELISA. RESULTS: The viability of RD cells decreased obviously within 48 h after EV71 infection. Compared with the control group, EV71 infection resulted in the significantly enhanced releases of IL-2, IL-4, IL-10 and TNF-α from infected RD cells (p < 0.05. At 8 h after infection, the expressions of c-Jun, c-Fos, IFN-i, MEKK1, MLK3 and NIK genes in EV71-infected RD cells were up-regulated by 2.08-6.12-fold, whereas other 19 genes (e.g. AKT1, AKT2, E2F1, IKK and NF-κB1 exhibited down-regulation. However, at 20 h after infection, those MAPK signaling molecules including MEKK1, ASK1, MLK2, MLK3, NIK, MEK1, MEK2, MEK4, MEK7, ERK1, JNK1 and JNK2 were up-regulated. In addition, the expressions of AKT2, ELK1, c-Jun, c-Fos, NF-κB p65, PI3K and STAT1 were also increased. CONCLUSION: EV71 infection induces the differential gene expressions of MAPK signaling pathway such as ERK, JNK and PI3K/AKT in RD cells, which may be associated with the secretions of inflammatory cytokines and host cell apoptosis.

  9. The evolution of Vp1 gene in enterovirus C species sub-group that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.

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    Teemu Smura

    Full Text Available Genus Enterovirus (Family Picornaviridae, consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes. The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes. An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21, CVA-24, Enterovirus C95 (EV-C95, EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific 'signature' amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific 'signature' amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared.

  10. The Evolution of Vp1 Gene in Enterovirus C Species Sub-Group That Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

    Science.gov (United States)

    Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

    2014-01-01

    Genus Enterovirus (Family Picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21), CVA-24, Enterovirus C95 (EV-C95), EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific ‘signature’ amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific ‘signature’ amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent) positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared. PMID:24695547

  11. Polio eradication initiative in Africa: influence on other infectious disease surveillance development

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    Cochi Stephen

    2002-12-01

    Full Text Available Abstract Background The World Health Organization (WHO and partners are collaborating to eradicate poliomyelitis. To monitor progress, countries perform surveillance for acute flaccid paralysis (AFP. The WHO African Regional Office (WHO-AFRO and the U.S Centers for Disease Control and Prevention are also involved in strengthening infectious disease surveillance and response in Africa. We assessed whether polio-eradication initiative resources are used in the surveillance for and response to other infectious diseases in Africa. Methods During October 1999-March 2000, we developed and administered a survey questionnaire to at least one key informant from the 38 countries that regularly report on polio activities to WHO. The key informants included WHO-AFRO staff assigned to the countries and Ministry of Health personnel. Results We obtained responses from 32 (84% of the 38 countries. Thirty-one (97% of the 32 countries had designated surveillance officers for AFP surveillance, and 25 (78% used the AFP resources for the surveillance and response to other infectious diseases. In 28 (87% countries, AFP program staff combined detection for AFP and other infectious diseases. Fourteen countries (44% had used the AFP laboratory specimen transportation system to transport specimens to confirm other infectious disease outbreaks. The majority of the countries that performed AFP surveillance adequately (i.e., non polio AFP rate = 1/100,000 children aged Conclusions Despite concerns regarding the targeted nature of AFP surveillance, it is partially integrated into existing surveillance and response systems in multiple African countries. Resources provided for polio eradication should be used to improve surveillance for and response to other priority infectious diseases in Africa.

  12. Report on waterborne diseases: The polymerase chain reaction for the identification of enteric viruses in water; Rapporto sulle malattie infettive di origine idricamerizzazione a catena per l`identificazione dei virus enterici nell`acqua

    Energy Technology Data Exchange (ETDEWEB)

    Muscillo, M.; La Rosa, G. [Istituto Superiore di Sanita, Rome (Italy). Lab. di Igiene Ambientale

    1995-12-01

    A variety of human infectious diseases are associated with the pollution of water by enteric viruses. The epidemiological data on cases associated with drinking and recreational water show Norwalk, hepatitis A and E viruses, rotavirus and enteroviruses as the etiological agents. The polymerase chain reaction (PCR) is certainly the most reliable technique available for the rapid identification of these viruses in water samples.

  13. Enterovirus D68 in Viet Nam (2009-2015 [version 1; referees: 2 approved, 1 approved with reservations

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    Nguyen Thi Han Ny

    2017-06-01

    Full Text Available Background: Since 1962, enterovirus D68 (EV-D68 has been implicated in multiple outbreaks and sporadic cases of respiratory infection worldwide, but especially in the USA and Europe with an increasing frequency between 2010 and 2014. We describe the detection, associated clinical features and molecular characterization of EV-D68 in central and southern Viet Nam between 2009 and 2015. Methods: Enterovirus/rhinovirus PCR positive respiratory or CSF samples taken from children and adults with respiratory/central nervous system infections in Viet Nam were tested by an EV-D68 specific PCR. The included samples were derived from 3 different observational studies conducted at referral hospitals across central and southern Viet Nam between 2009 and 2015. Whole-genome sequencing was carried out using a MiSeq based approach. Phylogenetic reconstruction and estimation of evolutionary rate and recombination were carried out in BEAST and Recombination Detection Program, respectively. Results: EV-D68 was detected in 21/625 (3.4% enterovirus/rhinovirus PCR positive respiratory samples but in none of the 15 CSF. All the EV-D68 patients were young children (age range: 11.8 – 24.5 months and had moderate respiratory infections. Phylogenetic analysis suggested that the Vietnamese sequences clustered with those from Asian countries, of which 9 fell in the B1 clade, and the remaining sequence was identified within the A2 clade. One intra sub-clade recombination event was detected, representing the second reported recombination within EV-D68. The evolutionary rate of EV-D68 was estimated to be 5.12E-3 substitutions/site/year. Phylogenetic analysis indicated that the virus was imported into Viet Nam in 2008. Conclusions: We have demonstrated for the first time EV-D68 has been circulating at low levels in Viet Nam since 2008, associated with moderate acute respiratory infection in children. EV-D68 in Viet Nam is most closely related to Asian viruses, and clusters

  14. Performance of a Taqman Assay for Improved Detection and Quantification of Human Rhinovirus Viral Load

    Science.gov (United States)

    Ng, Kim Tien; Chook, Jack Bee; Oong, Xiang Yong; Chan, Yoke Fun; Chan, Kok Gan; Hanafi, Nik Sherina; Pang, Yong Kek; Kamarulzaman, Adeeba; Tee, Kok Keng

    2016-01-01

    Human rhinovirus (HRV) is the major aetiology of respiratory tract infections. HRV viral load assays are available but limitations that affect accurate quantification exist. We developed a one-step Taqman assay using oligonucleotides designed based on a comprehensive list of global HRV sequences. The new oligonucleotides targeting the 5′-UTR region showed high PCR efficiency (E = 99.6%, R2 = 0.996), with quantifiable viral load as low as 2 viral copies/μl. Assay evaluation using an External Quality Assessment (EQA) panel yielded a detection rate of 90%. When tested on 315 human enterovirus-positive specimens comprising at least 84 genetically distinct HRV types/serotypes (determined by the VP4/VP2 gene phylogenetic analysis), the assay detected all HRV species and types, as well as other non-polio enteroviruses. A commercial quantification kit, which failed to detect any of the EQA specimens, produced a detection rate of 13.3% (42/315) among the clinical specimens. Using the improved assay, we showed that HRV sheds in the upper respiratory tract for more than a week following acute infection. We also showed that HRV-C had a significantly higher viral load at 2–7 days after the onset of symptoms (p = 0.001). The availability of such assay is important to facilitate disease management, antiviral development, and infection control. PMID:27721388

  15. 肠道病毒分子分型研究进展%Molecular strategy for serotyping of enterovirus

    Institute of Scientific and Technical Information of China (English)

    卫海燕; 许玉玲; 黄学勇; 马宏

    2012-01-01

    肠道病毒(enterovirus,EV)属于小RNA病毒科肠道病毒属,包括脊髓灰质炎病毒( poliovirus,PV)、埃柯病毒(Echovirus)、柯萨奇病毒(CVA、CVB)、新型肠道病毒,共106个血清型.根据生物学及遗传特性将其分为4个组( species)[1]:肠道病毒A组(EV-A)包括21个血清型,肠道病毒B组(EV-B)包括60个血清型,肠道病毒C组(EV-C)包括21个血清型,将PV 3种血清型包括在内,肠道病毒D组(EV-D)包括4个血清型.

  16. Daphne Genkwa Sieb. et Zucc. Water-Soluble Extracts Act on Enterovirus 71 by Inhibiting Viral Entry

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    Chia-Wen Chang

    2012-04-01

    Full Text Available Dried flowers of Daphne genkwa Sieb. et Zucc. (Thymelaeaceae are a Chinese herbal medicine used as an abortifacient with purgative, diuretic and anti-inflammatory activities. However, the activity of this medicine against enteroviral infections has not been investigated. The water-extract of dried buds of D. genkwa Sieb. et Zucc. (DGFW was examined against various strains of enterovirus 71 (EV71 by neutralization assay, and its initial mode of action was characterized by time-of-addition assay followed by attachment and penetration assays. Pretreatment of DGFW with virus abolished viral replication, indicating that DGFW inhibits EV71 by targeting the virus. GFW exerts its anti-EV71 effects by inhibiting viral entry without producing cytotoxic side effects and thus provides a potential agent for antiviral chemotherapeutics.

  17. Identification of microRNAs Involved in the Host Response to Enterovirus 71 Infection by a Deep Sequencing Approach

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    Lunbiao Cui

    2010-01-01

    Full Text Available Role of microRNA (miRNA has been highlighted in pathogen-host interactions recently. To identify cellular miRNAs involved in the host response to enterovirus 71 (EV71 infection, we performed a comprehensive miRNA profiling in EV71-infected Hep2 cells through deep sequencing. 64 miRNAs were found whose expression levels changed for more than 2-fold in response to EV71 infection. Gene ontology analysis revealed that many of these mRNAs play roles in neurological process, immune response, and cell death pathways, which are known to be associated with the extreme virulence of EV71. To our knowledge, this is the first study on host miRNAs expression alteration response to EV71 infection. Our findings supported the hypothesis that certain miRNAs might be essential in the host-pathogen interactions.

  18. Selective human enterovirus and rhinovirus inhibitors: An overview of capsid-binding and protease-inhibiting molecules.

    Science.gov (United States)

    Shih, Shin-Ru; Chen, Shu-Jen; Hakimelahi, Gholam Hossein; Liu, Hsing-Jang; Tseng, Chen-Tso; Shia, Kak-Shan

    2004-07-01

    The absence of effective vaccines for most viral infections highlights an urgent necessity for the design and development of effective antiviral drugs. Due to the advancement in virology since the late 1980s, several key events in the viral life cycle have been well delineated and a number of molecular targets have been validated, culminating in the emergence of many new antiviral drugs in recent years. Inhibitors against enteroviruses and rhinoviruses, responsible for about half of the human common colds, are currently under active investigation. Agents targeted at either viral protein 1 (VP1), a relatively conserved capsid structure mediating viral adsorption/uncoating process, or 3C protease, which is highly conserved among different serotypes and essential for viral replication, are of great potential to become antipicornavirus drugs.

  19. Evolutionary Dynamics and Temporal/Geographical Correlates of Recombination in the Human Enterovirus Echovirus Types 9, 11, and 30▿

    Science.gov (United States)

    McWilliam Leitch, E. C.; Cabrerizo, M.; Cardosa, J.; Harvala, H.; Ivanova, O. E.; Kroes, A. C. M.; Lukashev, A.; Muir, P.; Odoom, J.; Roivainen, M.; Susi, P.; Trallero, G.; Evans, D. J.; Simmonds, P.

    2010-01-01

    The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated. These marked differences in recombination dynamics matched epidemiological patterns of periodic epidemic cycles of 2 to 3 (E9) and 5 to 6 (E30) years and the longer-term endemic pattern of E11 infections. Phylotemporal analysis using a Bayesian Markov chain Monte Carlo method, which placed recombination events within the evolutionary reconstruction of VP1, showed a close relationship with VP1 lineage expansion, with defined recombination events that correlated with their epidemiological periodicity. Whether recombination events contribute directly to changes in transmissibility that drive epidemic behavior or occur stochastically during periodic population bottlenecks is an unresolved issue vital to future understanding of enterovirus molecular epidemiology and pathogenesis. PMID:20610722

  20. Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30.

    Science.gov (United States)

    McWilliam Leitch, E C; Cabrerizo, M; Cardosa, J; Harvala, H; Ivanova, O E; Kroes, A C M; Lukashev, A; Muir, P; Odoom, J; Roivainen, M; Susi, P; Trallero, G; Evans, D J; Simmonds, P

    2010-09-01

    The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated. These marked differences in recombination dynamics matched epidemiological patterns of periodic epidemic cycles of 2 to 3 (E9) and 5 to 6 (E30) years and the longer-term endemic pattern of E11 infections. Phylotemporal analysis using a Bayesian Markov chain Monte Carlo method, which placed recombination events within the evolutionary reconstruction of VP1, showed a close relationship with VP1 lineage expansion, with defined recombination events that correlated with their epidemiological periodicity. Whether recombination events contribute directly to changes in transmissibility that drive epidemic behavior or occur stochastically during periodic population bottlenecks is an unresolved issue vital to future understanding of enterovirus molecular epidemiology and pathogenesis.

  1. Epididymitis caused by coxsackievirus A6 in association with hand, foot, and mouth disease.

    Science.gov (United States)

    Vuorinen, Tytti; Osterback, Riikka; Kuisma, Jani; Ylipalosaari, Pekka

    2014-12-01

    Coxsackievirus A6 (CV-A6) caused hand, foot, and mouth disease (HFMD) with a unique manifestation of epididymitis. The patient underwent operation due to suspicion of testicular torsion. Epididymitis was diagnosed by ultrasound examination. Enterovirus was detected from epididymal fluid by PCR and typed by partial sequencing of viral protein 1 as CV-A6. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Quantitative Detection of Hepatitis A Virus and Enteroviruses Near the United States-Mexico Border and Correlation with Levels of Fecal Indicator Bacteria▿

    OpenAIRE

    Gersberg, Richard M.; Rose, Michael A.; Robles-Sikisaka, Refugio; Dhar, Arun K.

    2006-01-01

    For decades, untreated sewage flowing northward from Tijuana, Mexico, via the Tijuana River has adversely affected the water quality of the recreational beaches of San Diego, California. We used quantitative reverse transcription-PCR to measure the levels of hepatitis A virus (HAV) and enteroviruses in coastal waters near the United States-Mexico border and compared these levels to those of the conventional fecal indicators, Escherichia coli and enterococci. Over a 2-year period from 2003 to ...

  3. Environmental Surveillance of Polioviruses in Rio de Janeiro, Brazil, in Support to the Activities of Global Polio Eradication Initiative.

    Science.gov (United States)

    de Oliveira Pereira, Joseane Simone; da Silva, Lidiane Rodrigues; de Meireles Nunes, Amanda; de Souza Oliveira, Silas; da Costa, Eliane Veiga; da Silva, Edson Elias

    2016-03-01

    Wild polioviruses still remain endemic in three countries (Afghanistan, Pakistan, and Nigeria) and re-emergency of wild polio has been reported in previously polio-free countries. Environmental surveillance has been used as a supplementary tool in monitoring the circulation of wild poliovirus (PVs) and/or vaccine-derived PVs even in the absence of acute flaccid paralysis cases. This study aimed to monitor the presence of polioviruses in wastewater samples collected at one wastewater treatment plant located in the municipality of Rio de Janeiro, Brazil. From December 2011 to June 2012 and from September to December 2012, 31 samples were collected and processed. RD and L20B cell cultures were able to isolate PVs and non-polio enteroviruses in 27/31 samples. Polioviruses were isolated in eight samples (type 1 Sabin = 1, type 2 Sabin = 5, and type 3 Sabin = 2). Vaccine-derived polioviruses were not detected nor evidence of recombination with other PVs or non-polio enterovirus serotypes were observed among the isolates. The Sabin-related serotypes 2 and 3 presented nucleotide substitutions in positions associated with the neurovirulent phenotype at the 5'-UTR. Changes in important Amino acid residues at VP1 were also observed in the serotypes 2 and 3. Environmental surveillance has been used successfully in monitoring the circulation of PVs and non-polio enteroviruses and it is of crucial importance in the final stages of the WHO global polio eradication initiative. Our results show the continuous circulation of Sabin-like PVs and non-polio enteroviruses in the analyzed area during the study period.

  4. An experimental study on the epidemiology of enteroviruses: water and soap washing of poliovirus 1--contaminated hands, its effectiveness and kinetics.

    Science.gov (United States)

    Schürmann, W; Eggers, H J

    1985-01-01

    As enteroviruses are mainly transmitted by the fecal-oral route, this study was initiated to investigate the nature of the binding of enteroviruses to human skin. Using poliovirus 1, Mahoney, we investigated the overall effectiveness of soap and water hand-washing of 1 and 5 min duration. The virus-skin interaction was studied by kinetic analysis of repeated serial washings. The following results were obtained: (1) Soap and water washing for 5 min reduced the number of infective particles on hands by 2-4 logs of ten. (2) Poliovirus binding to skin was essentially reversible. (3) Removal of virus followed a triexponential decline curve, suggesting loose, intermediate, and strong binding. (4) Washing agents more effective than soap were sand, aluminum hydroxide powder, and buffer alone, suggesting that friction was more important than emulsification. The results demonstrate the tenacity of poliovirus on skin, and offer a rationale for the epidemiology of enteroviruses on experimental grounds. From a practical point of view these results stress the need for an effective chemical hand disinfectant, particularly in hospitals.

  5. Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E.

    Science.gov (United States)

    Ho, Bing-Ching; Yu, Sung-Liang; Chen, Jeremy J W; Chang, Sui-Yuan; Yan, Bo-Shiun; Hong, Qi-Sheng; Singh, Sher; Kao, Chuan-Liang; Chen, Hsuan-Yu; Su, Kang-Yi; Li, Ker-Chau; Cheng, Chiou-Ling; Cheng, Hao-Wei; Lee, Jen-Yi; Lee, Chun-Nan; Yang, Pan-Chyr

    2011-01-20

    Viruses rely on the host translation machinery to complete their life cycles. Picornaviruses use an internal ribosome entry site to initiate cap-independent protein translation and in parallel host cap-dependent translation is shut off. This process is thought to occur primarily via cleavage of host translation initiation factors eIF4GI and eIF4GII by viral proteases. Here we describe another mechanism whereby miR-141 induced upon enterovirus infection targets the cap-dependent translation initiation factor, eIF4E, for shutoff of host protein synthesis. Knockdown of miR-141 reduces viral propagation, and silencing of eIF4E can completely reverse the inhibitory effect of the miR-141 antagomiR on viral propagation. Ectopic expression of miR-141 promotes the switch from cap-dependent to cap-independent translation. Moreover, we identified a transcription factor, EGR1, which is partly responsible for miR-141 induction in response to enterovirus infection. Our results suggest that upregulation of miR-141 upon enterovirus infection can facilitate viral propagation by expediting the translational switch.

  6. Comparing Enterovirus 71 with Coxsackievirus A16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of VP1s and VP4s

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    Sun Yu

    2011-11-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 and Coxsackievirus A16 (CA16 are two major etiological agents of Hand, Foot and Mouth Disease (HFMD. EV71 is associated with severe cases but not CA16. The mechanisms contributed to the different pathogenesis of these two viruses are unknown. VP1 and VP4 are two major structural proteins of these viruses, and should be paid close attention to. Results The sequences of vp1s from 14 EV71 and 14 CA16, and vp4s from 10 EV71 and 1 CA16 isolated in this study during 2007 to 2009 HFMD seasons were analyzed together with the corresponding sequences available in GenBank using DNAStar and MEGA 4.0. Phylogenetic analysis of complete vp1s or vp4s showed that EV71 isolated in Beijing belonged to C4 and CA16 belonged to lineage B2 (lineage C. VP1s and VP4s from 4 strains of viruses expressed in E. coli BL21 cells were used to detect IgM and IgG in human sera by Western Blot. The detection of IgM against VP1s of EV71 and CA16 showed consistent results with current infection, while none of the sera were positive against VP4s of EV71 and CA16. There was significant difference in the positive rates between EV71 VP1 and CA16 VP1 (χ2 = 5.02, P 2 = 15.30, P 2 = 26.47, P 2 = 16.78, P Conclusions EV71 and CA16 were highly diverse in the nucleotide sequences of vp1s and vp4s. The sera positive rates of VP1 and VP4 of EV71 were lower than those of CA16 respectively, which suggested a less exposure rate to EV71 than CA16 in Beijing population. Human serum antibodies detected by Western blot using VP1s and VP4s as antigen indicated that the immunological reaction to VP1 and VP4 of both EV71 and CA16 was different.

  7. The Role of VP1 Amino Acid Residue 145 of Enterovirus 71 in Viral Fitness and Pathogenesis in a Cynomolgus Monkey Model.

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    Chikako Kataoka

    2015-07-01

    Full Text Available 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 viral replication, genetic stability, and the pathogenicity of PB and non-PB strains of EV71 in a cynomolgus monkey model. Monkeys were intravenously inoculated with cDNA-derived PB and non-PB strains of EV71, EV71-02363-EG and EV71-02363-KE strains, respectively, with two amino acid differences at VP1-98 and VP1-145. Mild neurological symptoms, transient lymphocytopenia, and inflammatory cytokine responses, were found predominantly in the 02363-KE-inoculated monkeys. During the early stage of infection, viruses were frequently detected in clinical samples from 02363-KE-inoculated monkeys but rarely in samples from 02363-EG-inoculated monkeys. Histopathological analysis of central nervous system (CNS tissues at 10 days postinfection revealed that 02363-KE induced neuropathogenesis more efficiently than that induced by 02363-EG. After inoculation with 02363-EG, almost all EV71 variants detected in clinical samples, CNS, and non-CNS tissues, possessed a G to E amino acid substitution at VP1-145, suggesting a strong in vivo selection of VP1-145E variants and CNS spread presumably in a PSGL-1-independent manner. EV71 variants with VP1-145G were identified only in peripheral blood mononuclear cells in two out of four 02363-EG-inoculated monkeys. Thus, VP1-145E variants are mainly responsible for the development of viremia and neuropathogenesis in a non-human primate model, further suggesting the in vivo involvement of amino acid polymorphism at VP1-145 in cell

  8. The pulmonary edema caused by enterovirus71%肠道病毒71型致神经源性肺水肿机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    王丽娟

    2016-01-01

    肠道病毒71型(EV71)感染可引起手足口病,由于EV71的高度嗜神经性,重症者可合并中枢神经系统损害、急性肺水肿、心肺功能衰竭甚至死亡等.笔者就近年来EV71感染累及中枢神经系统导致神经源性肺水肿机制的研究进展进行简要综述.%Enterovirus 71 (EV71) infection can cause hand,foot and mouth disease,due to its neurotropic nature,severe cases can affect the central nervous system and emerge neurogenic pulmonary edema (NPE),respiratory and circulatory failure,and even lead to death.The advances in the pathogenesis of severe HFMD neurogenic pulmonary edema after EV71 infection in recent years are described.

  9. A 2 Years Follow up Study of the Spinal Cord MR Findings and Muscle Strength in Acute Flaccid Paralysis Patients Associated with Enterovirus 71 Infected Hand Foot Mouth Disease%肠道病毒71感染手足口病合并急性弛缓性麻痹的脊髓MRI表现及肌力的2年随访研究

    Institute of Scientific and Technical Information of China (English)

    程华; 尹光恒; 李航; 孙国强; 于形; 彭芸; 段晓岷; 曾津津; 王旭

    2012-01-01

    目的 探讨肠道病毒71型(EV71)感染手足口病合并急性弛缓性麻痹(AFP)的起病及恢复期的脊髓MRI特点,并观察影像学和肌力变化之间的相互关系.资料与方法 搜集2008年6至10月EV71感染手足口病合并AFP患儿8例,对其脊髓MRI表现及肌力进行2年随访观察.结果 本组8例,单侧下肢无力4例,双侧下肢无力2例,单侧上肢无力和双侧上肢无力各1例,合并脑干脑炎4例.MRI病变特异性累及脊髓前角,上肢无力累及颈膨大,下肢无力累及腰膨大,T2WI高信号.单侧肢体无力5例,其中2例为单侧脊髓前角受累,3例表现为双侧受累,患侧病变范围大,信号强度高.双侧肢体无力3例,脊髓前角病变范围大的一侧肌力下降明显.2年后复查,8例均表现脊髓前角病变范围减小,肌力提高者10肢,肌力下降1肢,新出现肌力下降者1肢.T,WI呈高信号及稍高信号6例,肌力均达4级以上,呈脑脊液信号2例,肌力未达4级.结论 脊髓MRI是诊断和随诊EV71感染手足口病合并AFP的最佳影像学检查方法.起病时病变累及脊髓前角区,单侧或双侧受累,以一侧为主多见.恢复期病变范围均有不同程度吸收,多数病变T2WI信号减低.起病时病变范围与肌力下降程度相一致,恢复期T2WI病变区仍呈脑脊液信号者肌力恢复较差.脊髓MRI对EV71感染手足口病合并AFP的临床预后评估具有一定的价值.%Objective To investigate the MR imaging characteristics of the spinal cord in the onset and recovery stages of the acute flaccid paralysis (AFP) patients associated with EV71 infected Hand Foot Mouth disease( HFMD) , and to ob-serve the relationship between the imaging appearance and muscle strength. Materials and Methods 8 cases of AFP as-sociated with EV71 infected HFMD were collected from June to October in 2008. The MRI findings of spinal cord and the muscle strength were followed up for 2 years. Results 4 of 8 patients had unilateral lower limb

  10. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi;

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  11. Viral etiology of aseptic meningitis among children in southern Iran.

    Science.gov (United States)

    Hosseininasab, Ali; Alborzi, Abdolvahab; Ziyaeyan, Mazyar; Jamalidoust, Marzieh; Moeini, Mahsa; Pouladfar, Gholamreza; Abbasian, Amin; Kadivar, Mohamad Rahim

    2011-05-01

    Aseptic meningitis refers to a clinical syndrome of meningeal inflammation in which bacteria cannot be identified in the cerebrospinal fluid (CSF). The viral etiology and the epidemiological, clinical, and laboratory characteristics of aseptic meningitis among children aged 2 months to 15 years in Shiraz, southern Iran were determined. From May 2007 to April 2008, 65 patients were admitted to the hospital with aseptic meningitis. Seven viruses, non-polio human enteroviruses, mumps virus, herpes simplex virus (HSV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus type 6 (HHV-6), and Epstein-Barr virus (EBV) were investigated by polymerase chain reaction (PCR) method. Viruses were detected in 30 (46.2%) patients in whom non-polio human enterovirus and mumps virus were detected in 13 (43.3%) and 11 (36.7%), respectively. The remaining 6 (20%) of the cases were caused by HSV, VZV, HCMV, and HHV-6. Haemophilus influenzae and non-polio human enterovirus were detected in one patient simultaneously. Viral meningitis was found to be more frequent during spring and summer. The majority (66.6%) of the patients were treated in the hospital for 10 days and had received antibiotics in the case of bacterial meningitis. Rapid diagnosis of viral meningitis using PCR testing of CSF can help shorten hospitalization, and avoid the unnecessary use of antibiotics.

  12. Development of a reverse transcription-loop-mediated isothermal amplification (RT-LAMP system for a highly sensitive detection of enterovirus in the stool samples of acute flaccid paralysis cases

    Directory of Open Access Journals (Sweden)

    Wakita Takaji

    2009-12-01

    Full Text Available Abstract Background In the global eradication program for poliomyelitis, the laboratory diagnosis plays a critical role by isolating poliovirus (PV from the stool samples of acute flaccid paralysis (AFP cases. In this study, we developed a reverse transcription-loop-mediated isothermal amplification (RT-LAMP system for a rapid and highly sensitive detection of enterovirus including PV to identify stool samples positive for enterovirus including PV. Methods A primer set was designed for RT-LAMP to detect enterovirus preferably those with PV-like 5'NTRs of the viral genome. The sensitivity of RT-LAMP system was evaluated with prototype strains of enterovirus. Detection of enterovirus from stool extracts was examined by using RT-LAMP system. Results We detected at least 400 copies of the viral genomes of PV(Sabin strains within 90 min by RT-LAMP with the primer set. This RT-LAMP system showed a preference for Human enterovirus species C (HEV-C strains including PV, but exhibited less sensitivity to the prototype strains of HEV-A and HEV-B (detection limits of 7,400 to 28,000 copies. Stool extracts, from which PV, HEV-C, or HEV-A was isolated in the cell culture system, were mostly positive by RT-LAMP method (positive rates of 15/16 (= 94%, 13/14 (= 93%, and 4/4 (= 100%, respectively. The positive rate of this RT-LAMP system for stool extracts from which HEV-B was isolated was lower than that of HEV-C (positive rate of 11/21 (= 52%. In the stool samples, which were negative for enterovirus isolation by the cell culture system, we found that two samples were positive for RT-LAMP (positive rates of 2/38 (= 5.3%. In these samples, enterovirus 96 was identified by sequence analysis utilizing a seminested PCR system. Conclusions RT-LAMP system developed in this study showed a high sensitivity comparable to that of the cell culture system for the detection of PV, HEV-A, and HEV-C, but less sensitivity to HEV-B. This RT-LAMP system would be useful for the

  13. Recombination in the evolution of enterovirus C species sub-group that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.

    Directory of Open Access Journals (Sweden)

    Teemu Smura

    Full Text Available Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus. However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A-C. In this study, the recombination pattern of EV-C species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99 was determined using partial 5'UTR and VP1 sequences of enterovirus strains isolated during poliovirus surveillance and previously published complete genome sequences. Several inter-typic recombination events were detected. Furthermore, the analyses suggested that inter-typic recombination events have occurred mainly within the distinct sub-groups of EV-C species. Only sporadic recombination events between EV-C species sub-group B and other EV-C sub-groups were detected. In addition, strict recombination barriers were inferred for CVA-21 genotype C and CVA-24 variant strains. These results suggest that the frequency of inter-typic recombinations, even within species, may depend on the phylogenetic position of the given viruses.

  14. Recombination in the Evolution of Enterovirus C Species Sub-Group that Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

    Science.gov (United States)

    Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

    2014-01-01

    Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus). However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C) species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A–C). In this study, the recombination pattern of EV-C species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99 was determined using partial 5′UTR and VP1 sequences of enterovirus strains isolated during poliovirus surveillance and previously published complete genome sequences. Several inter-typic recombination events were detected. Furthermore, the analyses suggested that inter-typic recombination events have occurred mainly within the distinct sub-groups of EV-C species. Only sporadic recombination events between EV-C species sub-group B and other EV-C sub-groups were detected. In addition, strict recombination barriers were inferred for CVA-21 genotype C and CVA-24 variant strains. These results suggest that the frequency of inter-typic recombinations, even within species, may depend on the phylogenetic position of the given viruses. PMID:24722726

  15. New Findings, Classification and Long-Term Follow-Up Study Based on MRI Characterization of Brainstem Encephalitis Induced by Enterovirus 71

    Science.gov (United States)

    Wen, Feiqiu; Huang, Wenxian; Gan, Yungen; Zeng, Weibin; Chen, Ranran; He, Yanxia; Wang, Yonker; Liu, Zaiyi; Liang, Changhong; Wong, Kelvin K. L.

    2016-01-01

    Background To report the diversity of MRI features of brainstem encephalitis (BE) induced by Enterovirus 71. This is supported by implementation and testing of our new classification scheme in order to improve the diagnostic level on this specific disease. Methods Neuroimaging of 91 pediatric patients who got EV71 related BE were hospitalized between March, 2010 to October, 2012, were analyzed retrospectively. All patients underwent pre- and post-contrast MRI scan. Thereafter, 31 patients were randomly called back for follow-up MRI study during December 2013 to August 2014. The MRI signal patterns of BE primary lesion were analyzed and classified according to MR signal alteration at various disease stages. Findings in fatal and non-fatal cases were compared, and according to the MRI scan time point during the course of this disease, the patients’ conditions were classified as 1) acute stage, 2) convalescence stage, 3) post mortem stage, and 4) long term follow-up study. Results 103 patients were identified. 11 patients did not undergo MRI, as they died within 48 hours. One patient died on 14th day without MR imaging. 2 patients had postmortem MRI. Medical records and imaging were reviewed in the 91 patients, aged 4 months to 12 years, and two cadavers who have had MRI scan. At acute stage: the most frequent pattern (40 patients) was foci of prolonged T1 and T2 signal, with (15) or without (25) contrast enhancement. We observed a novel pattern in 4 patients having foci of low signal intensity on T2WI, with contrast enhancement. Another pattern in 10 patients having foci of contrast enhancement without abnormalities in T1WI or T2WI weighted images. Based on 2 cases, the entire medulla and pons had prolonged T1 and T2 signal, and 2 of our postmortem cases demonstrated the same pattern. At convalescence stage, the pattern observed in 4 patients was foci of prolonged T1 and T2 signal without contrast enhancement. Follow-up MR study of 31 cases showed normal in 26

  16. Infecciones del sistema nervioso central por enterovirus en niños atendidos en un hospital de Lima, Perú Enteroviral central nervous system infections in children treated at a hospital in Lima, Peru

    Directory of Open Access Journals (Sweden)

    Iván O Espinoza

    2011-12-01

    Full Text Available Objetivos. Determinar la frecuencia y las características clínicas de las infecciones del sistema nervioso central por enterovirus en niños atendidos en el Hospital Nacional Cayetano Heredia de Lima, Perú. Materiales y métodos. Se realizó un estudio prospectivo y descriptivo desde abril 2008 hasta marzo 2010. Se enrolaron pacientes de un mes a 14 años con diagnóstico clínico de encefalitis o meningitis asépticas. Se investigó la presencia de enterovirus, virus herpes simple 1 (VHS-1, virus herpes simple 2 (VHS-2 y virus varicela-zoster (VZV mediante reacción en cadena de polimerasa (PCR. Resultados. Se enrolaron 97 pacientes de los cuales 69 % presentaron encefalitis aguda y 31 % meningitis aguda. Se identificó enterovirus en 52,6 % del total de infecciones agudas no bacterianas del sistema nervioso central; encontrándose en 83,3 % de las meningitis y en 38,8 % de las encefalitis. No hubo casos de infección por VHS-1, VHS-2 ni VZV. Las infecciones por enterovirus alcanzaron el 82,9 % en los meses cálidos de noviembre a enero y el 28,6 % en los meses fríos de mayo a julio. Conclusiones. Los enterovirus fueron los principales agentes etiológicos en las encefalitis y meningitis asépticas agudas en pacientes pediátricos de Lima, Perú. Los enterovirus tienen un comportamiento epidemiológico estacional con un claro aumento del número de casos en los meses de verano. Resulta útil tener disponible un método de diagnóstico rápido, como una ayuda para el manejo de las infecciones agudas del sistema nervioso.Objectives. To determine the frequency and clinical features of central nervous system infections caused by enterovirus in children treated at the Hospital Nacional Cayetano Heredia in Lima, Peru. Materials and methods. A prospective, descriptive study was performed from April 2008 to March 2010. Patients aged 1 month - 14 years with clinical diagnosis of encephalitis or aseptic meningitis were included. We investigated the

  17. Effect of enterovirus D68 on Lung Clearance Index in patients with cystic fibrosis: A case report

    Directory of Open Access Journals (Sweden)

    Danielle M. Goetz

    2015-01-01

    Full Text Available Cystic fibrosis (CF causes airways obstruction and a decline in percent predicted forced expiratory volume in 1 s (FEV1%. FEV1% is an objective measure of a pulmonary exacerbation of CF; improvement in FEV1% is the endpoint used often to determine success of treatment of these acute declines in pulmonary health. Lung Clearance Index (LCI, derived from multiple breath inert gas washout (MBW test, measures ventilation inhomogeneity and small airways dysfunction. In the United States in 2014–2015, enterovirus D68 (EV-D68, a novel virus, led to hospitalizations in children because of respiratory distress. This report describes 2 patients with CF admitted for pulmonary exacerbations who were enrolled in an inpatient study to assess patient satisfaction and utility of MBW to measure LCI. Diagnostic testing indicated that these patients were infected with EV-D68. Although their FEV1% improved to their previous baseline following treatment for pulmonary exacerbation, it was discordant with LCI. We discuss LCI as a novel measure of pulmonary function and hypothesize that, based on these cases, it may be a more sensitive indicator of ongoing post-viral airways dysfunction as compared to FEV1%.

  18. CD4 T-Cell-Independent Antibody Response Reduces Enterovirus 71 Lethality in Mice by Decreasing Tissue Viral Loads

    Directory of Open Access Journals (Sweden)

    Li-Chiu Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 has induced fatal encephalitis in hundreds of thousands of infants and young children in the Asia-Pacific region since the past decade. Lymphocyte and antibody responses have been suspected to aggravate EV71-induced neurological symptoms, so anti-inflammatory agents have been used to treat patients with neurological symptoms. In the present study, we found that mice deficient in CD4+ T cells were resistant to EV71 infection as wild-type mice, whereas mice deficient in B cells were highly susceptible to viral infection. Compensation of CD4 T-cell function by other immune cells was not likely, because wild-type mice depleted of CD4+ T cells were also resistant to viral infection. Infected CD4 T-cell-deficient mice produced virus-specific neutralizing antibodies, IgM and IgG. Moreover, adoptive transfer of the virus-specific antibody produced by infected CD4 T-cell-deficient mice protected B-cell-deficient mice from infection by reducing tissue viral loads. Collectively, our results show that the CD4 T-cell-independent antibody response promotes the survival of EV71-infected mice and suggest great potential for the use of vaccines and neutralizing antibodies to reduce fatal symptoms in patients.

  19. Structures of Enterovirus 71 3C proteinase (strain E2004104-TW-CDC) and its complex with rupintrivir.

    Science.gov (United States)

    Wu, Caiming; Cai, Qixu; Chen, Chen; Li, Ning; Peng, Xuanjia; Cai, Yaxian; Yin, Ke; Chen, Xinsheng; Wang, Xiaolong; Zhang, Rongfu; Liu, Lijie; Chen, Shuhui; Li, Jian; Lin, Tianwei

    2013-05-01

    The crystal structure of 3C proteinase (3C(pro)) from Enterovirus 71 (EV71) was determined in space group C2221 to 2.2 Å resolution. The fold was similar to that of 3C(pro) from other picornaviruses, but the difference in the β-ribbon reported in a previous structure was not observed. This β-ribbon was folded over the substrate-binding cleft and constituted part of the essential binding sites for interaction with the substrate. The structure of its complex with rupintrivir (AG7088), a peptidomimetic inhibitor, was also characterized in space group P212121 to 1.96 Å resolution. The inhibitor was accommodated without any spatial hindrance despite the more constricted binding site; this was confirmed by functional assays, in which the inhibitor showed comparable potency towards EV71 3C(pro) and human rhinovirus 3C(pro), which is the target that rupintrivir was designed against.

  20. Progress in Research on Enterovirus Type 71%肠道病毒71型研究进展

    Institute of Scientific and Technical Information of China (English)

    李晶华; 方小楠

    2011-01-01

    @@ 1概述 肠道病毒71型(Human enterovirus 71,EV71)于1969年首次从美国加利福尼亚患有中枢神经系统疾病的婴儿粪便标本中分离出来[1],之后多次引起的世界性的暴发流行,尤其在欧洲和亚洲国家或地区发病率极高(例如1975年在保加利亚、1978年在匈牙利、1997年在马来西亚、1998年和2008年在中国台湾都引起暴发与流行).该病毒可在恒河猴肾脏细胞(Rhesus monkey kidney cell;RhMK)及人胚二倍体细胞(Human fetal diploid cell)中分离培养.在电子显微镜下观察,这些毒株的形态与已知的其他肠道病毒极为相似,但进行中和抗体试验(Neutralization test)或免疫扩散试验(Immuno diffusion test),发现其彼此间并没有交互作用的现象,

  1. A single nucleotide in stem loop II of 5'-untranslated region contributes to virulence of enterovirus 71 in mice.

    Directory of Open Access Journals (Sweden)

    Ming-Te Yeh

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored. PRINCIPAL FINDINGS: In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL II of 237 5'-untranslated region (UTR visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo. CONCLUSIONS: These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates.

  2. Systematic community- and hospital-based surveillance for enterovirus-D68 in three Canadian provinces, August to December 2014.

    Science.gov (United States)

    Skowronski, Danuta M; Chambers, Catharine; Sabaiduc, Suzana; Murti, Michelle; Gustafson, Reka; Pollock, Sue; Hoyano, Dee; Rempel, Shirley; Allison, Sandra; De Serres, Gaston; Dickinson, James A; Tellier, Raymond; Fonseca, Kevin; Drews, Steven J; Martineau, Christine; Reyes-Domingo, Francesca; Wong, Tom; Tang, Patrick; Krajden, Mel

    2015-01-01

    Respiratory specimens collected from outpatients with influenza-like illness in three Canadian provinces (British Columbia (BC), Alberta and Quebec) participating in a community-based sentinel surveillance network were prospectively screened for enterovirus-D68 (EV-D68) from 1 August to 31 December 2014 and compared to specimens collected from 1 October 2013 to 31 July 2014. Eighteen (1%) of 1,894 specimens were EV-D68-positive: 1/348 (0.3%) collected from October to December 2013 and 11/460 (2.4%) from October to December 2014, an eight-fold increase in detection rates (p=0.01), consistent with epidemic circulation in autumn 2014. The remaining EV-D68 detections were in September 2014 (6/37). Enhanced passive surveillance was also conducted on all inpatient and outpatient EV-D68 cases (n=211) detected at the BC provincial reference laboratory from 28 August to 31 December 2014. Incidence of hospitalisations was 3/100,000 overall and 21, 17, 4 and 1/100,000 among those1 among paediatric but not adult cases. Three cases in BC with comorbidity or co-infection died and five exhibited neurological features persisting >9 months. Active surveillance in outpatient and inpatient settings is needed from more areas and additional seasons to better understand EV-D68 epidemiology and potential at-risk groups for severe or unusual manifestations.

  3. Fever without apparent source on clinical examination, lower respiratory infections in children, and enterovirus infections.

    Science.gov (United States)

    McCarthy, P L; Klig, J E; Kennedy, W P; Kahn, J S

    2000-02-01

    This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. Klig reviews recent literature about lower respiratory tract infection in children. Finally, Kennedy and Kahn discuss recent developments in infectious diseases pertinent to office practice.

  4. A rapid and efficient method for studies of virus interaction at the host cell surface using enteroviruses and real-time PCR

    Directory of Open Access Journals (Sweden)

    Israelsson Stina

    2009-12-01

    Full Text Available Abstract Background Measuring virus attachment to host cells is of great importance when trying to identify novel receptors. The presence of a usable receptor is a major determinant of viral host range and cell tropism. Furthermore, identification of appropriate receptors is central for the understanding of viral pathogenesis and gives possibilities to develop antiviral drugs. Attachment is presently measured using radiolabeled and subsequently gradient purified viruses. Traditional methods are expensive and time-consuming and not all viruses are stable during a purification procedure; hence there is room for improvement. Real-time PCR (RT-PCR has become the standard method to detect and quantify virus infections, including enteroviruses, in clinical samples. For instance, primers directed to the highly conserved 5' untranslated region (5'UTR of the enterovirus genome enable detection of a wide spectrum of enteroviruses. Here, we evaluate the capacity of the RT-PCR technology to study enterovirus host cell interactions at the cell surface and compare this novel implementation with an established assay using radiolabeled viruses. Results Both purified and crude viral extracts of CVB5 generated comparable results in attachment studies when analyzed with RT-PCR. In addition, receptor binding studies regarding viruses with coxsackie- and adenovirus receptor (CAR and/or decay accelerating factor (DAF affinity, further demonstrated the possibility to use RT-PCR to measure virus attachment to host cells. Furthermore, the RT-PCR technology and crude viral extracts was used to study attachment with low multiplicity of infection (0.05 × 10-4TCID50/cell and low cell numbers (250, which implies the range of potential implementations of the presented technique. Conclusion We have implemented the well-established RT-PCR technique to measure viral attachment to host cells with high accuracy and reproducibility, at low cost and with less effort than

  5. Clinical analysis of 18 children with enterovirus 71 infection%肠道病毒71型感染18例临床分析

    Institute of Scientific and Technical Information of China (English)

    黄全发; 邓皓辉; 叶毅桦; 陈志凤; 曾伟斌; 张素芬; 李锐钦; 张若愚

    2009-01-01

    目的 探讨儿童肠道病毒71型(EV71)感染的临床特征.方法 回顾性分析我院2008年4月至7月间18例EV71感染病例的流行病学特征及临床表现.结果 发病年龄以3岁以下为主(89%),外地移居儿童发病率明显高于本地儿童.所有患儿均出现发热及皮疹(100%),合并肺炎5例(28%),肺水肿并肺出血2例(11%),心肌炎5例(28%),病毒性脑炎4例(22%).治愈13例,好转2例,自动出院1例,死亡2例.结论 重症病例主要由EV71感染引起;肢体抖动、膝反射亢进是重症病例较具特征的表现;白细胞增高、血糖升高对危重病例的早期发现有提示意义.%Objective To study the clinical characteristics of enterovirus 71 infection in children. Methods A retrospective analysis was conducted to study the enterovirus 71 infection prevalence and clini-cal characteristics of our hospital during the period from April to July 2008. Results The onset age of most cases (89%) was below 3 years. Migrant children showed higher incidence than local children. All children had fever and skin rash (100%),5 cases were combined with pneumonia (28%),2 cases with pulmonary e-dema and pulmonary hemorrhage (11%) ,5 cases with myocarditis (28%) ,4 cases with viral encephalitis (22%). 13 cases were cured,2 cases showed improved signs and symptoms of enterovirus 71 infection, 1 case quitted and 2 cases died. Conclusion Severe cases are mainly caused by enterovirus 71. Jitter limbs and knee jerk hyperreflexia are characteristic in severe cases;higher WBC count and blood glucose rise are indica-tive for severe cases.

  6. Surveillance of the enterovirus type 71 in Shenzhen in 2000%2000年深圳市肠道病毒71型的监测

    Institute of Scientific and Technical Information of China (English)

    何雅青; 杨洪; 丰素娟; 严志平

    2003-01-01

    @@ 肠道病毒71型(enterovirus type 71; EV 71)的感染可导致多种临床症状,EV 71可以引起发热性疾病、手足口病、疱疹性咽峡炎、无菌性脑膜炎、脑炎、脑干脑炎、肺水肿、脊髓灰质炎样的麻痹性疾病等多种疾病,甚至导致死亡。

  7. Screening and detection of human enterovirus 71 infection by a real-time RT-PCR assay in Marseille, France, 2009-2011

    OpenAIRE

    Tan, C. Y. Q.; Gonfrier, G.; Ninove, L.; Zandotti, C.; Dubot Pérès, Audrey; De Lamballerie, Xavier; Charrel, R.N.

    2012-01-01

    Enterovirus-positive samples diagnosed in Marseille (January 2009 to September 2011) were screened for EV71 by real-time RT-PCR. EV71 was detected in three children below the age of 2 years with no history of overseas travel; two of these cases were associated with severe clinical presentation. Viruses demonstrated genetic similarity to other European genogroup C2 strains. Strain MRS/09/3663 complete sequencing revealed 97.6% identity across the entire genome with a 2008 Singapore isolate, wi...

  8. High rates of detection of respiratory viruses in tonsillar tissues from children with chronic adenotonsillar disease.

    Science.gov (United States)

    Proenca-Modena, Jose Luiz; Pereira Valera, Fabiana Cardoso; Jacob, Marcos Gerhardinger; Buzatto, Guilherme Pietrucci; Saturno, Tamara Honorato; Lopes, Lucia; Souza, Jamila Mendonça; Escremim Paula, Flavia; Silva, Maria Lucia; Carenzi, Lucas Rodrigues; Tamashiro, Edwin; Arruda, Eurico; Anselmo-Lima, Wilma Terezinha

    2012-01-01

    Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR) in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05), and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05) in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.

  9. High rates of detection of respiratory viruses in tonsillar tissues from children with chronic adenotonsillar disease.

    Directory of Open Access Journals (Sweden)

    Jose Luiz Proenca-Modena

    Full Text Available Chronic tonsillar diseases are an important health problem, leading to large numbers of surgical procedures worldwide. Little is known about pathogenesis of these diseases. In order to investigate the role of respiratory viruses in chronic adenotonsillar diseases, we developed a cross-sectional study to determine the rates of viral detections of common respiratory viruses detected by TaqMan real time PCR (qPCR in nasopharyngeal secretions, tonsillar tissues and peripheral blood from 121 children with chronic tonsillar diseases, without symptoms of acute respiratory infections. At least one respiratory virus was detected in 97.5% of patients. The viral co-infection rate was 69.5%. The most frequently detected viruses were human adenovirus in 47.1%, human enterovirus in 40.5%, human rhinovirus in 38%, human bocavirus in 29.8%, human metapneumovirus in 17.4% and human respiratory syncytial virus in 15.7%. Results of qPCR varied widely between sample sites: human adenovirus, human bocavirus and human enterovirus were predominantly detected in tissues, while human rhinovirus was more frequently detected in secretions. Rates of virus detection were remarkably high in tonsil tissues: over 85% in adenoids and close to 70% in palatine tonsils. In addition, overall virus detection rates were higher in more hypertrophic than in smaller adenoids (p = 0.05, and in the particular case of human enteroviruses, they were detected more frequently (p = 0.05 in larger palatine tonsils than in smaller ones. While persistence/latency of DNA viruses in tonsillar tissues has been documented, such is not the case of RNA viruses. Respiratory viruses are highly prevalent in adenoids and palatine tonsils of patients with chronic tonsillar diseases, and persistence of these viruses in tonsils may stimulate chronic inflammation and play a role in the pathogenesis of these diseases.

  10. Absence of persistent infection with enteroviruses in muscles of patients with inflammatory myopathies.

    Science.gov (United States)

    Leon-Monzon, M; Dalakas, M C

    1992-08-01

    We searched for enteroviral nucleic acid sequences using the polymerase chain reaction and slot-blot hybridization in coded muscle biopsy specimens from 39 patients with active inflammatory myopathies (polymyositis, dermatomyositis, and inclusion-body myositis) and from 16 patients with other neuromuscular diseases, including patients with postpolio syndrome. For primers, we used sequences of the noncoding region at the 5' end of the viral RNA. We failed to detect specific enteroviral nucleic acid sequences in the muscle biopsy specimens. Because this sensitive technique can amplify even low copy numbers of the viral genome, it appears unlikely that a persistent enteroviral infection is the cause of inflammatory myopathies.

  11. 免疫球蛋白对EV71染毒乳鼠的治疗作用%Investigation of Specific Immunoglobulin Against Enterovirus 71 in Infant Rats

    Institute of Scientific and Technical Information of China (English)

    董皎; 段卫华; 刘宁

    2011-01-01

    Objective To investigate the effect of immunoglobulin on enterovirus 71 in infectious rats in which was simulated. Methods An enterovirus 71 infection model rats was employed to verify the effect of a certain specific immunoglobulin injection which had high antibody-neutralizing activity with the common immunoglobulin injection used as control. Results Both the common immunoglobulin and the specific immunoglobulin had positive effect against enterovirus 71 infection if administrated immediately in vitro and in vivo . Within 24 h after enterovirus 71 infection, the specific immunoglobulin worked in a dose-dependent manner, but it failed to work if infection lasted more than 72 h. Conclusion The specific immunoglobulin can defend against enterovirus 71 infection effectively if administrated as soon as possible.%目的 考察人免疫球蛋白对肠病毒EV71型感染小鼠的治疗作用.方法 注射EV71病毒制作动物模型,以静脉用人免疫球蛋白为对照,观察不同给药时间和不同效价的特异免疫球蛋白抗EV71病毒感染的作用.结果 染毒1h内给药,不论人免疫球蛋白或特异免疫球蛋白,都能有效地抗EV71感染;24 h内给药时,特异免疫球蛋白治疗EV71病毒感染的作用有剂量依赖性.但72 h以后给药未见有效.结论 特异免疫球蛋白及时给药能有效地治疗EV71感染.

  12. Viral meningitis epidemics and a single, recent, recombinant and anthroponotic origin of swine vesicular disease virus

    DEFF Research Database (Denmark)

    Bruhn, Christian Anders Wathne; Nielsen, Sandra Cathrine Abel; Samaniego Castruita, Jose Alfredo;

    2015-01-01

    BACKGROUND AND OBJECTIVES: Swine vesicular disease virus (SVDV) is a close relative of the human Enterovirus B serotype, coxsackievirus B5. As the etiological agent of a significant emergent veterinary disease, several studies have attempted to explain its origin. However, several key questions r...... stating that SVDV originated through co-infection, recombination, and a single anthroponotic event, during large viral meningitis epidemics around 1960/1961 involving the ancestral serotypes. The exact geographical origin of SVDV may remain untestable due to historical aspects....

  13. Enterovirus 71 2B Induces Cell Apoptosis by Directly Inducing the Conformational Activation of the Proapoptotic Protein Bax.

    Science.gov (United States)

    Cong, Haolong; Du, Ning; Yang, Yang; Song, Lei; Zhang, Wenliang; Tien, Po

    2016-11-01

    To survive and replicate within a host, many viruses have evolved strategies that target crucial components within the apoptotic cascade, leading to either inhibition or induction of cell apoptosis. Enterovirus 71 (EV71) infections have been demonstrated to impact the mitochondrial apoptotic pathway and induce apoptosis in many cell lines. However, the detailed mechanism of EV71-induced apoptosis remains to be elucidated. In this study, we report that EV71 2B protein (2B) localized to the mitochondria and induced cell apoptosis by interacting directly with and activating the proapoptotic protein Bax. 2B recruited Bax to the mitochondria and induced Bax conformational activation. In addition, mitochondria isolated from 2B-expressing cells that were treated with a recombinant Bax showed increased Bax interaction and cytochrome c (Cyt c) release. Importantly, apoptosis in cells with either EV71 infection or 2B expression was dramatically reduced in Bax knockdown cells but not in Bak knockdown cells, suggesting that Bax played a pivotal role in EV71- or 2B-induced apoptosis. Further studies indicate that a hydrophobic region of 18 amino acids (aa) in the C-terminal region of 2B (aa 63 to 80) was responsible for the location of 2B in the mitochondria. A hydrophilic region of 14 aa in the N-terminal region of 2B was functional in Bax interaction and its subsequent activation. Moreover, overexpression of the antiapoptotic protein Bcl-XL abrogates 2B-induced release of Cyt c and caspase activation. Therefore, this study provides direct evidence that EV71 2B induces cell apoptosis and impacts the mitochondrial apoptotic pathway by directly modulating the redistribution and activation of proapoptotic protein Bax. EV71 infections are usually accompanied by severe neurological complications. It has also been postulated that the induction of cell apoptosis resulting from tissue damage is a possible process of EV71-related pathogenesis. In this study, we report that EV71 2B

  14. Enterovirus 71 3C protease cleaves a novel target CstF-64 and i