关键词： Adenosine triphosphatase   Crystal structure   Zinc   Protein folding   RNA structure   Cysteine   Helicases   Molecular mass  

摘要： Poliovirus (PV) 2C(ATPase) is the most studied 2C protein in the Picornaviridae family. It is involved in RNA replication, encapsidation and uncoating and many inhibitors have been found that target PV 2C(ATPase). Despite numerous investigations to characterize its functions, a high-resolution structure of PV 2C has not yet been determined. We report here the crystal structure of a soluble fragment of PV 2C(ATPase) to 2.55 angstrom, containing an ATPase domain, a zinc finger and a C-terminal helical domain but missing the N-terminal domain. The ATPase domain shares the common structural features with EV71 2C and other Superfamily 3 helicases. The C-terminal cysteine-rich motif folds into a CCCC type zinc finger in which four cysteine ligands and several auxiliary residues assist in zinc binding. By comparing with the known zinc finger fold groups, we found the zinc finger of 2C proteins belong to a new fold group, which we denote the "Enterovirus 2C-like" group. The C-terminus of PV 2C(ATPase) forms an amphipathic helix that occupies a hydrophobic pocket located on an adjacent PV 2C(ATPase) in the crystal lattice. The C-terminus mediated PV 2C-2C interaction promotes self-oligomerization, most likely hexamerization, which is fundamental to the ATPase activity of 2C. The zinc finger is the most structurally diverse feature in 2C proteins. Available structural and virological data suggest that the zinc finger of 2C might confer the specificity of interaction with other proteins. We built a hexameric ring model of PV 2C(ATPase) and visualized the previously identified functional motifs and drug-resistant sites, thus providing a structure framework for antiviral drug development.

摘要： BACKGROUND Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses. METHODS We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine-derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission;the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2. RESULTS The prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (< 0.1%;95% CI, < 0.1 to 0.1) and sewage samples (8.0%;95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected countries.

摘要： The article focuses on the challenges of the organization, World Health Assembly to make policy changes post the decision to end the use of oral polio vaccines (OPV), considering the successful efforts of poliovirus eradication. Topics discussed include outbreak of circulating vaccine-derived poliovirus (cVDPV) due to wild poliovirus (WPV), role of Global Polio Eradication Initiative (GPEI), and need for research on better surveillance tools and vaccines for complete eradication of the virus.

关键词： Needle-free injection   Injectable vaccine   Polio   Supplementary vaccination activities   Vaccination campaigns  

摘要： Background: To attain high coverage during polio vaccination campaigns, an outreach house-to-house strategy is used to administer oral poliovirus vaccine. Administering an injectable vaccine house-to-house requires a skilled work force and increases risks of needle stick injuries. Needle-free injection devices provide a safer alternative to needles and syringes for administering injectable vaccines. We evaluated the feasibility and acceptability of a needle-free injection device to administer injectable poliovirus vaccine during a house-to-house vaccination outreach activity. Methods: Vaccination teams administered injectable poliovirus vaccine using the Pharmajet (R) needle-free intramuscular jet injector to children ages 6-59 months in 766 homes. Data on the feasibility of using the jet injector in an outreach campaign setting and the acceptability of the jet injector by caregivers and vaccinators were collected. Results: A total of 993 injections were administered. Vaccinators faced challenges during device preparation in 16% (n = 158) of injections;challenges were related to problems loading the injector and not having a flat surface to use for setup of the injector. Among 32 vaccinators interviewed after the vaccination campaign, the main reported advantage of the device was absence of sharps disposal (91%) while the main reported disadvantage was unacceptability by parents (90%) which was related to the vaccine, not the device. Conclusions: The needle-free jet injector was feasible for use in house-to-house campaigns. Acceptability by vaccinators was low as 81% stated that the jet injector was not easier to use than needle and syringe. Parental refusal related to frequent polio vaccination campaigns was the biggest challenge. In addition, novelty of the device posed a challenge to teams as they needed to reassure parents about safety of the device. To take full advantage of the ability to take injectable vaccines door-to-door during vaccination campaigns using

关键词： 单克隆抗体   脊髓灰质病毒Ⅰ型   Vero细胞系  

摘要： 目的:为建立脊灰病毒Sabin株Ⅰ型特异的单克隆抗体.方法:以Vero细胞增殖病毒并用蔗糖密度梯度离心法纯化后,用病毒免疫SPF级Balb/c小鼠.取小鼠免疫脾淋巴细胞与SP2/0-Ag14骨髓瘤细胞进行细胞融合,通过间接ELISA法筛选抗体阳性的杂交瘤细胞,并用有限稀释法克隆化.用细胞培养法制备脊灰病毒单抗,并以中和试验测定单抗效价.结果:获得了8株分泌抗脊灰病毒Sabin株Ⅰ型单克隆抗体的杂交瘤细胞株,其中1株G8G7能够稳定分泌抗体.间接ELISA法测得单抗的效价为1:8,中和试验测得中和抗体的效价为1:58.结论:G8G7分泌的抗体为抗脊灰病毒Sabin株Ⅰ型特异的单克隆抗体.

关键词： 脊髓灰质炎   利器   抗癌   小儿麻痹症   存期  

摘要： 胶质母细胞瘤是一种恶性程度高且生存期较短的脑癌，近日，一项新研究发现，原本会导致小儿麻痹症的脊髓灰质炎病毒，经过基因改造后却成为了对抗脑癌的利器。

关键词： 脊髓灰质炎   麻疹   疫苗   IgG抗体   免疫效果  

摘要： 目的:监测和评价永靖县1~8岁健康儿童脊髓灰质炎、麻疹疫苗免疫状况,分析上述疫苗的保护率,为实施预防接种工作提供科学依据。方法:通过酶联免疫吸附试验(ELISA)检测1~8岁健康儿童血清中脊髓灰质炎、麻疹IgG抗体,比较分析不同地区、人群疫苗保护率。结果:永靖县1~8岁儿童脊髓灰质炎和麻疹疫苗的免疫效果明显,抗体阳转率均达98%。1岁组抗体阳性率低于其他各组。结论:永靖县1~8岁健康儿童脊髓灰质炎、麻疹的抗体水平已达到85%保护率的要求,应继续加强相关疫苗免疫前后抗体水平的监测工作并严格执行免疫制度。

关键词： 脊髓灰质炎后综合征   体能   生活方式   综述  

摘要： 脊髓灰质炎后综合征患者的肌力和耐力有限,同时会新发生疲劳和无力,因此在生活中必须节省使用体能。患者可以通过调整生活方式来保存体能,需结合多学科支持来减轻症状及维持功能。患者实现保存体能需要建立使用体能的详细目录、咨询医生、评估及改善睡眠、控制体质量、空间及物品条理化、简化日常工作和家务、寻求帮助、计划休息时间、注意天气变化、识别抑郁和孤独的征象。在居家事务、烹饪、清洁、办公、户外活动中,患者要以尽可能使用保存体能的生活方式进行。

关键词： 脊髓灰质炎病毒   毕赤酵母   蔗糖密度梯度离心   病毒样颗粒  

摘要： 目的构建可稳定表达脊髓灰质炎病毒(poliovirus,PV)类病毒颗粒(virus-like particles,VLPs)的整合型重组毕赤酵母,鉴定PV VLPs在毕赤酵母细胞中的表达及组装情况。方法根据毕赤酵母密码子偏好性优化salk株II型P1和3CD基因并连接到p Pic ZA载体,构建p Pic ZA-P1-3CD表达载体;用Bgl II线性化p Pic ZA-P1-3CD载体,电转至毕赤酵母GS115中。通过Zeocin抗性筛选获得整合型重组毕赤酵母,随后用高浓度Zeocin抗性筛选得到高表达菌株。甲醇诱导后,用Western Blot检测目的蛋白表达;蔗糖密度梯度离心纯化PV VLPs并进行透射电镜观察。结果成功构建p Pic ZA-P1-3CD表达载体,获得PV VLPs重组毕赤酵母。Western Blot在重组毕赤酵母裂解上清中检测到目的蛋白的表达;蔗糖密度梯度离心纯化后,在透射电镜中观察到直径为30 nm左右的VLPs,其形态与天然的PV颗粒相似。结论成功构建PV-2型VLPs的整合型重组酵母系统,并在毕赤酵母中组装形成了VLPs,为酵母表达系统中PV VLPs疫苗的研制奠定了基础。

关键词： 急性弛缓性麻痹   非脊髓灰质炎肠道病毒   基因特征  

摘要： 目的研究2013年贵州省急性弛缓性麻痹(acute flaccid paralysis,AFP)病例中非脊髓灰质炎肠道病毒(nonpolio enterovirus,NPEV)的基因型别,并对分离的柯萨奇病毒A4型(coxsackievirus,CVA4)进行基因特征分析。方法 2013年贵州省共报告15岁以下AFP病例235例,采用RD细胞和L20B细胞对235例AFP病例粪便标本进行病毒分离,对分离到的NPEV进行VP1基因序列测定分型。通过MEGA7.0软件采用邻位相接法(neighbor joining method)构建遗传进化树进行基因特征分析,可靠性通过1 000bootstrap值评估。结果 235例AFP病例中共检测到24株NPEV(10.2%),有2株无法定型,另外22株共包括12个血清型,其中人类肠道病毒(human enterovirus,HEV)A组包括4个血清型6株,其中3株为CVA4,均属于C2基因亚型;HEV-B组包括7个血清型15株,1株为HEV-C组,未分离到HEV-D组病毒。结论 2013年贵州省AFP病例病原谱包括多种型别的NPEV,其中CVA4基因特征分析表明2013年贵州地区流行的CVA4毒株为C2基因亚型。