关键词： 脊髓灰质炎病毒   追踪   艾滋病毒   SARS病毒   禽流感病毒   埃博拉病毒   人类健康   乙肝病毒  

摘要： 在地球上，对人类健康威胁最大的病毒是什么？你的脑中，或许马上会闪现出艾滋病毒、禽流感病毒、SARS病毒、脊髓灰质炎病毒、埃博拉病毒、马尔堡病毒等各种答案。但实际上，正确答案，却是乙肝病毒。

摘要： We have applied Hierarchical QSAR Technology (HiT QSAR) approach employing simplex representation of molecular structure to the analysis of in vitro inhibitory effects of dual combinations of picornavirus replication inhibitors against poliovirus 1 (Mahoney). The possible dual combinations of arildone, disoxaril, enviroxime, guanidine, HBB, PTU-23, ribavirin and S-7 were investigated. Antiviral activity was expressed in lgIC50 (μM). Both molecules in the binary combinations were represented their simplexes. These representation allowed analyzing the synergy, antagonism or additivity in the combination's interaction with the biological target. We dubbed this approach as “double 2D QSAR”. Predictive QSAR models were obtained using PLS approach and validated using 8- fold external cross-validation (R2 ext = 0.67-0.93). Adequate models (R2 ext = 0.53-0.97) were obtained in the same way for IC30, IC40, IC60 and IC70 inhibitory concentrations. The usage of predicted values of IC30, IC40, IC60 and IC70 in the framework of the feature net approach allowed to increase the quality of our QSAR model (R2 ext = 0.71-0.94). Resulting QSAR models were analyzed, structural fragments and parts of combination promoting the antiviral activity were determined, e.g. oxypropylisoxasole. The developed model was then used to predict novel potent combinations of drugs. Oxoglaucine and pleconaril (which was very similar to disoxaril) were predicted as novel potent components of an inhibitory combination. HiT QSAR proved itself as an adequate tool for QSAR analysis of combinations and, although the method used is suitable only to binary combinations, it can be easily extended for more complex tasks.

关键词： chimpanzees   great apes   neutralizing antibodies   poliomyelitis   transmission  

摘要： Background To understand immunological responses in chimpanzees vaccinated with live-attenuated vaccine (oral polio vaccine;OPV), serum neutralizing antibodies against poliovirus types 1, 2, and 3 were investigated over time. Methods The neutralizing antibody titers against poliovirus types 1, 2, and 3 were determined by microneutralization test using 100 ID(50) of poliovirus types 1, 2, and 3 (Sabin strains). Results Neutralizing antibodies against poliovirus types 1, 2, and 3 were detected in 85.7%, 71.4%, and 65% of the serum from 42 chimpanzees tested 9 years post-vaccination. The neutralizing antibody titers in chimpanzees were similar to the documented levels in human studies as an indicator of vaccine efficacy. Conclusions This study reveals persistence of neutralizing antibodies in chimpanzees for at least 9 years after vaccination with OPV. This first study in chimpanzees provides useful information for the evaluation of the success of vaccination with OPV in other captive apes.

关键词： OPV-derivatives   RCT test   One-step growth curve experiment  

摘要： Attenuated strains of Sabin poliovirus vaccine replicate in the human gut and in rare cases may cause vaccine-associated paralytic poliomyelitis (VAPP). Mutations at specific sites of the genome and recombination between Sabin strains may result in the loss of the attenuated phenotype of OPV (Oral Poliovirus Vaccine) strains and the acquisition of traits characteristic of wild polioviruses, such as increased neurovirulence and loss of temperature sensitivity. In this study, we determined the phenotypic traits such as temperature sensitivity and growth kinetics of eight OPV isolates (six bi-recombinant and two non-recombinant). The growth phenotype of each isolate as well as of Sabin vaccine strains in Hep2 cell line at two different temperatures (37 and 40A degrees C) was evaluated using two different assays, RCT test (Reproductive Capacity at different Temperatures) and one-step growth curve analysis. Moreover, the nucleotide and amino acid positions in the genomes of the isolates that have been identified as being involved in the attenuated and thermo sensitive phenotype of Sabin vaccine strains were investigated. Mutations that result in loss of the attenuated and thermo sensitive phenotype of Sabin vaccine strains were identified in the genomes of all isolates. Both mutations and recombination events correlated well with the reverted phenotypic traits of OPV-derivatives. In the post-eradication era of wild polioviruses, the identification and the characterization (genomic and phenotypic) of vaccine-derived polioviruses become increasingly important in order to prevent cases or even outbreaks of paralytic poliomyelitis caused by neurovirulent strains.

摘要： V-073, an enterovirus capsid inhibitor, has potent broad spectrum of anti-poliovirus activity in vitro. The compound has exhibited desirable attributes in nonclinical pharmacologic and toxicologic studies, which support the continued advancement of V-073 to first-in-human clinical studies. These attributes will be reviewed, as will the rationale for additional poliovirus antiviral development.

关键词： PVS-RIPO   Glioblastoma multiforme   Central nervous system  

摘要： PVS-RIPO is a genetically recombinant, non-pathogenic poliovirus chimera with a tumor-specific conditional replication phenotype. Consisting of the genome of the live attenuated poliovirus type 1 (Sabin) vaccine with its cognate IRES element replaced with that of human rhinovirus type 2. PVS-RIPO displays an inability to translate its genome in untransformed neuronal cells, but effectively does so in cells originating from primary tumors in the central nervous system or other cancers. Hence, PVS-RIPO unleashes potent cytotoxic effects on infected cancer cells and produces sustained anti-tumoral responses in animal tumor models. PVS-RIPO presents a novel approach to the treatment of patients with glioblastoma multiforme, based on conditions favoring an unconventional viral translation initiation mechanism in cancerous cells. In this review we summarize advances in the understanding of major molecular determinants of PVS-RIPO oncolytic efficacy and safety and discuss their implications for upcoming clinical investigations. (C) 2010 Elsevier Ltd. All rights reserved.

关键词： 贝类   果蔬   水样   脊髓灰质炎病毒   检测   RT-PCR方法   荧光RT-PCR方法   水产品   水产养殖  

标准号: SN/T 2530-2010

摘要： 本标准规定了贝类、果蔬和水样中脊髓灰质炎病毒普通RT-PCR方法和实时荧光RT-PCR方法。本标准适用于贝类、果蔬和水样中脊髓灰质炎病毒的定性检测。

关键词： 口服脊髓灰质炎减毒活疫苗   效价   检测  

摘要： 目的了解甘肃省口服脊髓灰质炎（脊灰）减毒活疫苗（OPV）的质量（效价）变化情况。方法按省、市、县、乡四级逐级抽样北京天坛生物制品有限公司生产的脊灰减毒活疫苗，用脊灰效价微量细胞培养法进行检测。结果2003～2005年OPV检测除2004年古浪县疾控中心外，其余均达到≥3．50Log CCID50／ml人群免疫有效标准。结论脊灰疫苗效价检测是有效免疫的重要保证。

关键词： 脊髓灰质炎疫苗   强化免疫  

摘要： 自1988年以来，全球消灭脊髓灰质炎行动使全球脊髓灰质炎发病率减少了99％以上。目前，消灭脊髓灰质炎工作遇到了新问题。世界卫生组织（WHO）分忻了当前遇到的困难，制定了消灭脊髓灰质炎工作的目标及实施策略。