关键词： Antibodies, Viral/blood   Double-Blind Method   Feces/virology   Humans   Infant   Infant, Newborn   Male   Poliomyelitis/prevention & control   Poliomyelitis/prevention & control   Poliovirus/immunology   Poliovirus/isolation & purification   Poliovirus Vaccine, Oral/adverse effects   Poliovirus Vaccine, Oral/immunology   Vaccination  

摘要： Background Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV). Methods We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429. Results 900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 wa

关键词： Poliomyelitis   Vaccines   Developing countries--LDCs   Conflicts of interest  

摘要： Highly divergent immune and anonymous vaccine-derived polioviruses may be bigger bumps in the road to polio eradication than circulating vaccine-derived polioviruses (cVDPVs).1 The definition of "vaccine-derived polioviruses" is artificial, since some isolates from cVDPV outbreaks2 diverged by less than 1%, whereas immune and anonymous vaccine-derived polioviruses have by now diverged by more than 15%.34 Minimal amino acid changes in cVDPV neutralizing antigenic sites permit rapid control through OPV immunization campaigns.12 In contrast, immune vaccine-derived poliovirus infections have not been cured,5 and the number of anonymous persistent secretors is unknown.4 Antibody titers against neurovirulent immune vaccine-derived polioviruses were reduced by numerous amino acid substitutions in their neutralizing antigenic sites, and in a highly immune population (with >95% coverage), 7% of adults had titers of less than 1:8 against one or more type 2, anonymous vaccine-derived poliovirus isolates.4 Immune and anonymous vaccine-derived polioviruses are potential sources for the reemergence and rapid spread of poliomyelitis when population immunity will decrease through underimmunization,2 concerted global cessation of OPV vaccination, or waning immunity in individual persons.

关键词： eIF4G   IRES   poliovirus   polypyrmidine tract-binding protein (PTB)   tethered hydroxyl-radical probing  

摘要： Tethered hydroxyl-radical probing has been used to determine the orientation of binding of polypyrimidine tract-binding protein (PTB) to the poliovirus type 1 (Mahoney) (PV-1(M)) internal ribosome entry site/segment (IRES)-the question of which RNA-binding domain (RBD) binds to which sites on the IRES. The results show that under conditions in which PTB strongly stimulates IRES activity, a single PTB is binding to the IRES, a finding which was confirmed by mass spectrometry of PTB/IRES complexes. RBDs1 and 2 interact with the basal part of the Domain V irregular stem loop, very close to the binding site of eIF4G, and RBDs3 and 4 interact with the single-stranded regions flanking Domain V. The binding of PTB is subtly altered in the presence of the central domain (p50) of eIF4G, and p50 binding is likewise modified if PTB is present. This suggests that PTB stimulates PV-1(M) IRES activity by inducing eIF4G to bind in the optimal position and orientation to promote internal ribosome entry, which, in PV-1(M), is at an AUG triplet 30 nt downstream of the base of Domain V. The EMBO Journal (2010) 29, 3710-3722. doi:10.1038/emboj.2010.231;Published online 21 September 2010

关键词： Catalysis   Ligands   Magnetic Resonance Spectroscopy   Methionine/chemistry   Mutation, Missense   Nucleotides/metabolism   Poliovirus/enzymology   Protein Binding   Protein Conformation   RNA Replicase/chemistry   RNA Replicase/genetics   RNA Replicase/metabolism  

摘要： The fidelity of the poliovirus RNA-dependent RNA polymerase (3D(pol)) plays a direct role in the genomic evolution and pathogenesis of the virus. A single site mutation (Gly64Ser) that is remote from the catalytic center results in a higher fidelity polymerase. NMR studies with [methyl-C-13]methionine-labeled protein were used to compare the solution structure and dynamics of wild-type and Gly64Ser 3D(pol). The chemical shifts for the Met6 resonance were significantly different between wild-type and Gly64Ser 3D(pol) when bound in ternary complexes with RNA and incorrect, but not with correct, nucleotide, suggesting that the Gly64Ser mutation induces structural changes in the N-terminal beta-strand when the enzyme is bound to incorrect but not correct nucleotide. We also observe changes in the transverse relaxation times for methionines near regions important for nucleotide and RNA binding and catalysis. Our strategy to assign the [methyl-C-13]methionine resonances involved separately mutating each of the 17 methionines. Several substitutions produced additional resonances for both Met6 and Met187, a reporter for RNA binding, and conformational changes in the highly conserved motif B loop, even though these methionines are greater than 20 A apart. The results for Gly64Ser and the other mutants are intriguing considering that they can result in structural and/or dynamic changes to methionines distant from the site of mutation. We propose that there is a long-distance network operating throughout 3D(pol) that coordinates ligand binding, conformational changes, and catalysis. Mutation of Gly64 results in structural and/or dynamic changes to the network that may affect polymerase fidelity.

关键词： 副黏病毒Tianjin株   缺损性干扰颗粒   脊髓灰质炎病毒   免疫应答  

摘要： 目的 探讨副黏病毒Tianjin株缺损性干扰（DI）颗粒作为新型生物佐剂的可行性.方法 分离提纯副黏病毒Tianjin株DI颗粒并鉴定,和脊髓灰质炎病毒（PV）灭活抗原等量混合后给小鼠皮下多点注射,并设氢氧化铝凝胶佐剂组、无佐剂组以及空白对照组.于免疫后14 d摘眼球取血检测免疫血清PV特异性IgG 无菌取脾脏制备脾细胞悬液,分别用MTT法进行T、B淋巴细胞增殖试验以及检测脾淋巴细胞接受PV灭活抗原再次刺激后IFN-γ、IL-4的产生情况.结果 副黏病毒Tianjin株DI颗粒佐剂组T、B淋巴细胞刺激指数（SI）、脾淋巴细胞分泌IFN-γ的量与其他组相比较,差异有统计学意义（P＜0.05）.结论 副黏病毒Tianjin株DI颗粒具有一定的增强机体免疫应答能力的作用,且以诱导Th1型细胞免疫应答为主.

关键词： 预防   小儿麻痹症   中风   产后脱发   脊髓灰质炎减毒活疫苗   高血压病   脑血栓   免疫作用   热线   头发  

摘要： 康姐欢迎您将烦恼告诉她本栏目将针对读者提出的有关健康的问题,请相关医生和专家解答,并在本栏目刊出,以此方式达到编者与读者互动的目的,更好地为读者服务。康姐欢迎您将身边遇到的健康问题告诉她!"康姐热线"电话:64407353E-mail:health2008@sohu.

关键词： 无脊髓灰质炎状态   2009年   上海市   监测工作   急性弛缓性麻痹   脊髓灰质炎疫苗   无脊灰状态   病例监测  

摘要： 上海市自1988年起已连续22年无脊灰野病毒病例发生,根据卫生部(2003-2010年全国保持无脊髓灰质炎状态行动计划》要求,2009年维持无脊灰状态仍是本市免疫规划的工作重点,在加强急性弛缓性麻痹(AFP)病例监测的基础上,保持高水平的脊髓灰质炎疫苗(OPV)的接种率,建立有效的免疫屏障。现将2009年上海市维持无脊灰状态的工作进展分析如下。[第一段]

关键词： CANCER treatment   POLIOVIRUS   GLIOBLASTOMA multiforme   MITOGEN-activated protein kinases   PHOSPHORYLATION   PHOSPHOINOSITIDES   THERAPEUTIC use  

摘要： Many animal viruses exhibit proficient growth in transformed cells, a property that has been harnessed for the development of novel therapies against cancer. Despite overwhelming evidence for this phenomenon, understanding of the molecular mechanisms enabling tumor-cell killing is rudimentary for most viruses. We report here that growth and cytotoxicity of the prototype oncolytic poliovirus (PV), PVSRIPO, in glioblastoma multiforme (GBM) is promoted by mitogen-activated protein kinases (MAPKs) converging on the MAPK signal-integrating kinase 1 (Mnk1) and its primary substrate, the eukaryotic initiation factor (eIF) 4E. Inducing Mnk1-catalyzed eIF4E phosphorylation through expression of oncogenic Ras substantially enhanced PVSRIPO translation, replication, and cytotoxicity in resistant cells. This effect was mimicked by expression of constitutively active forms of Mnk1 and correlated with enhanced translation of subgenomic reporter RNAs. Our findings implicate Mnk1 activity in stimulation of PVSRIPO cap-independent translation, an effect that can be synergistically enhanced by inhibition of the phosphoinositide-3 kinase (PI3K).

摘要： Polioviruses, as with all RNA viruses, are in a constant process of evolution driven by different mechanisms. With multiple mechanisms for genetic variability, they are successful conformists, adapting to changes in their habitat. The evolution of polioviruses may occur with generation of point mutations followed by genetic drift and selection. The mutation rate of polioviruses based on several studies is approximately 3 x 10(-2) mutations/synonymous site/year in the gene encoding viral protein 1. Genetic variation in polioviruses may also be increased by sharing of genetic data of two different poliovirus lineages by means of homologous recombination. According to the current view, recombination is considered usually to occur by strand-switching, but a non-replicative model has also been described. In recombination, polioviruses may either gain a set of advantageous mutations selected and fixed in previous generations of the parental viruses or get rid of deleterious ones. The prerequisites and constraints of the evolution mechanisms will be discussed. Furthermore, consequences of poliovirus evolution will be reviewed in the light of observations made on currently circulating polioviruses. We will also describe how polioviruses strike back: as wild type polioviruses approach eradication, vaccine derived strains increase their occurrence and genetic variability. Copyright (C) 2010 John Wiley & Sons, Ltd.

关键词： Greece   immunity   OPV derivatives   Polioviruses  

摘要： P>In this study, the serological status of the southern Greek population in the 1-10-year, 11-20-year, 21-30-year and 31-40 -year age groups with regard to Sabin vaccine strains and a collection of 15 recombinant and four non-recombinant poliovirus vaccine strains was determined. For all three poliovirus types, the highest neutralization test (NT) titres were observed in the 1-10-year age group, indicating a good response to vaccination. In general, the serological status of the population of southern Greece with regard to poliovirus is better for types 1 and 2 than for type 3. The presence of the lowest NT titre in the 21-30-year age group against poliovirus type 3 suggests the need for a booster dose of monovalent Sabin3 vaccine to ensure personal and herd immunity.