关键词： RNA   replication   DNA-Directed RNA Polymerase   Proteins   Polioviruses  

摘要： We have previously described the RNA replication properties of poliovirus transcripts harboring chimeric RNA polymerase sequences representing suballelic exchanges between poliovirus type 1 (PV1) and coxsackievirus B3 (CVB3) utilizing an in vitro translation and RNA replication assay (C. Cornell, R. Perera, J. E. Brunner, and B. L. Semler, J. Virol. 78:4397-4407, 2004). We showed that three of the seven chimeras were capable of RNA replication in vitro, although replication levels were greatly reduced compared to that of wild-type transcripts. Interestingly, one of the replication-competent transcripts displayed a strand-specific RNA synthesis defect suggesting (i) a differential replication complex assembly mechanism involving 3D and/or precursor molecules (i.e., 3CD) required for negative- versus positive-strand RNA synthesis or (ii) effect(s) on the ability of the 3D polymerase to form higher-ordered structures required for positive-strand RNA synthesis. In this study, we have attempted to rescue defective RNA replication in vitro by cotranslating nonstructural proteins from a transcript encoding a large precursor polyprotein (P3) to complement 3D polymerase and/or precursor polypeptide functions altered in each of the chimeric constructs. Utilization of a wild-type P3 construct revealed that all transcripts containing chimeric PV1/CVB3 polymerase sequences can be complemented in trans for both negative- and positive-strand RNA synthesis. Furthermore, data from experiments utilizing genetically modified forms of the P3 polyprotein, containing mutations within 3C or 3D sequences, strongly suggest the existence of different protein-protein and protein-RNA interactions required for positive- versus negative-strand RNA synthesis. These results, combined with data from in vitro RNA elongation assays, indicate that the delivery of active 3D RNA polymerase to replication complexes requires a series of macromolecular interactions that rely on the presence of specific 3D

关键词： allogeneic SCT   poliovirus   immunity   long term  

摘要： Revaccination with poliovirus after allogeneic stem cell transplant (SCT) is usually effective, but the longevity of this immunity is unknown. Therefore, poliovirus immunity was studied in 134 patients having survived at least 5 years after vaccination. The median follow-up from vaccination was 8 years (1-19 years). In all, 21 (15.6%) patients had become seronegative to at least one of the poliovirus serotypes during follow-up. The estimated probabilities of remaining immune to poliovirus at 5 and 10 years after vaccination were 94 and 94% for subtype 1, 98 and 94% for subtype 2, and 93 and 90% for subtype 3, respectively. In multivariate analysis, the only risk factor for loss of immunity was younger patient age (P<0.01), and there was a strong trend for patients with chronic GVHD to lose immunity more rapidly (P=0.07). A total of 14 patients received a booster dose of an inactivated poliovirus vaccine and all responded. We conclude that poliovirus immunity is retained long term after revaccination in most patients after allogeneic SCT.

关键词： Humans   Immunity   Herd   Poliomyelitis   Poliovirus   Poliovirus Vaccine   Oral  

摘要： The second reason is more important. Vaccine viruses are genetic mutants of wild virus strains, with greatly reduced neurovirulence and transmissibility. Neurovirulence can increase as a result of back-mutations, occurring during replication and transmission. As such, oral polio vaccine can give rise to rare sporadic vaccine-associated paralytic polio (VAPP) in vaccinated children or in unvaccinated contacts.

关键词： Placebos   Infant formula   Polioviruses  

摘要： To determine whether the size of the intestinal bifidobacterial population can influence the immune response to poliovirus vaccination in infants, we set up a randomized, placebo-controlled trial. From birth to 4 mo, infants were given a fermented infant formula (FIF) or a standard formula (placebo). Bifidobacteria were quantified monthly in infant stools. Antipoliovirus IgA response to Pentacoq(R) was assessed before and 1 mo after the second vaccine injection. Thirty infants were randomized, and 20 completed the study (nine in the placebo group and 11 in the FIF group). Fecal bifidobacterial level was significantly higher with the FIF group at 4 mo of age (p = 0.0498). Furthermore, B. longum/B. infantis carriage was higher at 4 mo in the FIF group (p = 0.0399). Antipoliovirus IgA titers increased after Pentacoq(R) challenge (p < 0.001), and the rise was significantly higher in the FIF group (p < 0.02). Antibody titers correlated with bifidobacteria, especially with B. longum/B. infantis and B. breve levels (p < 0.002). Infants who harbored B. longum/B. infantis also exhibited higher levels of antipoliovirus IgAs (p < 0.002). In conclusion, the present results indicate that antipoliovirus response can be triggered with a fermented formula that is able to favor intestinal bifidobacteria. Whether this effect on the immune system is achieved through the bifidogenic effect of the formula (mainly through B. longum/B. infantis and B. breve stimulation) or directly linked to compounds (i.e. peptides) produced by milk fermentation remains to be investigated.

关键词： multiple sclerosis   genetics   virus entry receptors   polio-virus receptor   herpesvirus mediator entry B   ApoE4  

摘要： Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS). Although the cause of MS is still uncertain, it is well accepted that both genetic and environmental factors are important for the development of disease. In this study, we focused on the Polio Virus Receptor (PVR) and Herpesvirus entry mediator B (HVEB) receptor genes, which are located on chromosome 19q13, a region previously linked to MS. Both receptors are expressed in the brain and immune system and play an important role for inter-cellular adhesion and entry of neurotropic viruses to the brain. We identified four new polymorphisms in the PVR gene, which were located in the promoter region and three different exons. All exonic polymorphisms altered the amino acid sequence of the receptor. No new polymorphisms were found in the HVEB gene, but we confirmed a previously identified intronic polymorphism. We analyzed the frequency of the polymorphisms by RFLP analysis in sporadic MS patients, MS families, and healthy controls and determined the surface expression of HVEB and PVR on peripheral blood monocytes. We did not find differences in the frequency of the polymorphisms or surface expression between MS patients and controls. Overall, our findings do not support a role of HVEB and PVR genes in the development of MS. (C) 2004 Elsevier B.V. All rights reserved.

关键词： poliovirus   mutant   vaccine   thermostability   Sabin strain  

摘要： Poliovirus is heat-labile;on heating at 50degreesC for 30 min its infectivity decreases drastically and its antigenicity reverts from N to H. However, mutants resistant to heating at 50degreesC for 30 min from the Sabin 1 and 2 viruses were isolated by repeating the process of incubation of the virus stock at 50degreesC for 30 min and multiplication of the remaining virus in a cell culture. The isolated mutants were stable genetically, and maintained the rct and d markers of the parent virus. On electron microscopical examination, the mutants were observed to retain the intact morphology after being heated at 50degreesC for 30 min, while the parent virus was converted to empty particles devoid of RNA under the same conditions. On determination of the nucleotide sequence of the P1 region, a single nucleotide sequence substitution was detected at nucleotide no. 2741, resulting in an amino acid change from valine to alanine at the 87th position of VP1. This amino acid might be associated with the heat-resistance of the mutants. Furthermore, it was found that the thermostable mutants obtained in this study, which are resistant to "high" temperature (50degreesC) for a short time (30 min), were not stable against heating at the ambient temperature (37degreesC) for a long time (5 or 7 days). This suggests that the inactivation at high temperature for a short time and that at ambient temperature for a long time involve different mechanisms. (C) 2004 Wiley-Liss, Inc.

关键词： POLIOVIRUS   VIRAL vaccines   TRANSGENIC mice   IMMUNE response   SERUM   SALIVA  

摘要： An assay for the evaluation of protective properties of inactivated poliovirus vaccines (IPVs) in transgenic (Tg) mice susceptible to poliovirus has been developed and optimized for type 2 IPV. This method was used to compare the immunogenicity and protective properties of experimental IPV produced from the attenuated Sabin strain (sIPV) with those of conventional IPV (cIPV) produced from the wild-type (wt) poliovirus MEF-1 strain. Modified enzyme-linked immunosorbent assays (ELISAs) were used to measure immune response in serum and saliva samples from test mice. Tg mice were vaccinated and were challenged either with wt poliovirus or virulent poliovirus derived from the vaccine strain. Compared with cIPV, sIPV induced lower levels of antibodies and did not completely protect mice against challenge with wt virus but did protect mice against challenge with the virulent vaccine-derived strain. This may be due to an 18% nucleotide difference between the MEF-1 and Sabin 2 strains, resulting in 72 amino acid substitutions and leading to antigenic dissimilarity. Immunological properties of both strains, revealed by cross-neutralization tests and ELISAs, confirmed that MEF-1 possesses broader immunogenicity than does Sabin 2. This animal model may be used for the assessment of new IPVs and of combination vaccines containing an IPV component.

关键词： 脊髓灰质炎病毒   脊髓灰质炎疫苗   循环   爆发  

摘要： 本文介绍了脊髓灰质炎疫苗衍生病毒 (VDPV)循环和引起脊髓灰质炎爆发的情况 ,循环 VDPV(c VDPV)出现和传播的危险因素 ,c VDPV分离株的特性及实验室监测 ,c VDPV对全球消灭脊髓灰质炎策略的影响。

关键词： BRAIN tumors   GASTROINTESTINAL system   POLIOVIRUS   ONCOLOGY  

摘要： Body. Previous reports have indicated that oncolytic polioviruses may be useful in the treatment of malignant brain tumors. We sought to determine whether gastrointestinal cancers are also potential targets of oncolytic polioviruses. Methods. In vitro analysis of the growth characteristics of wild-type poliovirus, PVM, and three attenuated mutant poliovirus chimeras in established human gastrointestinal cancer cell lines were performed. Results. The poliovirus chimera RIPO and its derivatives have the capacity to establish productive infection comparable to the wild-type poliovirus, in multiple colon cancer cell lines (RKO, SW480, LoVo), AGS gastric cancer, and Mia PaCa pancreas cancer cell lines. The growths in these cell lines are nearly identical when compared to their growth in standard HeLa cells. Growth in two additional pancreas cancer cell lines, Panc-1 and BxPC-3, was suboptimal. Conclusions. We have determined that the poliovirus chimera RIPO establishes productive infections in a variety of gastrointestinal malignancies, indicating that gastrointestinal malignancies are a potential target for oncolysis by attenuated chimeric polioviruses like RIPO. We plan to begin studies in animal models to determine whether RIPO viruses may be an effective treatment for metastatic gastrointestinal cancers. Download : Download full-size image

关键词： 强化免疫活动   接种率   脊髓灰质炎疫苗   接种对象   快速评估   调查   效果分析   广东省  

摘要： 目的　了解广东省 2 0 0 3～ 2 0 0 4年脊髓灰质炎 (脊灰 )疫苗强化免疫活动效果。方法　按强化免疫活动实施方案于 2 0 0 3年 12月 5～ 6日和 2 0 0 4年 1月 5～ 6日在广东省全省范围开展脊灰疫苗强化免疫活动 ,逐级进行资料汇总上报 ,并采用随机原则进行现场快速评估。结果　全省各地上报第一轮应接种对象 2 70 10 2 9人 ,已接种 2 6 2 5 0 39人 ,接种率为 97 2 % ;第二轮应接种对象 2 76 974 5人 ,已接种 2 6 935 4 5人 ,接种率为 97 2 %。现场快速评估 ,第一轮共调查 794 7名对象 ,接种率为97 1% ,上卡率为 92 9% ;第二轮共调查 75 39名对象 ,接种率为 98 2 % ,上卡率为 94 1%。结论　两轮强化免疫活动的脊髓灰质炎疫苗接种率均达到 95 %以上的目标。今后应继续加强对流动儿童的免疫接种工作。