关键词： 急性B淋巴细胞白血病   表观遗传学   脊髓灰质炎病毒受体  

摘要： 本研究探讨急性B淋巴白血病细胞表面脊髓灰质炎病毒受体表达是否受表观遗传学调控。利用重硫酸盐PCR测序方法比较去甲基化药物5-氮杂胞苷作用前后,急性B淋巴白血病细胞系RS4:11和SUP-B15中脊髓灰质炎病毒受体基因启动子区甲基化CpG百分比的变化,利用流式细胞分析技术和实时定量PCR技术在转录和翻译水平比较该基因表达的变化;比较组蛋白去乙酰化酶抑制剂作用前后,该基因在转录和翻译水平表达的变化。结果显示:急性B淋巴白血病细胞系RS4:11和SUP-B15中脊髓灰质炎病毒受体基因启动子区存在异常高甲基化的CpG岛,经去甲基化药物作用后甲基化CpG含量减低,而且该基因在转录及蛋白水平的表达也相应增加。经过组蛋白脱乙酰酶抑制剂作用后,该基因在转录和蛋白水平的表达也相应增加。上述两种药物合用与单药作用相比,并未进一步提高该基因在转录和蛋白水平的表达,提示异常甲基化和组蛋白去乙酰化这2种表观遗传学调控机制在抑制脊髓灰质炎病毒受体表达方面没有协同作用。结论:急性B淋巴白血病细胞系表面脊髓灰质炎病毒受体表达受表观遗传学调控,药物处理后能部分逆转异常的表观遗传学调节机制,使得该基因的表达部分恢复。

关键词： 脊髓灰质炎疫苗   强化免疫   知晓率  

摘要： 目的 了解儿童家长对脊髓灰质炎疫苗强化免疫活动的知晓率以及主要知晓途径，评价预防接种知识的宣传效果。方法2011年3月～5月，在深圳市南山区采用非概率抽样方式调查适龄儿童家长，问卷调查脊髓灰质炎疫苗强化免疫活动的知晓情况。结果脊髓灰质炎疫苗强化前和强化后知晓率分别为91．9％（621／676）和97．8％（1149／1175），强化后知晓率高于强化前，常住人口知晓率和流动人口知晓率分别为97．0％（1097／1131）和93．5％（673／720），常住人群知晓率高于流动人群，差异均有统计学意义。知晓脊髓灰质炎疫苗强化免疫活动中通过宣传单、电视、医生告知的知晓比例分别占52．1％（923／1770）、32．7％（578／1770）和26．3％（466／1770）。结论开展强化免疫活动是宣传预防接种的有效方法，派发宣传单、医生告知和电视宣传是主要的宣传手段。

关键词： 脊髓灰质炎   脊髓灰质炎后综合征   继发性运动神经元病   诊断   治疗  

摘要： 1临床资料 患者,男,45岁,以＂进行性双上肢乏力2a＂为主诉入院。2a前患者出现左上肢乏力、活动失自如,不能端碗、系纽扣,后渐感右手乏力,不能持筷、不能以双手支撑起身体,伴有畏寒、畏风,语音降低并咀嚼无力,偶有饮水呛咳、肌肉痉挛,间断咳嗽,以干咳为主,少量白色稀薄痰,坐位1～2h心前区有压迫感,抬头无力,平卧位可缓解,双侧肩胛区麻木,视物清楚,无耳鸣、听力下降,无吞咽困难,无咯血。

关键词： MESSENGER RNA   OXIDATIVE stress   ENDOPLASMIC reticulum   PROTEINS   POLIOVIRUS   VIRUS diseases  

摘要： In response to environmental stress and viral infection, mammalian cells form foci containing translationally silenced mRNPs termed stress granules (SGs). As aggregates of stalled initiation complexes, SGs are defined by the presence of translation initiation machinery in addition to mRNA binding proteins. Here, we report that cells infected with poliovirus (PV) can form SGs early that contain T-cell-restricted intracellular antigen 1 (TIA1), translation initiation factors, RNA binding proteins, and mRNA. However, this response is blocked as infection progresses, and a type of pseudo-stress granule remains at late times postinfection and contains TIA but lacks translation initiation factors, mRNA binding proteins, and most polyadenylated mRNA. This result was observed using multiple stressors, including viral infection, oxidative stress, heat shock, and endoplasmic reticulum stress. Multiple proteins required for efficient viral internal ribosome entry site-dependent translation are localized to SGs under stress conditions, providing a potential rationale for the evolution and maintenance of the SG inhibition phenotype. Further, the expression of a noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells enables SGs whose constituents are consistent with the presence of stalled 48S translation preinitiation complexes to persist throughout infection. These results indicate that in poliovirus-infected cells, the functions of TIA self-aggregation and aggregation of stalled translation initiation complexes into stress granules are severed, leading to novel foci that contain TIA1 but lack other stress granule-defining components.

摘要： Cytoplasmic and endosomal RNA sensors recognize RNA virus infection and signals to protect host cells by inducing type I IFN. The cytoplasmic RNA sensors, retinoic acid inducible gene I/melanoma differentiation-associated gene 5, actually play pivotal roles in sensing virus replication. IFN-beta promoter stimulator-1 (IPS-1) is their common adaptor for IFN-inducing signaling. Toll/IL-1R homology domain-containing adaptor molecule 1 (TICAM-1), also known as TRIF, is the adaptor for TLR3 that recognizes viral dsRNA in the early endosome in dendritic cells and macrophages. Poliovirus (PV) belongs to the Picornaviridae, and melanoma differentiation-associated gene 5 reportedly detects replication of picornaviruses, leading to the induction of type I IFN. In this study, we present evidence that the TLR3/TICAM-1 pathway governs IFN induction and host protection against PV infection. Using human PVR transgenic (PVRtg) mice, as well as IPS-1(-/-) and TICAM-1(-/-) mice, we found that TICAM-1 is essential for antiviral responses that suppress PV infection. TICAM-1(-/-) mice in the PVRtg background became markedly susceptible to PV, and their survival rates were decreased compared with wild-type or IPS-1(-/-) mice. Similarly, serum and organ IFN levels were markedly reduced in TICAM-1(-/-) /PVRtg mice, particularly in the spleen and spinal cord. The sources of type I IFN were CD8 alpha(+)/CD11c(+) splenic dendritic cells and macrophages, where the TICAM-1 pathway was more crucial for PV-derived IFN induction than was the IPS-1 pathway in ex vivo and in vitro analyses. These data indicate that the TLR3/TICAM-1 pathway functions are dominant in host protection and innate immune responses against PV infection. The Journal of Immunology, 2011, 187: 5320-5327.

关键词： 急性弛缓性瘫痪   周围神经功能   手足口病   非脊髓灰质炎肠道病毒   患儿   检测   下肢   肢体功能障碍  

摘要： 手足口病（hand-foot-mouth disease）是非脊髓灰质炎肠道病毒引起的常见传染病,常可引起神经损伤。主要累及脑和脊髓,周围神经较少受累,但可遗留持久肢体功能障碍,可单独或与脑损伤同时存在。关于手足口病合并急性弛缓性瘫痪的患儿，偶见报道且多为个案或临床症状分析[1-5]，常为磁共振成像提示脊髓节段性或前角细胞损害，

关键词： Mucosal immunity   Poliomyelitis   Poliovirus   Disease eradication  

摘要： Since the resolution of the World Assembly in 1988 to eradicate polio globally, substantial progress toward this target has been achieved, but the final goal remains elusive. India and other tropical developing countries present a unique challenge because of the much lower oral poliovirus vaccine (OPV) immunogenicity compared to industrialized countries, both in terms of humoral and mucosal immunity. To overcome this challenge, further research is needed to elucidate the causes for the suboptimal OPV immunogenicity, better defining the optimal vaccine schedules and delivery strategies, developing and evaluating adjuvants to boost OPV immunogenicity, and improving the methods for directly measuring mucosal immunity. (C) 2011 World Health Organization.. Published by Elsevier Ltd. All rights reserved.

关键词： Poliovirus 2A   Alternative splicing   Viral proteases   Spliceosome  

摘要： Viruses have developed multiple strategies to interfere with the gene expression of host cells at different stages to ensure their own survival. Here we report a new role for poliovirus 2A(pro) modulating the alternative splicing of pre-mRNAs. Expression of 2A(pro) potently inhibits splicing of reporter genes in HeLa cells. Low amounts of 2A(pro) abrogate Fas exon 6 skipping, whereas higher levels of protease fully abolish Fas and FGFR2 splicing. In vitro splicing of MINX mRNA using nuclear extracts is also strongly inhibited by 2A(pro), leading to accumulation of the first exon and the lariat product containing the unspliced second exon. These findings reveal that the mechanism of action of 2A(pro) on splicing is to selectively block the second catalytic step. (C) 2011 Elsevier Inc. All rights reserved.

关键词： Animals   Cell Line, Tumor   Cricetinae   Cysteine Endopeptidases/metabolism   Eukaryotic Initiation Factor-2/metabolism   Eukaryotic Initiation Factor-4G/metabolism   Humans   Poliovirus/enzymology   Poliovirus/genetics   Protein Biosynthesis   Proteolysis   RNA, Messenger/genetics   RNA, Messenger/metabolism   RNA, Viral/genetics   RNA, Viral/metabolism   Viral Nonstructural Proteins/metabolism   Viral Proteins/metabolism  

摘要： Poliovirus RNA utilizes eIF2 for the initiation of translation in cell free systems. Remarkably, we now describe that poliovirus translation takes place at late times of infection when eIF2 is inactivated by phosphorylation. By contrast, translation directed by poliovirus RNA is blocked when eIF2 is inactivated at earlier times. Thus, poliovirus RNA translation exhibits a dual mechanism for the initiation of protein synthesis as regards to the requirement for eIF2. Analysis of individual poliovirus non-structural proteins indicates that the presence of 2A(pro) alone is sufficient to provide eIF2 independence for IRES-driven translation. This effect is not observed with a 2A(pro) variant unable to cleave eIF4G. The level of 2A(pro) synthesized in culture cells is crucial for obtaining eIF2 independence. Expression of the N-or C-terminus fragments of eIF4G did not stimulate IRES-driven translation, nor provide eIF2 independence, consistent with the idea that the presence of 2A(pro) at high concentrations is necessary. The finding that 2A(pro) provides eIF2-independent translation opens a new and unsuspected area of research in the field of picornavirus protein synthesis.

关键词： LETTERS to the editor   POLIO  

摘要： A letter to the editor is presented in response to an article about a case of vaccine-derived poliomyelitis, by DeVries and colleagues published in the June 16, 2011 issue.