关键词： 脊灰野病毒   口服脊髓灰质炎疫苗   免疫接种率   调查   尼日尔   病例监测   脊灰疫苗   停止   尼日利亚   西非  

摘要： 在西非,消灭脊髓灰质炎(脊灰)的努力取得了巨大进展.通过急性弛缓性麻痹(AFP)病例监测的实施和口服脊灰疫苗(OPV)的应用,脊灰野病毒的传播已经几乎在所有的非洲国家停止.

关键词： 5′端非编码区   滴度   二倍体细胞   脊髓灰质炎病毒   人胚   序列变异   感染性   代次   传代   位点  

摘要： 目的　探索Sabin 1型脊髓灰质炎病毒在人胚肺二倍体细胞适应过程中 5′端非编码区序列变异及其与病毒感染性滴度的关系。方法　将Sabin 1型脊髓灰质炎病毒疫苗株在人胚肺二倍体细胞KMB17中连续传 11代 ,检测连续传代后感染性滴度 ,并检测 11个代次 5′端非编码区序列。结果　随着传代次数的增加 ,感染性滴度逐渐升高 ,在第 7代达到最高 ,为8 12 5LgTCID50 ml。在传代过程中 ,从第 3代起 5′端非编码区 74 2个核苷酸只出现 1个位点发生变异 ,第 6 39位由A变为G。结论　Sabin 1型脊髓灰质炎病毒经KMB17细胞传 11代 ,已适应KMB17细胞。Poliovirus 5′端非编码区与毒力直接相关的第4 80位核苷酸未发生回复突变。

关键词： Sabin2型脊髓灰质炎病毒   感染性滴度   5′端非编码区   人胚肺二倍体细胞   适应性传代培养   变异  

摘要： To investigate the adaptation of poliovirus Sabin 2 in human embryonic lung diploid fibroblast（KMB17） and its relation to nucleotide mutations of 5′ noncoding region（5′NCR）,the Sabin 2 vaccine virus was passaged serially in KMB17 for seventeen *** infectious titers of Sabin 2 virus increased along with the passages,the highest titer reached 8.0 LgCCID50/ml at passage 13（P13）.During passage,there were three nucleotide mutations appeared in 5′NCR,G changed to C at position 20,C to U at position 189 and G to A at position *** results showed that Sabin 2 poliovirus adapted well in KMB17 after 17 *** nucleotide mutation at position 481 that appeared from passage 3 on indicated the possibility of virulent reversion.

关键词： error catastrophe   lethal mutagenesis   quasispecies   ribavirin   RNA-dependent RNA polymerase   RdRp fidelity  

摘要： Positive strand RNA virus populations are a collection of similar but genetically different viruses. They exist as viral quasispecies due to the high mutation rates of the low fidelity viral RNA-dependent RNA polymerase (RdRp). It is thought that this genomic heterogeneity is advantageous to the population, allowing for adaptation to rapidly changing environments that present varying types and degrees of selective pressure. However, one consequence of this extensive diversity is the susceptibility to mutagens that further increase sequence variation. Since RNA viruses live at the edge of maximal variability, an increase in the mutation rate is likely to force the virus beyond the tolerable mutation frequency into 'error catastrophe'. One such mutagen, ribavirin, is an antiviral nucleoside analog that is mutagenic to several RNA viruses. Ribavirin is incorporated into the viral genome causing lethal mutagenesis and a subsequent decrease in the specific infectivity. Even so, passaging poliovirus in the presence of low to intermediate concentrations of the drug leads to the emergence of a viral population resistant to the effects of ribavirin. These viruses have a point mutation in the RdRp that increases the overall polymerase fidelity. Interestingly, as predicted by the quasispecies theory, ribavirin resistant viruses are less adaptable, as they are more susceptible to other non-mutagenic antiviral drugs and are highly attenuated in vivo. Here, we review the mechanism of action of ribavirin on poliovirus and other RNA viruses, the possibility for escape via increased fidelity of the viral polymerase, the consequences of this response on viral population dynamics, and the biological implications for the therapeutic use of mutagenic antiviral agents. (C) 2004 Elsevier B.V. All rights reserved.

关键词： Adolescent   Adult   Age Distribution   Aged   Antibodies   Viral   Australia   Chi-Square Distribution   Child   Child   Preschool   Comparative Study   Confidence Intervals   Female   Humans   Immunity   Active   Male   Middle Aged   Neutralization Tests   Poliomyelitis   control   Poliovirus   Poliovirus Vaccine   Inactivated   Population Surveillance   Probability   Research Support   Non-U.S. Gov't   Seroepidemiologic Studies   Sex Distribution   Vaccination   numerical data  

摘要： Objective: To measure immunity to poliovirus types 1, 2 and 3 in the Australian population. Methods: Sera were collected opportunistically from laboratories around Australia between 1996 and 1999. A representative sample by age and gender was tested for neutralising antibodies to poliovirus types 1, 2 and 3. A titre of greater than or equal to8 was considered antibody positive and indicative of immunity. Results: Of the 1,813 sera tested, 82% were antibody positive for poliovirus type 1 and 88% were positive for type 2. Immunity to type 3 poliovirus was lower overall (74%) and especially in school-aged children and young adults. For all three poliovirus types, there were more females immune than males and immunity peaked in the 2-4 years age group. The proportion of the population immune to all three types was 59%, and 3% were negative for all three types. Conclusions and Implications: This is the first national serosurvey for immunity to poliovirus in Australia. Herd immunity is probably sufficient to prevent generalised outbreaks due to type 1 and 2 poliovirus, but this may not be the case for type 3. However, localised outbreaks of any poliovirus type could still occur following reintroduction unless uniformly high levels of vaccination coverage are maintained. Ongoing serosurveillance is required following the recent change back to inactivated polio vaccine.

关键词： Amino Acid Sequence   Animals   Antibodies   Monoclonal   immunology   Antibodies   Viral   immunology   Base Sequence   Cell Line   Tumor   Cysteine Endopeptidases   metabolism   Cytopathogenic Effect   Viral   immunology   Hela Cells   Humans   Membrane Proteins   immunology   MolecularSequence Data   Neurons   virology   Poliovirus   immunology   pathogenicity   Receptors   Virus   immunology   Research Support   Non-U.S. Gov't   Sequence Analysis   DNA   Viral Proteins   metabolism   VirusReplication  

摘要： The poliovirus (PV)-induced cytopathic effect (CPE) was blocked in neural cells but not in HeLa cells by the addition of monoclonal antibody (MAb) against PV or the human PV receptor (CD155) 2 h postinfection (hpi). Since each MAb has the ability to block viral infection, no CPE in PV-infected neural cells appeared to result from the blockade of multiple rounds of viral replication. Pulse-labeling experiments revealed that virus-specific protein synthesis proceeded 5 hpi with or without MAbs. However, in contrast to the results obtained without MAbs, virus-specific protein synthesis with MAbs was not detected 7 hpi. Shutoff of host translation was also not observed in the presence of MAbs. Western blot analysis showed that 2A(pro), the viral protein which mediates the cleavage of eukaryotic translation initiation factor eIF4G, was still present 11 hpi. However, intact eIF4G appeared 11 hpi. An immunocytochemical study indicated that 2A(pro) was detected only in the nucleus 11 hpi. These results suggest that neural cells possess protective response mechanisms against PV infection as follows: (i) upon PV infection, neural cells produce a factor(s) to suppress PV internal ribosome entry site activity by 7 hpi, (ii) a factor which supports cap-dependent translation for eIF4G may exist in infected cells when no intact eIF4G is detected, and (iii) the remaining 2A(pro) is not effective in cleaving eIF4G because it is imported into the nucleus by 11 hpi.

关键词： .log   polypropylene   divalent   Viral inactivation   Poliovirus   Container   adhesion-aggregation phenomena   viral survival   viral loss  

摘要： Viral inactivation and adhesion-aggregation in water are often studied as separate phenomena. When the focus is placed on viral adhesion-aggregation, inactivation is neglected because the phenomena under investigation occur over a short period measured in days. When viral inactivation is studied, adhesion-aggregation phenomena are considered to be negligible because viral survival is traced over several days or months. In the present work, eve took a global approach, examining the relative contributions of each of these processes in a complex system composed of groundwater, Poliovirus 1, and a hydrophobic container (polypropylene) maintained in a dark environment at 20degreesC. We demonstrated that infectious viral load fell off 2.8 logo during the first 20 days. During this time, adhesion was far from negligible because it accounted for most of the decline, 1.5 log(10). Adhesion was undoubtedly favored by the presence of divalent ions in the groundwater. After 20 days, aggregation may also have been the cause of 0.66 to 0.92 log(10) of viral loss. Finally, viral inactivation was quantitatively the lowest phenomena because it only explained 0.38 to 0.64 log(10) of the viral loss. This study thus clearly demonstrated that estimates of viral survival in a given system must always take into account adhesion-aggregation phenomena which may be responsible for the majority of viral loss in the aqueous phase. Adhesion and aggregation are reversible processes which may lead to an underestimation of viral load in certain studies.

关键词： poliovirus   host response to viral infection   apoptosis   cytopathic effect   caspases   TUNEL  

摘要： In several cell types, poliovirus activates the apoptotic program, implementation of which is suppressed by viral antiapoptotic functions. In such cells, productive infection leads to a necrotic cytopathic effect (CPE), while abortive reproduction, associated with inadequate viral antiapoptotic functions, results in apoptosis. Here, we describe two other types of cell response to poliovirus infection. Murine L20B cells expressing human poliovirus receptor responded to the infection by both CPE and apoptosis concurrently. Interruption of productive infection decreased rather than increased the proportion of apoptotic cells. Productive infection was accompanied by the early efflux of cytochrome c from the mitochondria in a proportion of cells and by activation of DEVD-specific caspases. Inactivation of caspase-9 resulted in a marked, but incomplete, prevention of the apoptotic response of these cells to viral infection. Thus, the poliovirus-triggered apoptotic program in L20B cells was not completely suppressed by the viral antiapoptotic functions. In contrast, human rhabdomyosarcoma RD cells did not develop appreciable apoptosis during productive or abortive infection, exhibiting inefficient efflux of cytochrome c from mitochondria and no marked activation of DEVD-specific caspases. The cells were also refractory to several nonviral apoptosis inducers. Nevertheless, typical caspase-dependent signs of apoptosis in a proportion of RD cells were observed after cessation of viral reproduction. Such "late" apoptosis was also observed in productively infected HeLa cells. In addition, a tiny proportion of all studied cells were TUNEL positive even in the presence of a caspase inhibitor. Degradation of DNA in such cells appeared to be a postmortem phenomenon. Biological relevance of variable host responses to viral infection is discussed. (C) 2004 Elsevier Inc. All rights reserved.

关键词： H. pylori   vaccine   poliovirus vector  

摘要： We developed a novel vaccine for Helicobacter pylori based on a poliovirus vector in which capsid genes were replaced with the gene for the B subunit of H. pylori urease (UreB). Mice were vaccinated with UreB or control (LI) replicon and challenged with H. pylori. Twenty percent of mice vaccinated prophylactically with UreB, but 80% vaccinated with LI, and then challenged with H. pylori became infected (P = 0.003). Seventy-three percent of mice with established H. pylori infection vaccinated therapeutically with UreB replicon cleared their infection compared to 33% vaccinated with LI (P = 0.067). In therapeutically vaccinated mice with residual infection, UreB-vaccinated animals had fewer H. pylori than L1-vaccinated mice (P < 0.05). Anti-urease antibody titres in prophylactically, but not therapeutically, vaccinated mice were markedly higher in animals that received UreB versus LI replicon (P = 0.01). Vaccination with poliovirus vector containing the gene for the B subunit of H. pylori urease provides significant prophylactic and strong therapeutic protection against H. pylori in mice. (C) 2004 Published by Elsevier Ltd.

关键词： 脊髓灰质炎   疫苗   强化免疫   莱芜市   2003年   2004年   免疫活动   计划免疫  

摘要： [目的 ]评价莱芜市 2 0 0 3 /2 0 0 4年脊髓灰质炎 (脊灰 )疫苗强化免疫情况 ,为消灭脊灰提供依据。 [方法 ]接种率现场快速调查评估与计算估算接种率相结合。 [结果 ] 2轮报告接种率分别为 98 67%、97 10 % ,估算接种率分别为92 86%、93 82 % ;快速评估 2轮调查接种率分别为 95 0 5 %、93 0 7% ,农村高于城区 ,常住儿童高于流动儿童。 [结论 ]本次强化免疫接种率指标达到了省卫生厅要求 ,但城区和流动儿童的计划免疫工作还需要进一步加强。