STRUCTURE AND EXPRESSION OF PNEUMOCYSTIS ANTIGEN GENES

肺孢子虫抗原基因的结构和表达

• 批准号: 6147592
• 负责人: JAMES Richard STRINGER
• 金额: $ 26.78万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6147592
• 关键词: Pneumocystis carinii; gene expression; genetic polymorphism; genetic recombination; host organism interaction; laboratory rat; microorganism genetics; polymerase chain reaction; protozoal antigen

The work proposed is focused on MSG, which is a group of variable surface antigens of the pathogenic fungus, P. carinii. Surface antigens such as MSG are of fundamental interest because they function at the host-pathogen interface. The importance of this interface to pathogenic microbes is illustrated by the complex genetic systems used by certain protozoa and bacteria to generate diversity on their surface. P. carinii MSG genes appear to endow this fungus with a similar capacity to vary its surface. The broad, long-term objectives of the research proposed are to characterize antigenic variation in P. carinii, to understand the genetic mechanism that controls it, and to study the relationship between antigenic variation and host-pathogen interactions. The experiments focus primarily on rat P. carinii because it is tractable. Studies on human P. carinii are also proposed. Hypotheses to be tested include (i) P. carinii use DNA recombination to change the MSG gene that is attached to a unique expression site. (ii) Changing this gene leads to a change in the MSG on the cell surface. (iii) P. carinii that infects humans has an MSG expression system similar to that in P.carinii that infects rats. The proposed research has the following four Specific Aims: 1. Determine the genetic basis for antigenic variation. 2. Analyze the dynamics and nature of MSG variation in the inoculated rat model. 3: Determine if the host immune response influences the frequency or nature of antigenic variation. 4. Analyze the MSG system in human P. carinii. These Aims will be addressed using rats that are naturally infected, and rats that have been inoculated with a low dose of P. carinii. Human P. carinii will be obtained from patients. Molecular genetic and immunohistochemical tools will be used to study expression of MSG genes and proteins.

拟议的工作重点是味精，它是致病真菌卡氏疟原虫的一组可变表面抗原。 味精等表面抗原具有重要意义，因为它们在宿主-病原体界面发挥作用。 某些原生动物和细菌利用复杂的遗传系统在其表面产生多样性，说明了这种界面对病原微生物的重要性。 P. carinii MSG 基因似乎赋予这种真菌类似的改变其表面的能力。 该研究的广泛、长期目标是表征卡氏疟原虫的抗原变异，了解控制其的遗传机制，并研究抗原变异与宿主-病原体相互作用之间的关系。 实验主要集中在大鼠 P. carinii 上，因为它很容易处理。 还提出了对人类卡氏疟原虫的研究。待测试的假设包括 (i) P. carinii 使用 DNA 重组来改变附着在独特表达位点上的 MSG 基因。 (ii) 改变该基因会导致细胞表面的味精发生变化。 (iii) 感染人类的​​卡氏疟原虫具有与感染大鼠的卡氏疟原虫相似的味精表达系统。 拟议的研究有以下四个具体目标： 1. 确定抗原变异的遗传基础。 2. 分析接种大鼠模型中味精变化的动态和性质。 3：确定宿主免疫反应是否影响抗原变异的频率或性质。 4. 分析人类 P. carinii 中的味精系统。 这些目标将通过使用自然感染的大鼠和接种低剂量卡氏疟原虫的大鼠来实现。人类卡氏疟原虫将从患者身上获得。 分子遗传学和免疫组织化学工具将用于研究味精基因和蛋白质的表达。