STRUCTURE AND EXPRESSION OF PNEUMOCYSTIS ANTIGEN GENES

肺孢子虫抗原基因的结构和表达

• 批准号: 6631867
• 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/6631867
• 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.

提出的工作集中在MSG上，MSG是致病真菌卡氏肺孢子虫的一组可变表面抗原。 表面抗原如MSG是基本感兴趣的，因为它们在宿主-病原体界面起作用。 这种界面对病原微生物的重要性通过某些原生动物和细菌用于在其表面产生多样性的复杂遗传系统来说明。 卡氏肺孢子虫MSG基因似乎赋予这种真菌类似的能力，以改变其表面。 提出的研究的广泛，长期的目标是表征卡氏肺孢子虫的抗原变异，了解控制它的遗传机制，并研究抗原变异和宿主-病原体相互作用之间的关系。 实验主要集中在大鼠卡氏肺孢子虫上，因为它易于处理。 对人类卡氏肺孢子虫的研究也提出了建议。待测试的假设包括（i）卡氏肺孢子虫使用DNA重组来改变连接到独特表达位点的MSG基因。(ii)改变这个基因会导致细胞表面的MSG发生变化。(iii)感染人类的卡氏肺孢子虫具有与感染大鼠的卡氏肺孢子虫相似的MSG表达系统。 本研究有以下四个具体目的：1。确定抗原变异的遗传基础。 2.分析接种大鼠模型中MSG变化的动态和性质。 3：确定宿主免疫应答是否影响抗原变异的频率或性质。 4.分析人卡氏肺吸虫的MSG系统。 将使用自然感染的大鼠和接种低剂量卡氏肺孢子虫的大鼠来解决这些目标。将从患者中获得人卡氏肺孢子虫。 分子遗传学和免疫组织化学工具将用于研究MSG基因和蛋白质的表达。