CYTOMEGALOVIRUS PNEUMONITIS: THE ROLE OF TNF A AND B

巨细胞病毒肺炎：TNF A 和 B 的作用

• 批准号: 3348191
• 负责人: John D Shanley
• 金额: $ 22.54万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3348191
• 关键词: Betaherpesvirinae; Herpesviridae disease; Pneumocystis pneumonia; cytokine; disease /disorder model; gene expression; graft versus host disease; immunochemistry; immunopathology; laboratory mouse; lung; nucleic acid hybridization; temperature sensitive mutant; tumor necrosis factor alpha; tumor necrosis factor beta; viral pneumonia; virus antigen; virus cytopathogenic effect; virus replication

DESCRIPTION: (Adapted from the applicant's abstract.) While serious CMV infections can involve a number of host tissues, the lungs are frequently involved in lethal CMV infections. In these experiments several murine models of CMV infection will be utilized in order to explore the cytokines, TNF-a and lymphotoxin (TNF-b), as mediators of tissue damage. The role of TNF-a and b in acute MCMV infection following sublethal and lethal virus challenge will be examined. Using a model of acute CMV infection, the amount of TNF expressed in tissue during lethal and sublethal virus challenge will be compared and the effect of exogenous TNF on acute CMV infection will be monitored. The effects of passive transfer of antibody to TNF on virus replication will be determined. To explore the role of TNF in lung injury, a murine model of pneumocystis associated MCMV and graft-versus-host disease will be used, comparing the levels of TNF during MCMV lung infection and pneumocystis. The production of TNF by lung cells during pneumocystis will be examined and it will be determined if production is antigen-specific or MHC-restricted. The effects of passive transfer of antibody to TNF and lymphotoxin on MCMV pneumocystis will also be determined. The Specific Aims of this project are: to determine the role of TNF-a and lymphotoxin in acute MCMV infection; and to determine the role of TNF-a and lymphotoxin in the pathogenesis of pneumocystis associated with combined MCMV infection and GVH disease.

描述：（改编自申请人的摘要。）虽然严重的 CMV 感染可涉及许多宿主组织，肺部经常受到感染 参与致命的 CMV 感染。 在这些实验中，一些小鼠 将利用 CMV 感染模型来探索细胞因子， TNF-a 和淋巴毒素 (TNF-b)，作为组织损伤的介质。 的作用 亚致死和致死病毒后急性 MCMV 感染中的 TNF-a 和 b 将审查挑战。 使用急性 CMV 感染模型， 致死和亚致死病毒期间组织中表达的 TNF 量 将比较挑战和外源性TNF对急性CMV的影响 将监测感染情况。 抗体被动转移的影响 TNF对病毒复制的影响将被确定。 探索TNF的作用 在肺损伤中，肺孢子虫相关 MCMV 的小鼠模型和 将使用移植物抗宿主病，比较移植期间的 TNF 水平 MCMV 肺部感染和肺孢子菌。 肺细胞产生TNF 在肺孢子虫期间将进行检查，并确定是否 生产是抗原特异性的或 MHC 限制的。 被动的影响 MCMV 肺孢子虫上的 TNF 和淋巴毒素抗体的转移也会 被确定。 该项目的具体目标是：确定 TNF-a 和淋巴毒素在急性 MCMV 感染中的作用；并确定 TNF-a和淋巴毒素在肺孢子菌发病机制中的作用 与 MCMV 感染和 GVH 疾病联合相关。