EARLY EVENTS IN THE PATHOGENESIS OF FIV INFECTION

五型感染发病的早期事件

• 批准号: 2072310
• 负责人: NIELS C PEDERSEN
• 金额: $ 30.6万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2072310
• 关键词: B lymphocyte; HIV infections; T lymphocyte; autoimmunity; cats; cyclosporines; cytokine; disease /disorder model; feline immunodeficiency virus; host organism interaction; immunodeficiency; in situ hybridization; pathologic process; polymerase chain reaction; protein biosynthesis; thalidomide; thymus; tissue /cell culture; tumor necrosis factor alpha

Human and feline immunodeficiency viruses (HIV and FIV) cause a similar disease syndrome in their respective host species. This disease syndrome evolves over years in three consecutive stages; acute, asymptomatic, and terminal. The acute state is referred to as "mononucleosis-like illness," while the terminal state is called AIDS in people and AIDS-like disease in cats. Of these 3 stages, the acute stage is the most important. It is during this acute illness that the first major decrease in CD4+ T cells occurs and when the life-long pattern of viral persistence is established. Many of the events in the terminal stage of infection are merely recapitulations of these early events, eg.g., viremia, accelerated decline in CD4+ T cells, lymphadenopathy, cytopenias. Certain biologic events that occur during acute illness are of particular importance: 1) the abrupt and permanent decline in CD4+ T cells, and 2) the establishment of a persistent infection. Therefore, the goal of the project is to study, in greater depth, certain biologic phenomena that have been observed during the acute stages of both FIV and IIIV infections, and to relate these events to immunodeficiency virus- mediated CD4+ T cell depletion and persistence. To this end, the specific aims of the study are: 1) To determine whether the primary immune response to lentivirus infections favors viral persistence over viral recovery as determined by the profile of cytokine responses in lymphoid organs. 2) Cyclosporine A treatment during the acute symptomatic and chronic asymptomatic stages of FIV infection and its comparative effects on the TH1 and TH2 pathway of cytokine activation. 3) To determine the role of TNF-alpha in the pathogenesis of FIV-induced disease. 4) To study the relation of early thymic lesions to the CD4+ T cell depletion that begins during the acute stage of FIV (and IIIV) infections. 5) To determine the significance of autoimmune phenomena that appear during the acute stages of FIV (and IIIV) infections.

人类和猫免疫缺陷病毒（HIV和FIV）引起类似的 疾病综合征在各自的宿主物种。 本病综合征 在三个连续的阶段发展多年;急性，无症状， 终端 急性状态被称为“类单核细胞增多症 病”，而艾滋病的终末期状态则称为人与艾滋病样 猫的疾病 在这3个阶段中，急性期最多 重要. 正是在这种急性疾病期间， 在CD 4 + T细胞中发生，当病毒的终身模式 持久性已经建立。 许多事件在最后阶段， 感染仅仅是这些早期事件的重演，例如， 病毒血症，CD 4 + T细胞加速下降，淋巴结病， 血细胞减少症 急性疾病期间发生的某些生物事件是 特别重要的是：1）CD 4 + T细胞的突然和永久性下降， 细胞，以及2）建立持续性感染。 因此，我们认为， 该项目的目标是更深入地研究某些生物 在FIV和FIV的急性期观察到的现象 IIIV感染，并将这些事件与免疫缺陷病毒- 介导的CD 4 + T细胞消耗和持续存在。 为此中央 研究的具体目标是： 1)为了确定对慢病毒的初次免疫应答是否 感染有利于病毒持久性超过病毒恢复，如通过以下测定的： 淋巴器官中细胞因子反应的概况。 2)环孢素A治疗急性症状性和慢性 FIV感染的无症状阶段及其对 细胞因子活化的TH 1和TH 2途径。 3)为了确定TNF-α在FIV诱导的肿瘤坏死因子（TNF-α）的发病机制中的作用， 疾病 4)探讨胸腺早期病变与CD 4 + T细胞的关系 在FIV（和IIIV）急性期开始的耗竭 感染. 5)为了确定出现的自身免疫现象的意义， 在FIV（和IIIV）感染的急性期。