Pathophysiology of HTLV-I and HTLV-II Infection

HTLV-I 和 HTLV-II 感染的病理生理学

• 批准号: 6872577
• 负责人: EDWARD L MURPHY
• 金额: $ 95.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-12 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6872577
• 关键词: Retroviridae disease; acute bronchitis; arthritis; autoimmune disorder; clinical research; comorbidity; epidemiology; human T cell lymphotropic virus type 1; human T cell lymphotropic virus type 2; human subject; medical complication; pathologic process; patient oriented research; pneumonia; spinal cord disorders

DESCRIPTION (provided by applicant): Despite an estimated 1 million case of human T-lymphotropic virus type I (HTLV-I) infection worldwide, and over 197,000 cases of infection with HTLV-II in the United States, the clinical outcomes and pathogenesis of HTLV-I and -II infection are still not well defined. Data from the previous funding period of this HTLV Outcomes Study (HOST) indicate that HTLV-II predisposes to pneumonia, bronchitis and arthritis, causes a myelopathy similar to HTLV-I associated myelopathy (HAM), and is associated with increased all-cause mortality. HTLV-I has previously been associated with adult T-cell leukemia (ATL), HAM and arthritis, uveitis and iritis. These pulmonary, neurologic and immunologic syndromes have not been well characterized clinically or biologically, especially for HTLV-II. This Competing Continuation Project will test the following hypotheses: 1. Infection with HTLV-II, and to a lesser degree HTLV-I, predisposes to pneumonia and bronchitis because of HTLV-induced, immune-mediated pulmonary damage. 2. HTLV-II causes myelopathy resembling HTLV-I associated myelopathy (HAM) via similar mechanisms immune-mediated neurotoxicity. 3. HTLV-II, and perhaps HTLV-I, is associated with increased mortality, perhaps due to a higher death rate from malignant and/or cardiovascular causes. 4. HTLV-I and -II are associated with a higher incidence of arthritis and other autoimmune conditions. We shall test these hypotheses during additional prospective investigation of the HOST cohort of 154 HTLVI, 387 HTLV-II and 799 stratum matched seronegative former blood donors enrolled in 1990-92. 6 biennial visits of this cohort have been completed to date. This application proposes 2 additional visits from 2005 through 2009, including structured health interviews, screening physical examinations, medical record review and targeted physician diagnostic work-ups. Blood will be collected from all subjects, and bronchoalveolar lavage fluid and cerebrospinal fluid from subsets with disease, for studies of HTLV virology and immunology.

描述（由申请方提供）：尽管全世界估计有100万例人嗜T淋巴细胞病毒I型（HTLV-I）感染，美国有超过197，000例HTLV-II感染，但HTLV-I和HTLV-II感染的临床结局和发病机制仍不明确。来自该HTLV结局研究（HOST）的前一个资助期的数据表明，HTLV-II易患肺炎、支气管炎和关节炎，引起与HTLV-I相关的脊髓病（HAM）相似的脊髓病，并与全因死亡率增加相关。HTLV-I以前与成人T细胞白血病（ATL）、HAM和关节炎、葡萄膜炎和虹膜炎相关。这些肺、神经和免疫综合征在临床或生物学上尚未得到很好的表征，尤其是HTLV-II。这个竞争延续项目将测试以下假设：1。感染HTLV-II和较小程度的HTLV-I，由于HTLV诱导的免疫介导的肺损伤，易患肺炎和支气管炎。2. HTLV-II通过与免疫介导的神经毒性类似的机制引起类似于HTLV-I相关脊髓病（HAM）的脊髓病。3. HTLV-II，可能还有HTLV-I，与死亡率增加有关，可能是由于恶性和/或心血管原因的死亡率较高。4. HTLV-I和HTLV-II与关节炎和其他自身免疫性疾病的发病率较高相关。我们将在1990-92年入组的154例HTLVI、387例HTLV-II和799例分层匹配的血清阴性前献血者的HOST队列的额外前瞻性研究中检验这些假设。迄今为止，该队列已完成6次两年期访视。这项申请提议在2005年至2009年期间增加两次访问，包括有组织的健康面谈、筛查性体格检查、病历审查和有针对性的医生诊断检查。将采集所有受试者的血液以及疾病亚组的支气管肺泡灌洗液和脑脊液，用于HTLV病毒学和免疫学研究。