Natural History and Pathogenesis of WNV in Viremic Dono*

病毒血症 Dono 中西尼罗河病毒的自然史和发病机制*

• 批准号: 7119236
• 负责人: MICHAEL Paul BUSCH
• 金额: $ 20万
• 依托单位: VITALANT
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7119236
• 关键词: T lymphocyte; West Nile virus; clinical research; disease /disorder etiology; enzyme linked immunosorbent assay; epitope mapping; host organism interaction; human subject; humoral immunity; hyperthermia; immunoglobulin A; immunoglobulin G; immunoglobulin M; microorganism immunology; nervous system disorder; neutralizing antibody; nucleic acid amplification techniques; questionnaires; serology /serodiagnosis; sign /symptom; virus cytopathogenic effect; virus genetics; virus load

Description (provided by applicant): Until recently, most humans identified with WNV infection presented with symptoms of WNV fever or meningoencephalitis. By the time symptoms appear, viremia has typically cleared and immune responses evolved, making it difficult to accurately characterize the clinical spectrum of infection or study the interplay between the virus and the immune system. This situation changed dramatically when WNV RNA screening of blood donors using nucleic acid amplification tests (NAT) was implemented in the U.S. in mid-2003. NAT screening will allow characterization of the dynamics of acute viremia and time course of immune responses in primary WNV infection. Prospective enrollment of viremic, pre-seroconversion donors and detailed clinical, virologic and immunologic studies will better define the natural history of infection and the viral and host factors that correlate with control of viremia and varied WNV disease syndromes. We will draw our samples from a unique cohort of viremic individuals detected by the American Red Cross (ARC) and Blood Systems (BSI) networks of blood banks, which together collect approximately 60% of the U.S. blood supply. Medical staff at ARC and BSI will administer interviews (developed in collaboration with CDC) to ascertain the rates of development and severity of WNV-symptom complexes. A subset of viremic donors who develop severe symptomatic infections and matched asymptomatic controls, will be enrolled into a substudy. We will perform virologic and immunologic analyses of frequent sequential samples to characterize the kinetics of primary viremia and the time course of WNV-specific IgM, IgA, IgG and plaque neutralizing antibody seroconversion. Detailed studies of T cell responses, including kinetics and antigen specificity, and of cytokine perturbations will be carried out on the same cases. The findings from these studies will therefore address key blood safety issues and contribute to our understanding of the natural history and pathogenesis of WNV infection by identifying viral and humoral immune parameters that correlate with control of viremia.

描述（由申请人提供）：直到最近，大多数被确定为西尼罗河病毒感染的人都表现出西尼罗河病毒发热或脑膜脑炎的症状。当症状出现时，病毒血症通常已经清除，免疫反应已经发展，因此很难准确描述感染的临床谱或研究病毒与免疫系统之间的相互作用。2003年中期，当美国使用核酸扩增试验（NAT）对献血者进行西尼罗河病毒RNA筛查时，这种情况发生了巨大变化。NAT筛选将允许表征急性病毒血症的动态和免疫反应的时间过程中的主要西尼罗河病毒感染。前瞻性招募病毒血症、血清转化前供体和详细的临床、病毒学和免疫学研究将更好地确定感染的自然史以及与病毒血症和各种WNV疾病综合征控制相关的病毒和宿主因素。我们将从美国红十字会（ARC）和血液系统（BSI）血库网络检测到的病毒血症个体中抽取样本，这些血库共收集了约60%的美国血液供应。ARC和BSI的医务人员将进行访谈（与CDC合作开发），以确定WNV症状复合体的发展速度和严重程度。发生重度症状性感染的病毒血症供体亚组和匹配的无症状对照将入组子研究。我们将对频繁的连续样本进行病毒学和免疫学分析，以表征原发性病毒血症的动力学以及WNV特异性IgM、伊加、IgG和空斑中和抗体血清转换的时间过程。将对相同病例进行T细胞应答（包括动力学和抗原特异性）和细胞因子扰动的详细研究。因此，这些研究的结果将解决关键的血液安全问题，并通过确定与病毒血症控制相关的病毒和体液免疫参数，有助于我们了解西尼罗河病毒感染的自然史和发病机制。