Natural History and Pathogenesis of WNV in Viremic Dono*

漫游。 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 脑膜脑炎当症状出现时，病毒血症通常已经清除，免疫反应 进化，使其难以准确描述感染的临床谱或研究相互作用， 病毒和免疫系统之间的联系当西尼罗河病毒RNA筛选时， 2003年中期，美国开始实施核酸扩增检测（NAT）。Nat 筛选将允许表征急性病毒血症的动力学和免疫应答的时间过程 原发性西尼罗河病毒感染。前瞻性招募病毒血症、血清转化前供体，并详细 临床、病毒学和免疫学研究将更好地确定感染的自然史和病毒， 与病毒血症和各种西尼罗河病毒病综合征控制相关的宿主因素。我们将绘制我们的 来自美国红十字会（ARC）和血液检测的病毒血症个体的独特队列的样本 美国血液系统协会（BSI）的血库网络收集了大约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。一个病毒血症供体的子集， 出现严重症状感染者和匹配的无症状对照者，将入组一个亚组， study.我们将对频繁的连续样本进行病毒学和免疫学分析， 原发性病毒血症的动力学和WNV特异性IgM、伊加、IgG和空斑中和的时间过程 抗体血清转换。T细胞应答的详细研究，包括动力学和抗原特异性，以及 将在相同的病例中进行细胞因子扰动。这些研究的结果将 解决关键的血液安全问题，并有助于我们了解自然史和发病机制 通过鉴定与病毒血症控制相关的病毒和体液免疫参数来检测西尼罗河病毒感染。

ROVlDED. Jntil 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 administerinterviews (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 sub- study. 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.