Receptor Mimics for Rapid Detection, Typing, and Susceptibility Testing of Influe

描述（由申请人提供）：因流感引起的疾病负担重大。在撰写本提案时，2009年H1N1流感大流行正在展开。截至2009年8月23日，世界卫生组织报告了超过209,438例经实验室确诊的2009年H1N1流感病毒病例，其中至少有2,185人死亡。能够检测该病毒对当前抗病毒药物敏感性的快速、准确、即时检测试剂盒在我们抗击这一致命病毒的斗争中至关重要。本提案的目的是开发新的基于糖的诊断平台，该平台针对病毒糖蛋白，血凝素（HA）和神经氨酸酶（NA），它们在病毒粒子表面丰富（约50个四聚体NA和300个三聚体HA）。该建议的基本原理是，设计良好的聚糖微阵列平台将产生暴露于病毒的“指纹识别模式”。这一建议的新颖之处在于，可以快速评估对达菲和乐感清的易感性，而无需耗时地识别和表征新出现的菌株。在特异性目标1中，我们将生成一个聚糖库来捕获和评估流感的抗病毒易感性。在具体目标2中，我们将开发不同的诊断平台来捕获和分类流感毒株。我们还将开发测试以确定对抗病毒药物的敏感性或耐药性。这些检测尤其重要，因为在确定抗病毒药抗性突变的基因组序列之前，目前没有快速检测和评估抗病毒药易感性的方法。在具体目标3中，我们将使用临床样本评估不同的平台。具体来说，我们将使用从感染患者中分离的临床样本来检查诊断平台的稳健性、敏感性和选择性，并评估抗病毒药物的易感性。实现本提案中的具体目标，预计将产生快速、可靠、即时护理、用户友好的诊断方法，以精确检测和区分不同的流感毒株。

DESCRIPTION (provided by applicant): Disease burden due to influenza is significant. The 2009 H1N1 pandemic is unfolding as this proposal is being written. As of August 23, 2009, over 209,438 laboratory-confirmed cases of 2009 H1N1 influenza viruses with at least 2,185 deaths have been reported by the World Health Organization. Rapid, accurate, point-of-care detection kits that possess the capability to test for susceptibility of the virus to current antivirals are critical in our fight against this deadly virus. The objective of this proposal is to develop novel glycan based diagnostic platforms that target the viral glycoproteins, Hemagglutinin (HA) and Neuraminidase (NA), which are abundant (~50 copies of tetrameric NA and 300 copies of trimeric HA) on the surface of the virion. The rationale for this proposal is that a well designed glycan microarray platform will yield a "fingerprint pattern of recognition" on exposure to the virus. The novelty of this proposal is that susceptibility to Tamiflu(r) and Relenza(r), can be rapidly evaluated without the time consuming need to identify and characterize an emerging strain. In Specific Aim 1, we will generate a library of glycans to capture and assess antiviral susceptibility of influenza. In Specific Aim 2, we will develop different diagnostic platforms to capture and type influenza strains. We will also develop tests to determine sensitivity or resistance to antiviral agents. These tests are especially important since there is currently no method to rapidly detect and assess antiviral susceptibility before the genomic sequence for antiviral resistance mutations has been determined. In Specific Aim 3, we will evaluate the different platforms using clinical samples. Specifically, we will examine the robustness, sensitivity, and selectivity of the diagnostic platforms using clinical samples isolated from infected patients and assess antiviral susceptibility. Accomplishing the specific aims in this proposal is expected to yield rapid, robust, point of care, user friendly diagnostics for the precise detection and differentiation of different influenza strains.