Virus Detection Using Microarrays and Characterization of a Novel Cardiovirus

描述（由申请人提供）：这是一份K 08奖的申请书，申请人是加州大学旧金山分校弗朗西斯科成人传染病研究员和生物物理学博士学位的第三年博士后研究员。UCSF是一个领先的学术生物医学研究中心，拥有强大的临床和研究社区。这里提出的工作将有助于建立候选人作为一个独立的翻译研究传染病。候选人提出的研究的总体目标是使用创新的泛病毒DNA微阵列（Virochip）来检测和发现与人类呼吸道感染相关的病毒。急性呼吸道感染给社会带来了重大的经济和卫生保健负担。病毒与下呼吸道和上呼吸道疾病有关，但无法确定特定的病原体 在30-60%的情况下。候选人在初步实验中证明，病毒芯片是 在灵敏度和特异性方面与常规临床诊断测试相当，并且Virochip能够检测逃避所有当前可用的诊断测定的病毒。在拟议的研究中，候选人将使用病毒芯片回顾性分析33名急性呼吸窘迫综合征患者的支气管肺泡灌洗液样本（Aim 1a），并前瞻性分析ICU中15-20名重症患者的呼吸分泌物（Aim 1b）是否存在病毒。为了确定检测到的病毒和呼吸道疾病之间的潜在因果关系，候选人将评估特定的抗体反应，并在其他体液和组织中寻找病毒。为了寻找与呼吸道疾病相关的新型病毒，候选人还将使用病毒芯片筛选加州卫生服务部（Aim 2）收集的培养阴性和病毒PCR阴性呼吸道样本。候选人希望通过该筛选发现潜在的新型病毒，然后他将继续测序并开发针对这些病毒的特定血清学或基于PCR的检测方法。相关性：了解危重呼吸道疾病的病毒病因可能有助于指导这些危及生命的感染的预防、诊断和治疗。新呼吸道病毒的发现将对临床实践和公共卫生产生重大影响，并可能刺激新的抗病毒药物和疫苗的开发。

DESCRIPTION (provided by applicant): This is an application for a K08 award for Dr. Charles Chiu, a fellow in adult infectious diseases at the University of California, San Francisco and a 3rd year postdoctoral research fellow with a PhD in biophysics. UCSF is a leading academic biomedical research center with a strong clinical and research community. The work proposed here will help establish the candidate as an independent translational investigator in infectious diseases. The overall goal of the candidate's proposed research is to use an innovative pan-viral DNA microarray (Virochip) to detect and discover viruses associated with human respiratory infection. Acute respiratory tract infection imposes a major economic and health care burden on society. Viruses are associated with both lower and upper respiratory tract illnesses, yet a specific pathogen cannot be identified in 30-60% of cases. The candidate has demonstrated in preliminary experiments that the Virochip is comparable in sensitivity and specificity to that of routine clinical diagnostic tests and that the Virochip is capable of detecting viruses that elude all currently available diagnostic assays. For the proposed research, the candidate will use the Virochip to retrospectively analyze samples of bronchoalveolar lavage fluid from 33 patients with acute respiratory distress syndrome (Aim 1a) and prospectively analyze respiratory secretions from 15-20 critically ill patients in the ICU (Aim 1b) for the presence of viruses. To determine a potential causal relationship between a detected virus and the respiratory illness, the candidate will assess specific antibody responses and look for the virus in other bodily fluids and tissues. To search for novel viruses associated with respiratory illness, the candidate will also use the Virochip to screen culture-negative and viral PCR-negative respiratory samples collected by the California Department of Health Services (Aim 2). The candidate expects that potentially novel viruses will be discovered from this screen, and he will then proceed to sequence and develop specific serological or PCR-based assays for these viruses. Relevance: Understanding viral etiologies of critical respiratory illness may help guide prevention, diagnosis, and treatment of these life-threatening infections. Discovery of a novel respiratory virus would have significant implications on clinical practice and public health and may stimulate development of new antiviral drugs and vaccines.