STRATEGIC TARGETING OF VIRAL GENOMES IN BILIARY ATRESIA

胆道闭锁中病毒基因组的策略性靶向

• 批准号: 7599257
• 负责人: PHILLIP I TARR
• 金额: $ 15.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-10 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7599257
• 关键词: Age; Ancillary Study; Archives; Base Sequence; Biliary Atresia; Classification; Conflict (Psychology); Conserved Sequence; Coronavirus; DNA Microarray Chip; Diagnosis; Disease; Disease Outbreaks; Etiology; Future; Genbank; Genomics; Infant; Investigation; Laboratories; Liver; Liver diseases; Methodology; Methods; Nucleic acid sequencing; Oligonucleotides; Pan Genus; Patients; Pattern; Perinatal; Phenotype; Play; Prevention; Probability; Research; Role; Sampling; Serological; Serum; Severe Acute Respiratory Syndrome; Specimen; Syndrome; Technology; Testing; Time; Tissues; Universities; Viral; Viral Genome; Virus; Virus Diseases; Washington; alpha 1-Antitrypsin Deficiency; bile duct; infancy; interest; neonatal hepatitis; novel; novel virus; repository; viral detection; viral liver disease

DESCRIPTION (provided by applicant): We hypothesise that viral infection could play an etiologic role in biliary atresia (BA), one of the most serious digestive/liver diseases of infancy. However, to date attempts to isolate or discover viruses in patients with BA have been limited to small numbers of patients, have yielded conflicting results, and the methodology has been limited to serological, and/or tissue analysis looking for known viruses. The Biliary Atresia Research Consortium's (BARC) tissue repository offers the opportunity for systematic search for the long-suspected viral etiology of this disease and this BARC Ancillary Study proposes to apply a powerful and novel method of viral discovery, using a DNA microarray harboring the most highly conserved 70mer oligonucleotide sequences from every fully sequenced viral genome in GenBank. Strategic targeting of the conserved regions of viral genomes enables not only massively parallel analysis of essentially all known viruses, but also maximizes the probability of detecting unknown viruses. Identification of a viral etiology should serve as the launching point for additional studies focused on disease mechanisms, treatment and prevention. This proposal aims to apply this powerful and novel methodology to the investigation of a possible viral etiology of BA, by examining liver and bile duct remnants from EHBA patientsenrolled in the BARC with the `acquired' or `perinatal' phenotype. A small number of tissues will be examined from patients with the `embryonal' phenotype, and from patients with known non-viral liver diseases eg alpha-1-antitrypsin deficiency, allagille syndrome etc. as control tissue. Dr Wang's laboratory at Washington University St Louis has been at the forefront of new viral discovery. For example, during the recent SARS outbreak, hybridization patterns observed using the pan-viral microarray helped identify SARS as a novel coronavirus, demonstrating the power and utility of this approach.

描述（由申请人提供）：我们假设病毒感染可能在胆道闭锁（BA）中发挥病因作用，胆道闭锁是婴儿期最严重的消化/肝脏疾病之一。然而，迄今为止，在 BA 患者中分离或发现病毒的尝试仅限于少数患者，并产生了相互矛盾的结果，并且方法仅限于寻找已知病毒的血清学和/或组织分析。胆道闭锁研究联盟 (BARC) 的组织储存库为系统性搜索该疾病长期怀疑的病毒病因提供了机会，这项 BARC 辅助研究建议应用一种强大而新颖的病毒发现方法，使用含有最多病毒的 DNA 微阵列。来自 GenBank 中每个已完全测序的病毒基因组的高度保守的 70mer 寡核苷酸序列。对病毒基因组保守区域的战略定位不仅可以对基本上所有已知病毒进行大规模并行分析，还可以最大限度地提高检测未知病毒的可能性。病毒病因学的鉴定应作为针对疾病机制、治疗和预防的其他研究的起点。 该提案旨在通过检查 BARC 中具有“获得性”或“围产期”表型的 EHBA 患者的肝脏和胆管残余物，将这种强大而新颖的方法应用于 BA 可能的病毒病因学调查。将检查来自具有“胚胎”表型的患者和患有已知非病毒性肝病例如α-1-抗胰蛋白酶缺乏症、allagille综合征等的患者的少量组织作为对照组织。王博士位于圣路易斯华盛顿大学的实验室一直处于新病毒发现的前沿。例如，在最近的 SARS 爆发期间，使用泛病毒微阵列观察到的杂交模式有助于将 SARS 识别为新型冠状病毒，证明了这种方法的威力和实用性。