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以在胆道闭锁（BA）中起病因，这是婴儿期最严重的消化/肝脏疾病之一。但是，迄今为止，试图分离或发现BA患者的病毒已限于少量患者，结果矛盾，并且该方法仅限于血清学和/或组织分析，寻找已知病毒。胆道闭锁研究联盟（BARC）组织存储库为系统搜索这种疾病的长期探索病毒病因提供了机会，这项BARC辅助研究建议采用一种强大而新颖的病毒发现方法，使用DNA微阵列具有最高的70mer寡核核苷序列，这些DNA微阵列与每个完全辅助的构造构造了构成基因的基因构成的基因。病毒基因组保守区域的战略靶向不仅可以对所有已知病毒进行大规模平行分析，而且还可以最大程度地分析检测未知病毒的可能性。病毒病因的鉴定应作为涉及疾病机制，治疗和预防的其他研究的发射点。 该提案旨在通过检查从BARC中使用“获得”或“围产期”表型的EHBA患者的肝脏和胆管残留物，将这种强大而新颖的方法应用于对BA的可能病毒病因的研究。将检查少数组织的“胚胎”表型患者，以及已知的非病毒肝疾病的患者，例如α-1-抗抗蛋白酶缺乏症，Allagille综合征等作为对照组织。华盛顿大学圣路易斯博士的实验室一直处于新病毒发现的最前沿。例如，在最近的SARS爆发中，使用泛病毒微阵列观察到的杂交模式有助于将SARS识别为一种新型的冠状病毒，证明了这种方法的功能和实用性。