Genetics of Ocular Adenoviruses

眼腺病毒的遗传学

• 批准号: 7001204
• 负责人: James Chodosh
• 金额: $ 14.31万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7001204
• 关键词: Adenoviridae; bioinformatics; human tissue; keratoconjunctivitis; nucleic acid sequence; polymerase chain reaction; protein sequence; restriction fragment length polymorphism; serotyping; tissue /cell culture; virus cytopathogenic effect; virus genetics

DESCRIPTION (provided by applicant): Epidemic keratoconjunctivitis (EKC) is caused by infection with the subgroup D adenovirus serotypes 8, 19, and 37, and is one of the most common human eye infections, causing significant morbidity and economic impact. EKC in highly contagious, manifests acutely with severe conjunctivitis and epithelial keratitis, and is associated with the delayed development of stromal (subepithelial) keratitis. Secondary dry eye, light sensitivity, and blurred vision can persist indefinitely. Surprisingly, although a group D adenovirus was identified as the cause of EKC over 40 years ago, the genetics of the adenovirus serotypes that cause EKC remain largely unknown. Our long term goal is to develop novel information-based approaches to prevention and therapy of the disorder. We hypothesize that genetic analyses of the adenoviruses associated with EKC will reveal specific viral pathogenesis traits that determine in part the manifestations of the disorder. This R03 proposal therefore specifically addresses a critical lack of information with regards to the genetics of these adenoviruses, and as such fills a stated purpose of the RO3 award, in that we propose to acquire "a body of data that has a potentially high impact on vision research". Recent similar efforts to elucidate the genetic code for other human pathogens have been received by the scientific community as seminal. The proposed collaboration between the principal investigator, a clinician-scientist with extensive expertise in virology and ocular infectious disorders, and the co-investigator, a microbial geneticist who has devoted his professional career to just the sort of study we propose, will likely result in highly significant and medically relevant interpretations of the resulting sequence data. Most importantly, successful completion of the proposed work will allow the study of the virology of ocular adenovirus infection in a fashion not currently possible. We propose a single specific aim: to determine and compare the genetic sequences of clinical adenovirus isolates from patients with EKC. To this end, adenoviruses will be collected from three major centers of clinical ophthalmology and sequenced. To other scientists, access to our data will be free and unencumbered via our web site. Genome-wide comparisons with other subgroup D adenoviruses for differences in nucleotide and predicted amino acid sequences will be performed using sequence alignment and analysis software, and are expected to reveal potential pathogenesis traits for future study.

描述（由申请人提供）：流行性角结膜炎（EKC）是由 D 亚型腺病毒血清型 8、19 和 37 感染引起的，是最常见的人眼感染之一，造成显着的发病率和经济影响。 EKC 具有高度传染性，表现为严重的结膜炎和上皮性角膜炎，并与基质（上皮下）角膜炎的延迟发展有关。 继发性干眼、光敏感和视力模糊可能会无限期持续。 令人惊讶的是，尽管 D 组腺病毒在 40 多年前就被确定为 EKC 的病因，但引起 EKC 的腺病毒血清型的遗传学仍然很大程度上未知。 我们的长期目标是开发新的基于信息的方法来预防和治疗这种疾病。 我们假设对与 EKC 相关的腺病毒进行遗传分析将揭示特定的病毒发病机制特征，这些特征在一定程度上决定了该疾病的表现。 因此，这项 R03 提案专门解决了有关这些腺病毒遗传学的严重缺乏信息的问题，因此满足了 RO3 奖项的既定目的，即我们建议获取“对视觉研究”。最近为阐明其他人类病原体的遗传密码所做的类似努力已被科学界认为具有开创性。 首席研究员（一位在病毒学和眼部传染病方面拥有丰富专业知识的临床医生科学家）与共同研究员（一位将其职业生涯奉献给我们提议的研究的微生物遗传学家）之间拟议的合作可能会导致对所得序列数据具有高度显着性和医学相关性的解释。 最重要的是，成功完成拟议的工作将使以目前不可能的方式研究眼腺病毒感染的病毒学。我们提出了一个具体目标：确定并比较来自 EKC 患者的临床腺病毒分离株的基因序列。 为此，将从三个主要临床眼科中心收集腺病毒并进行测序。 对于其他科学家来说，通过我们的网站可以免费且不受阻碍地访问我们的数据。 将使用序列比对和分析软件与其他 D 亚组腺病毒进行全基因组比较，以了解核苷酸和预测氨基酸序列的差异，并有望揭示未来研究的潜在发病机制特征。