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）：流行角膜结膜炎（EKC）是由腺病毒亚组病毒血清型8、19和37引起的，是人类最常见的眼睛感染之一，导致了重大的发病率和经济影响。 EKC具有高度传染性的，急性表现出严重的结膜炎和上皮角膜炎，并且与基质（下皮下）角膜炎的延迟发育有关。 次要干眼，光敏度和视力模糊可以无限期持续。 令人惊讶的是，尽管腺病毒组被确定为40年前EKC的原因，但导致EKC的腺病毒血清型的遗传学仍然很大程度上是未知的。 我们的长期目标是开发基于信息的新方法来预防和治疗该疾病。 我们假设与EKC相关的腺病毒的遗传分析将揭示特定的病毒发病机理特征，部分决定了该疾病的表现。 因此，该R03提案特别解决了有关这些腺病毒遗传学的严重缺乏信息，因此填补了RO3奖的既定目的，因为我们建议获得“对视力研究产生高影响的数据体”。科学界已经收到了阐明其他人类病原体的遗传代码的最新类似努力。 首席研究员，一名临床医生科学家之间的合作，具有广泛的病毒学和眼科感染疾病专业知识，而共同研究者是一名微生物遗传学家，他将他的职业生涯致力于我们的职业生涯，这可能会导致我们提出的那种研究，可能会导致非常重要的和医学上相关的序列序列数据的解释。 最重要的是，拟议的工作的成功完成将允许目前无法以一种可能的方式研究眼病毒感染的病毒学。我们提出了一个单一的特定目的：确定和比较来自EKC患者的临床腺病毒分离株的遗传序列。 为此，将从临床眼科的三个主要中心收集腺病毒并测序。 对于其他科学家来说，通过我们的网站可以免费访问我们的数据。 将使用序列比对和分析软件进行核苷酸和预测氨基酸序列差异的其他亚组D腺病毒的比较，并有望揭示未来研究的潜在发病机理特征。