Virus-host interactions in frog virus 3 infected cells

青蛙病毒 3 感染细胞中病毒与宿主的相互作用

• 批准号: 288123-2009
• 负责人: Brunetti, Craig
• 金额: $ 1.82万
• 依托单位: Trent University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=548114
• 关键词: Virus; host; interactions; frog; virus

The research outlined in this proposal is aimed at using a scientifically unexploited but economically important virus family, the Iridoviridae, to identify novel classes of virus-host interacting genes that will help identify previously unidentified cellular anti-viral pathways. We have chosen to look at virus-host interactions in the Iridoviridae for a number of reasons. First, unlike the Herpesviridae and Poxviridae families, there is a lack of significant basic research into the biology of the Iridoviridae. Secondly, by examining new viral families, novel genes that target uncharacterized host anti-viral strategies can be identified. Finally, many Iridoviridae have been confirmed as the causative agent of severe diseases in fish and wildlife, affecting aquaculture and wildlife conservation. To understand how the Iridoviridae family circumvents host defenses, we chose frog virus 3 (FV3), the best-studied member of the Iridoviridae family, as our model system. The genomic sequence of FV3 revealed a gene, 75L that has striking homology to LITAF. 75L is an 84 amino acid protein that has sequence identity with the C-terminus of cellular LITAF, but lacks the N-terminus of LITAF. Because of the similarities between 75L and LITAF, we hypothesize that 75L interferes with LITAF's function. Specifically, we propose that 75L functions in a dominant negative fashion, antagonizing cellular LITAF function by mediating interactions through the C-terminal half of LITAF but lacking the N-terminal binding sites of LITAF. Since the role of LITAF is unknown, our research into the function of this unique cellular gene will help explain the neurodegenerative disease that is associated with mutations in LITAF, as well as advancing viral pathogenesis. Finally, the studies here will help understand how FV3 causes disease and may help management of viral outbreaks in natural populations.

该提案中概述的研究旨在使用科学上未开发但经济上重要的病毒家族，即虹彩病毒科，以确定新型病毒-宿主相互作用基因，这将有助于确定以前未识别的细胞抗病毒途径。我们选择研究虹彩病毒科中的病毒-宿主相互作用是出于多种原因。 首先，与疱疹病毒科和痘病毒科不同，对虹彩病毒科的生物学缺乏重要的基础研究。其次，通过检查新的病毒家族，可以识别出针对未表征的宿主抗病毒策略的新基因。 最后，许多虹彩病毒科已被证实是鱼类和野生动物严重疾病的病原体，影响水产养殖和野生动物保护。为了了解虹彩病毒科家族如何规避宿主防御，我们选择蛙病毒3（FV 3），虹彩病毒科家族中研究得最好的成员，作为我们的模型系统。 FV 3的基因组序列揭示了一个基因，75 L，与LITAF具有惊人的同源性。 75 L是一种84个氨基酸的蛋白质，其与细胞LITAF的C-末端具有序列同一性，但缺乏LITAF的N-末端。 由于75 L和LITAF之间的相似性，我们假设75 L干扰LITAF的功能。具体来说，我们提出，75 L功能的显性负的方式，拮抗细胞LITAF功能介导的相互作用，通过C-末端的一半LITAF，但缺乏N-末端的LITAF结合位点。由于LITAF的作用尚不清楚，我们对这种独特细胞基因功能的研究将有助于解释与LITAF突变相关的神经退行性疾病，以及推进病毒发病机制。 最后，这里的研究将有助于了解FV 3如何引起疾病，并可能有助于管理自然人群中的病毒爆发。