Virus-host interactions in frog virus 3

青蛙病毒3中病毒与宿主的相互作用

• 批准号: RGPIN-2020-04843
• 负责人: Brunetti, Craig
• 金额: $ 3.1万
• 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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717434
• 关键词: Virus; host; interactions; frog; virus

Background: The overarching goal of my research program is to explore virus-host interactions in frog virus 3 (FV3), a member of the Ranavirus genus of the Iridoviridae family. Ranaviruses are of concern because of their impact on amphibian communities. Amphibian populations are globally threatened with 43% of amphibians demonstrating population declines. One factor contributing to amphibian declines are Ranaviruses. Our lab has been studying FV3 to understand the basic biology of the virus, as well as characterizing how FV3 impacts amphibian populations. To understand mechanisms of pathogenesis and innate immune defenses our lab will explore two parallel ways in which viruses interact with a host cell. One area of investigation explores virus-host protein-protein interactions, the other area studies defences based on small signalling molecules. Hypothesis: We hypothesize that the FV3 gene 97R and cytokinin hormones modulate host defense mechanisms in the cell. Specifically, we will identify and characterize binding partners of FV3 97R. We will also determine what role cytokinins play in vertebrate viral infections. To achieve these goals, we propose to: 1) Establish the role that prohibitin-1 plays during FV3 infections. We demonstrated that the FV3 gene 97R binds to prohibitin-1. We will determine whether the 97R/prohibitin-1 interaction plays a biological role in an FV3 infection, perhaps modulating the cell death pathways in the cell. 2) Ascertain whether endogenous cytokinins are altered in viral infections. Cytokinins are hormones that carry out a variety of roles in plants. We will explore whether an FV3 infection alters the production of cytokinin's by the host cell and if so, what biological pathways are involved. 3) Determine if exogenous cytokinins inhibit viral infections. We have shown that cytokinin's can inhibit an FV3 infection. We propose to determine what stage of the FV3 replication cycle is inhibited as well as determining the full complement of cytokinin's that inhibit FV3 replication. Significance: The research outlined in this proposal is aimed at using a scientifically unexploited but economically important virus family, the Iridoviridae, to explore novel anti-viral strategies, provide new insight into the function of the host immune system, and understand how virus-host interactions lead to viral pathogenesis. This proposal focuses on FV3 97R and its interactions with prohibitin-1, which may shed light on a novel virus-host interaction. In addition, although cytokinin hormones are well documented in plants, their roles in vertebrate systems remain largely unknown. Characterizing cytokinins in vertebrates will provide a better understanding of basic biology and may reveal an uncharacterized host defense mechanism. Ultimately, these studies will help understand how FV3 causes disease and may help management of viral outbreaks in natural populations.

背景：我的研究计划的主要目标是探索青蛙病毒3(FV3)的病毒与宿主的相互作用，FV3是虹彩病毒科RANA病毒属的成员。拉纳病毒之所以令人担忧，是因为它们对两栖动物群落的影响。两栖动物种群在全球范围内受到威胁，43%的两栖动物种群数量出现下降。导致两栖动物数量下降的一个因素是拉纳病毒。我们的实验室一直在研究FV3，以了解病毒的基本生物学，以及FV3如何影响两栖动物种群。为了了解发病机制和先天免疫防御机制，我们的实验室将探索病毒与宿主细胞相互作用的两种平行方式。一个研究领域探索病毒-宿主蛋白-蛋白质相互作用，另一个领域研究基于小信号分子的防御。 假设：我们假设FV3基因97R和细胞分裂素激素调节细胞内的宿主防御机制。具体来说，我们将确定和表征FV3 97R的结合伙伴。我们还将确定细胞分裂素在脊椎动物病毒感染中扮演的角色。为达致这些目标，我们建议： 1)确定Bhibitin-1在FV3感染过程中的作用。我们证明了FV3基因97R与Prohibitin-1结合。我们将确定97R/Prohibitin-1相互作用是否在FV3感染中发挥生物学作用，可能调节细胞中的细胞死亡途径。 2)确定内源性细胞分裂素在病毒感染中是否发生改变。细胞分裂素是一种在植物中发挥各种作用的荷尔蒙。我们将探索FV3感染是否改变了宿主细胞产生的细胞分裂素，如果是，涉及哪些生物学途径。 3)确定外源性细胞分裂素是否抑制病毒感染。我们已经证明，细胞分裂素可以抑制FV3感染。我们建议确定FV3复制周期的哪个阶段被抑制，以及确定抑制FV3复制的细胞分裂素的完整补充。 意义：本建议中概述的研究旨在利用科学上未开发但具有重要经济意义的虹彩病毒科病毒家族来探索新的抗病毒策略，为宿主免疫系统的功能提供新的见解，并了解病毒与宿主的相互作用如何导致病毒致病。本研究的重点是FV3 97R及其与Prohibitin-1的相互作用，这可能有助于揭示一种新的病毒-宿主相互作用。此外，尽管细胞分裂素激素在植物中有很好的文献记载，但它们在脊椎动物系统中的作用在很大程度上仍不清楚。脊椎动物细胞分裂素的特征将有助于更好地理解基础生物学，并可能揭示一种尚未确定的宿主防御机制。最终，这些研究将有助于理解FV3是如何导致疾病的，并可能有助于管理自然人群中的病毒爆发。