Functional characterization of structural protein V of bovine adenovirus-3

牛腺病毒3结构蛋白V的功能表征

• 批准号: RGPIN-2019-06661
• 负责人: Tikoo, Suresh
• 金额: $ 3.64万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739035
• 关键词: Functional; characterization; structural; protein; bovine

Production of mature bovine adenovirus-3 (BAdV-3) virions require double stranded viral DNA and viral proteins (non-structural and structural). The non-structural viral proteins are expressed during early\late times post infection but do not form the part of mature infectious progeny visions. Most of the structural proteins are produced at late times post infection and are part of the mature infectious progeny visions. Of these, protein V is a structural proteins which appears to be involved in ribosome biogenesis and in maintaining the integrity of viral capsid for the production of progeny BAdV-3. We believe that involvement of BAdV-3 protein V in the production of mature infectious progeny virions may require protein-protein interactions. In fact, our initial experiments suggest that BAdV-3 protein V may interact with viral (IVa2) and cellular (nucleoli and DDX21) proteins. The overall goal is to confirm and characterize these protein-protein interactions, and elucidate the role these interactions may play in different functions of protein V.The goal will be achieved by a) confirming and characterizing the interaction of protein V with viral protein IVa2, b) confirming and characterizing the interaction of BAdV-3 protein V with cellular proteins nucleolin and DDX21, c) mapping the domains of i) protein V interacting with IVa2, nucleoli and DDX21, ii) IVa2, nucleoli and DDX21 interacting with protein V, d) determining the biological significance of of these interactions in the production of mature infectious progeny visions by constructing and evaluating recombinant bovine adenovirus-3 expressing mutant (interacting domain deleted\substituted) protein V. The results of this study will help us in understanding and elucidating the functions of these interactions in the production of mature infectious progeny BAdV-3. Since protein V is Mastadenovirus genus specific protein, the findings of the proposed research will not only help in further elucidation and advancing the knowledge on BAdV-3 biology, but also about other members of Mastadenovirus genus. In addition, the research findings may pave way for developing and evaluating improved BAdV-3 based vaccine delivery vehicles for animal vaccination. Thus, both academicians (teaching\research) and animal health industry including producer groups will be benefited.

成熟的牛腺病毒-3 （badv3）病毒粒子的产生需要双链病毒DNA和病毒蛋白（非结构和结构）。非结构病毒蛋白在感染后的早期和晚期表达，但不形成成熟的感染性子代视觉的一部分。大多数结构蛋白是在感染后后期产生的，是成熟的感染性子代视觉的一部分。其中，蛋白V是一种结构蛋白，似乎参与核糖体的生物发生，并维持病毒衣壳的完整性，以产生子代badv3。我们认为badv3蛋白V参与成熟感染性子代病毒粒子的产生可能需要蛋白-蛋白相互作用。事实上，我们的初步实验表明，badv3蛋白V可能与病毒（IVa2）和细胞（核仁和DDX21）蛋白相互作用。我们的总体目标是确认和表征这些蛋白-蛋白相互作用，并阐明这些相互作用在蛋白V的不同功能中可能发挥的作用。我们将通过a)确认和表征蛋白V与病毒蛋白IVa2的相互作用，b)确认和表征badv3蛋白V与细胞蛋白核蛋白和DDX21的相互作用，c)绘制蛋白V与IVa2、核核和DDX21相互作用的结构域，ii) IVa2，d)通过构建和评价表达突变体（相互作用结构域缺失\取代）蛋白V的重组牛腺病毒-3，确定这些相互作用在成熟感染性子代产生中的生物学意义。本研究结果将有助于我们理解和阐明这些相互作用在成熟感染性子代产生中的功能。由于蛋白V是乳腺病毒属特异性蛋白，本研究结果不仅有助于进一步阐明badv3的生物学特性，而且有助于进一步了解乳腺病毒属的其他成员。此外，该研究结果可能为开发和评估改进的基于badv3的动物疫苗递送载体铺平道路。因此，无论是院士（教学/研究）还是动物保健产业（包括生产者团体）都将受益。