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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=766053
• 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.

生产成熟的牛腺病毒3型(BAdV-3)病毒粒子需要双链病毒DNA和病毒蛋白(非结构和结构)。非结构蛋白在感染后的早期和晚期表达，但不构成成熟的感染性后代视觉的一部分。大多数结构蛋白是在感染后的晚期产生的，是成熟的感染性后代视觉的一部分。其中，蛋白V是一种结构蛋白，它似乎参与了核糖体的生物发生和维持病毒衣壳的完整性，以产生后代BAdV-3。我们认为，BAdV-3蛋白V参与了成熟感染性子代病毒粒子的产生，可能需要蛋白质之间的相互作用。事实上，我们的初步实验表明，BAdV-3蛋白V可能与病毒(IVa2)和细胞(核仁和DDX21)蛋白相互作用。目的将通过a)确认和表征蛋白V与病毒蛋白IVa2的相互作用，b)确认并表征BAdV-3蛋白V与细胞蛋白核苷酸和DDX21的相互作用，c)绘制蛋白V与IVa2、核仁和DDX21相互作用的结构域，D)通过构建和鉴定表达突变(相互作用结构域缺失或替换)蛋白V的重组牛腺病毒-3来确定这些相互作用在成熟侵染后代产生中的生物学意义。本研究的结果将有助于我们理解和阐明这些相互作用在成熟侵染后代BAdV-3产生中的作用。由于蛋白V是肥大病毒属特有的蛋白，本研究的结果不仅有助于进一步阐明和加深对BAdV-3生物学的认识，也将有助于进一步了解肥大病毒属的其他成员。此外，本研究结果可能为开发和评价基于BAdV-3的改良BAdV-3动物疫苗接种载体奠定基础。因此，院士(教学\研究)和动物保健业包括生产者集团都将受益。