Molecular analysis of baculovirus regulatory factors involved in viral gene expression, replication, and assembly

杆状病毒是节肢动物特有的大型 DNA 病毒。 它们已被开发为环境可持续的昆虫控制剂、非常成功的蛋白质表达载体，最近还被开发为人类基因治疗载体。 它们也是研究真核基因调控和病毒复制机制的优秀模型系统。杆状病毒含有编码许多基因的大型基因组，并且需要基因组的协调表达才能使这些病毒感染并杀死细胞。 病毒基因的正确表达需要关键病毒调控基因的作用，这些基因是病毒基因表达的主要协调者，也是病毒 DNA 复制所必需的。 这项研究的主要目的是了解病毒调节蛋白如何在分子水平上发挥作用。调节蛋白的正确表达对于确保正常感染至关重要，其活性与病毒毒力和宿主范围直接相关。 这项研究还研究了产生病毒形式所需的基因，这种病毒会导致患病昆虫的感染从一个组织传播到另一个组织。人们对杆状病毒如何从受感染的细胞中逸出知之甚少，但我们正在分子水平上表征病毒蛋白，这些蛋白可能涉及与细胞结构相互作用以促进病毒传播。 从这些关于病毒如何感染和杀死细胞的研究中获得的基础知识可以应用于包括人类医学在内的许多生物学领域。 此外，这些研究可能会导致改进环境可持续的昆虫控制剂，并可能增强蛋白质表达和基因治疗载体。

Baculoviruses are large DNA viruses that are specific for arthropods. They have been developed as environmentally sustainable insect control agents, highly successful protein expression vectors and more recently as human gene therapy vectors. They are also excellent model systems for the investigation of eukaryotic gene regulation and mechanisms of viral replication. Baculoviruses contain large genomes that code for many genes and a coordinated expression of the genome is needed to enable these viruses to infect and kill cells. Correct expression of the viral genes requires the action of pivotal viral regulatory genes which are the primary coordinators of viral gene expression and are also required for viral DNA replication. The primary objectives of this study are to understand how viral regulatory proteins work at the molecular level. Correct expression of regulatory proteins is essential to ensure a normal infection and their activities are directly related to viral virulence and host range. This study is also investigating genes specifically required for production of the form of virus which causes spread of an infection from tissue to tissue in diseased insects. Very little is known about how baculoviruses get out of infected cells but we are characterizing at a molecular level viral proteins that may be involved interacting with the cellular structures to facilitate viral transmission. The fundamental knowledge obtained form these studies on how viruses infect and kill cells can be applied to many areas of biology including human medicine. In addition, these investigations could lead to improved environmentally sustainable insect control agents and potentially enhanced protein expression and gene therapy vectors.