Nuclear imiport of baculovirus

为了传播感染，许多病毒在宿主细胞的细胞核中复制，并且必须将它们的基因组运输到细胞核中。此外，病毒载体——包含感兴趣的基因——也必须进入细胞核，以允许基因表达。今天，病毒复制和细胞进入的许多方面在分子水平上得到了很好的理解；然而，人们对病毒如何将其遗传物质传递到细胞核中知之甚少。详细描述病毒基因组的细胞核输入是抗病毒治疗发展的重要一步，抗病毒治疗可能通过阻断病毒基因组进入感染细胞的细胞核来成功解决病毒性疾病。我的研究项目主要是研究蛋白质和病毒进入和离开细胞核的机制。杆状病毒是节肢动物特有的DNA病毒，在宿主细胞的细胞核内进行复制。杆状病毒已被成功地用于控制害虫，也被广泛地用作昆虫细胞中多种重组蛋白的真核表达系统。此外，杆状病毒能够转导哺乳动物细胞而不产生病毒复制或细胞病变效应，这使得杆状病毒成为用于基因治疗的潜在非人类病毒DNA载体。尽管杆状病毒在农业、研究和医学方面具有明显的重要性，但杆状病毒生命周期的许多方面仍未被确定。其中一个方面是杆状病毒将其基因组传递到细胞核的机制。本研究计划的主要目的是描述杆状病毒基因组进入细胞核之前和之后的一系列事件。在这些研究中，我们将使用杆状病毒科的原型加利福尼亚亲笔多核多角体病毒（AcMNPV）。我们还将研究新组装的杆状病毒核衣壳离开细胞核的机制。这项研究的发现可能会导致对大分子进出细胞核的运输机制的各种见解，以及设计更有效的基因治疗载体的程序。

In order to spread infection, many viruses replicate in the nucleus of their host cells and must transport their genome into the nucleus. In addition, viral vectors - containing a gene of interest - must also enter the cell's nucleus, to allow for gene expression. Today, many aspects of viral replication and cell entry are well understood at the molecular level; however, very little is known about how viruses deliver their genetic material into the nucleus. A detailed characterization of the nuclear import of viral genomes is an important step in the development of anti-viral therapy that may successfully resolve viral diseases by interrupting entry of the viral genome into the nucleus of infected cells. My research program focuses on study of the mechanism by which proteins and viruses enter and exit the cell nucleus. This proposal deals with the study of the nuclear transport of baculoviruses, which are arthropod-specific DNA viruses that replicate in the nucleus of their host cells. Baculoviruses have successfully been used to control pests, and are also used extensively as a eukaryotic expression system for the production of numerous recombinant proteins in insect cells. Moreover, their ability to transduce mammalian cells without either viral replication or a cytopathic effect makes the baculovirus a potential non-human viral DNA vector for use in gene therapy. Despite the obvious importance of baculoviruses for agricultural, research and medical purposes, many aspects of the baculovirus life cycle remain uncharacterized. One such aspect is the mechanism by which the baculovirus delivers its genome into the cell nucleus. The main objective of this research proposal is to delineate a series of events preceding and following the import of the baculovirus genome into the nucleus. For these studies, we will use Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the archetype of the Baculoviridae family. We will also examine the mechanism by which the new assembled baculovirus' nucleocapsid exits the nucleus. Findings from this study may lead to various insights into the mechanism involved in transporting large macromolecules into and out of the nucleus, as well as procedures to design more efficient vectors for gene therapy.