Nuclear imiport of baculovirus

为了传播感染，许多病毒在其宿主细胞的细胞核中复制，并且必须将其基因组运输到细胞核中。此外，病毒载体-含有感兴趣的基因-也必须进入细胞核，以允许基因表达。今天，病毒复制和进入细胞的许多方面在分子水平上都得到了很好的理解;然而，对病毒如何将其遗传物质传递到细胞核中知之甚少。病毒基因组的核输入的详细表征是开发抗病毒疗法的重要步骤，所述抗病毒疗法可通过中断病毒基因组进入受感染细胞的核而成功地解决病毒疾病。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。该提案涉及杆状病毒核转运的研究，杆状病毒是节肢动物特异性DNA病毒，在其宿主细胞的细胞核中复制。杆状病毒已成功地用于防治害虫，并且还广泛地用作在昆虫细胞中生产许多重组蛋白的真核表达系统。此外，它们在没有病毒复制或细胞病变效应的情况下感染哺乳动物细胞的能力使得杆状病毒成为用于基因治疗的潜在非人病毒DNA载体。尽管杆状病毒对于农业、研究和医学目的具有明显的重要性，但杆状病毒生命周期的许多方面仍然没有表征。一个这样的方面是杆状病毒将其基因组递送到细胞核中的机制。本研究的主要目的是描述杆状病毒基因组导入细胞核之前和之后的一系列事件。对于这些研究，我们将使用苜蓿银纹夜蛾多核型多角体病毒（AcMNPV），杆状病毒科的原型。我们还将研究新组装的杆状病毒核衣壳退出细胞核的机制。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.