Import of Adenovirus DNA into the nucleus

超出提供的空间。腺病毒是一种无包膜的DNA病毒，基因组为-36kb。在人类中，腺病毒会导致大量的胃肠道和呼吸道感染。它们也是病毒性结膜炎的主要原因，包括流行性角膜结膜炎(EKC)，这是一种威胁长期视觉功能的疾病，目前还没有有效的治疗方法。此外，腺病毒由于具有广泛的组织嗜性，正作为人类基因治疗的载体被广泛研究。虽然对腺病毒如何穿透细胞到达细胞质已经有了很大的了解，但对腺病毒基因组核导入的分子机制知之甚少，这是病毒复制的关键。这项建议旨在获得对腺病毒DNA导入的详细分子洞察力。其目的是：1)研究腺病毒与核孔复合体的对接机制，重点分析腺病毒六邻体蛋白及其与特定核孔蛋白的相互作用。2)将分析蛋白VII在腺病毒DNA通过核孔复合体运输中的作用，并将研究蛋白VII作为一种实现有效基因转移的非病毒方法的可能性。3)分析了包括hsc70及其辅助因子在内的胞浆因子在病毒毛孔复合体脱壳和DNA导入中的作用。综合考虑，这项工作将为理解致病DNA病毒基因组的核输入提供一个有价值的模型。这项工作还可以促进人类EKC新疗法的开发。最后，为开发有效的非病毒基因转移方法提供了基础，这将有助于基因治疗和细胞功能研究。表演网站========================================Section End===========================================

EXCEED THE SPACE PROVIDED. Adenoviruses are non-enveloped DNA viruses with an -36 kb genome. In humans, adenoviruses cause a significant number of gastrointestinal and respiratory infections. They also are a major cause of viral conjunctivitis including epidemic keratoconjunctivitis (EKC), a condition that can threaten long-term visual function and for which there is no effective treatment. In addition, adenoviruses are being intensively investigated as vectors for human gene therapy because of their broad tissue tropism. Although significant insight has been obtained on how adenovirus penetrates the cell to reach the cytoplasm, little is known about the molecular mechanism of nuclear import of the adenovirus genome, which is critical for virus reproduction. This proposal is directed at obtaining detailed molecular insight on adenovirus DNA import. The aims are: 1) The mechanism for docking of adenovirus to the nuclear pore complex will be investigated, focusing on an analysis of the adenovirus hexon protein and its interaction with specific nucleoporins. 2) The role of protein VII in the transport of adenovirus DNA through the nuclear pore complex will be analyzed, and the possibility that protein VII can be used as a nonviral method for achieving efficient gene transfer will be investigated. 3) The role of cytosolic factors, including hsc70 and its cofactors, in virus uncoating at the pore complex and in DNA import will be analyzed. Considered together, this work will provide a valuable model for understanding the nuclear import of the genomes of pathogenic DNA viruses. The work also could potentiate the development of new therapies for EKC in humans. Finally, it could provide the basis for developing efficient means for nonviral gene transfer, which would be useful for gene therapy and functional studies of cells. PERFORMANCE SITE ========================================Section End===========================================