Division of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London, W2 1PG, UK; E-mail:
Viruses. 2009 Dec;1(3):780-801. doi: 10.3390/v1030780. Epub 2009 Nov 6.
Since its initial description as an HIV-1 integrase (IN) interactor seven years ago, LEDGF has become one of the best-characterized host factors involved in viral replication. Results of intensive studies in several laboratories indicated that the protein serves as a targeting factor for the lentiviral DNA integration machinery, and accounts for the characteristic preference of Lentivirus to integrate within active transcription units. The IN-LEDGF interaction has been put forward as a promising target for antiretroviral drug development and as a potential tool to improve safety of lentiviral vectors for use in gene therapy. Additionally, as a natural ligand of lentiviral IN proteins, LEDGF has been successfully used in structural biology studies of retroviral DNA integration. This review focuses on the structural aspects of the IN-LEDGF interaction and their functional consequences.
自七年前最初被描述为 HIV-1 整合酶 (IN) 相互作用因子以来,LEDGF 已成为涉及病毒复制的研究最透彻的宿主因子之一。几家实验室的深入研究结果表明,该蛋白作为慢病毒 DNA 整合机制的靶向因子,并且解释了慢病毒在转录活跃单元内整合的特征偏好。IN-LEDGF 相互作用已被提出作为抗逆转录病毒药物开发的有前途的靶标,并且作为提高用于基因治疗的慢病毒载体安全性的潜在工具。此外,作为慢病毒 IN 蛋白的天然配体,LEDGF 已成功用于逆转录病毒 DNA 整合的结构生物学研究。本文综述了 IN-LEDGF 相互作用的结构方面及其功能后果。