Srinivasakumar N
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37235, USA.
Somat Cell Mol Genet. 2001 Nov;26(1-6):51-81. doi: 10.1023/a:1021074613196.
Human immunodeficiency virus type 1 (HIV-1) based gene transfer systems are gaining in popularity due to their ability to transduce terminally differentiated and non-dividing cells. Oncoretroviral vectors based on Moloney murine leukemia virus (MoMLV), on the other hand, can only transduce dividing cells. The reasons for increased ability of lentivirus vectors to transduce such cells has been attributed to several of the viral proteins (integrase, matrix and Vpr) that are purported to be involved in the nuclear import of the pre-integration complex (PIC). Nuclear import is also augmented by a unique triple stranded DNA region created during reverse transcription of the incoming viral RNA in the target cell (discussed in chapter 3). This chapter deals with the rationale behind the design of human immunodeficiency virus type 1 (HIV-1) based packaging systems with an emphasis on some recent advances in the field for the creation of safe and efficient HIV-1 based vectors. The review covers trans-acting proteins and cis-sequences required for the deployment of HIV-1 vectors for gene transfer. This is a rapidly advancing field that with further refinements may soon allow the utilization of HIV-1 based and/or other lentivirus vectors in a clinical setting.
基于1型人类免疫缺陷病毒（HIV-1）的基因转移系统正越来越受欢迎，因为它们能够转导终末分化细胞和非分裂细胞。另一方面，基于莫洛尼鼠白血病病毒（MoMLV）的γ-逆转录病毒载体只能转导分裂细胞。慢病毒载体转导此类细胞能力增强的原因归因于几种病毒蛋白（整合酶、基质和Vpr），据称它们参与了整合前复合物（PIC）的核输入。核输入也因在靶细胞中传入病毒RNA逆转录过程中产生的独特三链DNA区域而增强（在第3章中讨论）。本章讨论基于1型人类免疫缺陷病毒（HIV-1）的包装系统设计背后的基本原理，重点介绍该领域最近在创建安全有效的基于HIV-1的载体方面取得的一些进展。综述涵盖了用于基因转移的HIV-1载体部署所需的反式作用蛋白和顺式序列。这是一个快速发展的领域，随着进一步的改进，可能很快会允许在临床环境中使用基于HIV-1的和/或其他慢病毒载体。
