Advani S J, Weichselbaum R R, Whitley R J, Roizman B
The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Chicago, Illinois 60637, USA.
Clin Microbiol Infect. 2002 Sep;8(9):551-63. doi: 10.1046/j.1469-0691.2002.00432.x.
Herpes simplex virus-1 (HSV-1) is a relatively large double-stranded DNA virus encoding at least 89 proteins with well characterized disease pathology. An understanding of the functions of viral proteins together with the ability to genetically engineer specific viral mutants has led to the development of attenuated HSV-1 for gene therapy. This review highlights the progress in creating attenuated genetically engineered HSV-1 mutants that are either replication competent (viral non-essential gene deleted) or replication defective (viral essential gene deleted). The choice between a replication-competent or -defective virus is based on the end-goal of the therapeutic intervention. Replication-competent HSV-1 mutants have primarily been employed as antitumor oncolytic viruses, with the lytic nature of the virus harnessed to destroy tumor cells selectively. In replacement gene therapy, replication-defective viruses have been utilized as delivery vectors. The advantages of HSV-1 vectors are that they infect quiescent and dividing cells efficiently and can encode for relatively large transgenes.
单纯疱疹病毒1型（HSV-1）是一种相对较大的双链DNA病毒，可编码至少89种蛋白质，其疾病病理学特征明确。对病毒蛋白功能的了解以及对特定病毒突变体进行基因工程改造的能力，促使了用于基因治疗的减毒HSV-1的开发。本综述重点介绍了创建减毒基因工程HSV-1突变体的进展，这些突变体要么具有复制能力（病毒非必需基因缺失），要么复制缺陷（病毒必需基因缺失）。选择具有复制能力或复制缺陷的病毒取决于治疗干预的最终目标。具有复制能力的HSV-1突变体主要用作抗肿瘤溶瘤病毒，利用病毒的裂解特性选择性地破坏肿瘤细胞。在替代基因治疗中，复制缺陷病毒已被用作递送载体。HSV-1载体的优点是它们能有效感染静止和分裂细胞，并且可以编码相对较大的转基因。
