Purcell D F, Broscius C M, Vanin E F, Buckler C E, Nienhuis A W, Martin M A
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Virol. 1996 Feb;70(2):887-97. doi: 10.1128/JVI.70.2.887-897.1996.
Direct RNA-PCR analyses of T-cell lymphomas that developed in rhesus macaques during a gene transfer experiment revealed the presence of several different recombinant murine leukemia viruses (MuLV). Most prominent was the expected MuLV recombinant, designated MoLTRAmphoenv in which the amphotropic env of the helper packaging virus was joined to the long terminal repeat (LTR) of the Moloney MuLV-derived vector. This retrovirus does not exist in nature. An additional copy of the core enhancer acquired from the vector LTR may have augmented the replicative properties of MoLTRAmphoenv MuLV in several different rhesus cell types compared with the prototype amphotropic MuLV4070A. Unexpectedly, at least two types of mink cell focus-forming MuLV elements, arising from endogenous retroviral sequences expressed in the murine packaging cell line, were also transmitted and highly expressed in one of the macaques. Furthermore, murine virus-like VL-30 sequences were detected in the rhesus lymphomas, but these were not transcribed into RNA. The unanticipated presence of an array of MuLV-related structures in a primate gene transfer recipient demands ever-vigilant scrutiny for the existence of transmissible retroviral elements and replication-competent viruses possessing altered tropic or growth properties in packaging cells producing retroviral vectors.
在一项基因转移实验中,对恒河猴体内发生的T细胞淋巴瘤进行直接RNA-PCR分析,结果显示存在几种不同的重组鼠白血病病毒(MuLV)。最显著的是预期的MuLV重组体,命名为MoLTRAmphoenv,其中辅助包装病毒的嗜异性env与莫洛尼MuLV衍生载体的长末端重复序列(LTR)相连。这种逆转录病毒在自然界中不存在。与原型嗜异性MuLV4070A相比,从载体LTR获得的核心增强子的额外拷贝可能增强了MoLTRAmphoenv MuLV在几种不同恒河猴细胞类型中的复制特性。出乎意料的是,至少两种源自鼠包装细胞系中表达的内源性逆转录病毒序列的貂细胞集落形成MuLV元件,也在其中一只猕猴体内传播并高度表达。此外,在恒河猴淋巴瘤中检测到鼠类病毒样VL-30序列,但这些序列未转录成RNA。在灵长类基因转移受体中意外出现一系列与MuLV相关的结构,这就要求对生产逆转录病毒载体的包装细胞中是否存在具有改变的嗜性或生长特性的可传播逆转录病毒元件和具有复制能力的病毒进行始终保持警惕的审查。