An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer

An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer
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一系列鼠白血病病毒相关元件在逆转录病毒基因转移的灵长类受体中传播和表达

DOI:
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发表时间:
1996
影响因子:
5.4
通讯作者:
Malcolma . Martin
Malcolma . Martin
中科院分区:
医学2区
文献类型:
--
作者:
D. Purcell;Christine Broscius;E. Vanin;C. Buckler;A. Nienhuis;Malcolma . Martin

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在基因转移实验中,对恒河猴发生的T细胞淋巴瘤进行了直接的RNA-PCR分析,发现存在几种不同的重组小鼠白血病病毒(MuLV)。最突出的是预期的MuLV重组,命名为MoLTRAmPhoenv,其中辅助包装病毒的两性包膜与Moloney MuLV衍生载体的长末端重复序列(LTR)连接。这种逆转录病毒在自然界中并不存在。从载体LTR获得的一个额外的核心增强子副本可能已经增强了MoLTRAmPhoenv MuLV在几种不同类型的恒河猴细胞中的复制特性,与原型两性小鼠MuLV4070A相比。出乎意料的是,至少两种形成水貂细胞焦点的MuLV元件,来自小鼠包装细胞系中表达的内源性逆转录病毒序列,也被传播并在其中一只猕猴中高表达。此外,在猕猴淋巴瘤中检测到类似小鼠病毒的VL-30序列,但这些序列没有转录成RNA。在灵长类基因转移受体中意外地出现了一系列与MuLV相关的结构,这要求对产生逆转录病毒载体的包装细胞中是否存在可传播的逆转录病毒元件和具有改变的趋向性或生长特性的复制能力病毒进行始终保持警惕的检查。
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.
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