Mutants of murine leukemia viruses and retroviral replication.
Mutants of murine leukemia viruses and retroviral replication.
复制标题
鼠白血病病毒突变体和逆转录病毒复制。
DOI：
10.1016/0304-419x(87)90001-1
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Lobel,LI
中科院分区：
文献类型：
--
作者：
Goff,SP;Lobel,LI
鼠白血病病毒构成了一个具有复制能力的逆转录病毒大家族，在自然界中广泛分布。这些病毒是最早被发现会在实验动物中引起肿瘤的生物制剂之一，并且在三十多年来一直是深入研究的主题（有关评论，请参阅参考文献 1、2）。这些病毒获取宿主基因的能力以及快速诱导肿瘤的能力，对于识别所谓的癌基因（与引发多种肿瘤密切相关的序列）发挥了重要作用。这些年来，人们对逆转录病毒的兴趣一直很浓厚，但近年来，由于人类基因组中相关序列的存在[3]，以及导致人类疾病的相关病毒的发现，人们对逆转录病毒的兴趣大大增加[4]。另一个新的兴趣焦点是使用小鼠病毒作为基因转移载体。许多携带外源基因的构建体都是基于具有复制能力的鼠病毒的基因组，并且使用此类载体进行基因转移的效率已经得到明确记录[5-7]。这些研究激发了近期有关病毒复制的大部分工作。逆转录病毒的生命周期在 RNA 病毒中是独一无二的，我们对其复制的了解大部分都是基于对鼠白血病病毒的研究。几种鼠白血病病毒分离株正在深入研究中，它们的遗传结构和复制都非常相似。其基因组已得到最详细表征的病毒是莫洛尼鼠白血病病毒，它与肉瘤病毒复合分离[8]；这是第一个获得完整基因组核苷酸序列的病毒[9]。该家族的其他成员包括 Rauscher 鼠白血病病毒、Kirsten 鼠白血病病毒、Friend 鼠白血病病毒以及几乎相同的一对 Gross 鼠白血病病毒和 AKV 病毒。这些分离株中的每一种都会在受感染的动物中引起独特的疾病，并且对培养的细胞没有严重影响。它们在感染细胞培养物后不会转化细胞，也不会在感染动物后立即引起肿瘤。相反，受感染的细胞成为子代病毒的永久生产者，没有明显的不良影响。经过长时间的潜伏期后，这些病毒确实会引起白血病。人们对疾病的诱发机制以及特定病毒转化特定细胞类型的特异性知之甚少。显然，在疾病过程中，新病毒通常通过与内源性小鼠序列重组而产生。在某些情况下，人们发现肿瘤携带与内源性癌基因相邻的原病毒。但其他事件对于疾病的诱发很可能是必要的（甚至是充分的）。我们关于鼠白血病病毒 (MuLV) 的大部分信息历来是通过感染过程的生化分析而不是遗传分析获得的。因此，病毒粒子中存在的基因产物是用血清学试剂来定义的；事实上，编码主要病毒体蛋白的基因（gag 基因）之所以被命名，是因为它编码的蛋白质首先被识别为群体特异性抗原。病毒基因组复制所需的主要基因产物逆转录酶，通过体外测定的 DNA 聚合酶的酶活性来鉴定。同样，病毒基因组复制的细节是通过核酸杂交实验确定的。因此，病毒生命周期的大致轮廓是通过遗传学或突变体分析的微小贡献来确定的。最近……
The murine leukemia viruses constitute a large family of replication-competent retroviruses that are widely distributed in nature. These viruses were among the first biological agents that were found to cause tumors in experimental animals, and have been the subject of intensive study for more than three decades (for reviews, see Refs. 1, 2). The abifity of these viruses to acquire host genes, and with them the capacity for rapid tumor induction, has been instrumental in the identification of the so-called oncogenes, sequences strongly imphcated in initiating a wide variety of tumors. Interest in retroviruses has been strong throughout these years, but has increased enormously in recent years because of the presence of related sequences in the human genome [3], and the discovery of related viruses that cause disease in man [4]. Another new focus of interest has been the use of the mouse viruses as vectors for gene transfer. Numerous constructs which carry foreign genes have been based on the genome of the replication-competent murine viruses, and the efficiency of gene transfer with such vectors has already been clearly documented [5-7]. These studies have motivated much of the recent work on the replication of the viruses. The retroviral life cycle is unique among the RNA viruses, and much of what we know about their replication is based on studies of the murine leukemia viruses. Several isolates of murine leukemia viruses are under intensive study, all very similar in their genetic structure and replication. The virus whose genome has been characterized in the most detail is Moloney murine leukemia virus, isolated in complex with a sarcoma virus [8]; this was the first virus for which a complete genomic nucleotide sequence was obtained [9]. Other members of this family include the Rauscher murine leukemia virus, the Kirsten murine leukemia virus, the Friend murine leukemia virus, and the nearly identical pair, Gross murine leukemia and AKV viruses. Each of these isolates causes a distinctive disease in infected animals, and have no serious effects on cells in culture. They do not transform cells following infection of cell culture, nor do they cause tumors immediately following infection of animals. Instead, infected cells become permanent producers of progeny virus with no apparent ill effects. After long latency periods these viruses do cause leukemia; the mechanism of the induction of the disease, and the specificity of a given virus for transformation of particular cell types, are poorly understood. It is clear that during the course of the disease, new viruses art often generated by recombination with endogenous mouse sequences. In some cases, it has been found that tumors carried proviruses adjacent to an endogenous oncogene; but other events may well be necessary (or even sufficient) for the induction of disease. The bulk of our information about the murine leukemia viruses (MuLVs) was historically obtained by biochemical analyses of the infection process rather than by genetic analyses. Thus, the gene products present in virions were defined with serological reagents; in fact the gene encoding the major virion protein, the gag gene, was named because it encodes proteins first identified as group-specific antigens. The major gene product required for replication of the viral genome, reverse transcriptase, was identified by its enzymatic activity as a DNA polymerase as assayed in vitro. Similarly, the details of the replication of the viral genome were determined by nucleic acid hybridization experiments. Thus, the broad outlines of the viral life cycle were determined with only minor contributions from genetics or the analysis of mutants.More recently …