Positional cloning of the mouse retrovirus restriction gene Fv1
Positional cloning of the mouse retrovirus restriction gene Fv1
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DOI：
10.1038/382826a0
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发表时间：
1996-08-29
期刊：
影响因子：
64.8
通讯作者：
Stoye, JP
中科院分区：
文献类型：
--
作者：
Best, S;LeTissier, P;Stoye, JP
脊椎动物的进化是在逆转录病毒持续感染的背景下发生的，哺乳动物基因组的大部分由内源性逆转录病毒样元件组成（1）。几个宿主基因已经进化到控制逆转录病毒复制（3），包括小鼠4号染色体上的HIV易感性1，Fv 1（参考文献3，4）。Fv 1基因在进入靶细胞后但在前病毒整合和形成前的阶段作用于鼠白血病病毒（5）。尽管限制不是绝对的，但Fv 1可预防或延迟自发性或实验诱导的病毒肿瘤（2）。在体外，Fv 1限制导致病毒滴度明显降低50- 1，000倍（6）。遗传学证据表明，Fv 1基因产物与病毒整合前复合物的一个组分（衣壳蛋白CA）之间存在直接相互作用（参考文献7-9），我们现在已经克隆了Fv 1：该基因似乎来源于与鼠白血病病毒无关的内源性逆转录病毒的gag区，这意味着尽管缺乏核苷酸序列同源性，但Fv 1蛋白及其靶mag具有功能相似性。
VERTEBRATE evolution has taken place against a background of constant retrovirus infection, and much of the mammalian genome consists of endogenous retrovirus-like elements(1). Several host genes have evolved to control retrovirus replication(3), including Friend-virus-susceptibility-1, Fv1, on mouse chromosome 4 (refs 3, 4). The Fv1 gene acts on murine leukaemia virus at a stage after entry into the target cell but before integration and formation of the provirus(5). Although restriction is not absolute, Fv1 prevents or delays spontaneous or experimentally induced viral tumours(2), In vitro, Fv1 restriction leads to an apparent 50-1,000 fold reduction in viral titre(6). Genetic evidence implicates a direct interaction between the Fv1 gene product and a component of the viral preintegration complex, the capsid protein CA (refs 7-9), We have now cloned Fv1: the gene appears to be derived from the gag region of an endogenous retrovirus unrelated to murine leukaemia virus, implying that the Fv1 protein and its target mag share functional similarities despite the absence of nucleotide-sequence homology.