Ishimoto A, Takimoto M, Adachi A, Kakuyama M, Kato S, Kakimi K, Fukuoka K, Ogiu T, Matsuyama M
J Virol. 1987 Jun;61(6):1861-6. doi: 10.1128/JVI.61.6.1861-1866.1987.
Despite the high degree of homology (91%) between the nucleotide sequences of the Friend-mink cell focus-forming (MCF) and the Moloney murine leukemia virus (MuLV) genomic long terminal repeats (LTRs), the pathogenicities determined by the LTR sequences of the two viruses are quite different. Friend-MCF MuLV is an erythroid leukemia virus, and Moloney MuLV is a lymphoid leukemia virus. To map the LTR sequences responsible for the different disease specificities, we constructed nine viruses with LTRs recombinant between the Friend-MCF and Moloney MuLVs. Analysis of the leukemia induced with the recombinant viruses showed that a 195-base-pair nucleotide sequence, including a 75-base-pair nucleotide Moloney enhancer, is responsible for the tissue-specific leukemogenicity of Moloney MuLV. However, not only the enhancer but also its downstream sequences appear to be necessary. The Moloney virus enhancer and its downstream sequence exerted a dominant effect over that of the Friend-MCF virus, but the enhancer sequence alone did not. The results that three of the nine recombinant viruses induced both erythroid and lymphoid leukemias supported the hypothesis that multiple viral genetic determinants control both the ability to cause leukemia and the type of leukemia induced.
尽管弗瑞德-貂细胞集落形成病毒(MCF)与莫洛尼鼠白血病病毒(MuLV)基因组的长末端重复序列(LTR)的核苷酸序列之间具有高度同源性(91%),但这两种病毒由LTR序列所决定的致病性却大不相同。弗瑞德-MCF MuLV是一种红白血病病毒,而莫洛尼MuLV是一种淋巴细胞白血病病毒。为了定位负责不同疾病特异性的LTR序列,我们构建了9种病毒,其LTR是弗瑞德-MCF和莫洛尼MuLV之间的重组体。对重组病毒诱导的白血病的分析表明,一个195个碱基对的核苷酸序列,包括一个75个碱基对的莫洛尼增强子,决定了莫洛尼MuLV的组织特异性致白血病性。然而,不仅增强子,其下游序列似乎也是必需的。莫洛尼病毒增强子及其下游序列对弗瑞德-MCF病毒的增强子及其下游序列具有显性作用,但单独的增强子序列则不然。9种重组病毒中有3种诱导了红白血病和淋巴细胞白血病,这一结果支持了如下假说:多个病毒遗传决定因素既控制引发白血病的能力,也控制所诱导的白血病类型。