Ikeda H, Sugimura H
Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
J Virol. 1989 Dec;63(12):5405-12. doi: 10.1128/JVI.63.12.5405-5412.1989.
Fv-4 is a mouse gene which controls susceptibility to infection by ecotropic murine leukemia virus (MuLV). We previously cloned part of an endogenous MuLV associated with the resistance allele of the Fv-4 gene (Fv-4r). In this report, we describe an extended clone of the Fv-4r allele consisting of a 17-kilobase DNA fragment containing the retroviral sequence and its 5'-flanking sequence. The new DNA clone contains a truncated MuLV with delta pol-env-long terminal repeat sequences but no other MuLV-reactive sequence within 13 kilobases upstream of the truncated MuLV. Transfection of this clone into mouse cells led to transcription of Fv-4 env mRNA, expression of the Fv-4r-specific MuLV envelope protein, and resistance to infection with ecotropic MuLV but not amphotropic and dualtropic MuLVs. Restriction of ecotropic viruses appears to occur at or before viral cDNA synthesis. This result is consistent with a model of receptor interference for Fv-4 restriction. Our data also suggest that the 5' non-MuLV sequence is important for biological function, since a DNA clone which lacks most of the 5'-flanking sequence did not efficiently confer the resistance phenotype.
Fv - 4是一个小鼠基因，它控制着对亲嗜性鼠白血病病毒（MuLV）感染的易感性。我们之前克隆了与Fv - 4基因的抗性等位基因（Fv - 4r）相关的一种内源性MuLV的部分序列。在本报告中，我们描述了Fv - 4r等位基因的一个扩展克隆，它由一个17千碱基的DNA片段组成，该片段包含逆转录病毒序列及其5'侧翼序列。这个新的DNA克隆包含一个带有δ pol - env - 长末端重复序列的截短型MuLV，但在截短型MuLV上游13千碱基范围内没有其他MuLV反应性序列。将这个克隆转染到小鼠细胞中导致了Fv - 4 env mRNA的转录、Fv - 4r特异性MuLV包膜蛋白的表达，以及对亲嗜性MuLV感染的抗性，但对兼嗜性和双嗜性MuLVs没有抗性。亲嗜性病毒的限制似乎发生在病毒cDNA合成时或之前。这一结果与Fv - 4限制的受体干扰模型一致。我们的数据还表明，5'非MuLV序列对生物学功能很重要，因为一个缺少大部分5'侧翼序列的DNA克隆不能有效地赋予抗性表型。
