Chatis P A, Holland C A, Hartley J W, Rowe W P, Hopkins N
Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408-11. doi: 10.1073/pnas.80.14.4408.
To probe the genetic basis of disease specificity of nondefective murine type C viruses, we are constructing recombinants in vitro between molecular clones of Friend murine leukemia virus (Fr-MuLV) and Moloney murine leukemia virus (Mo-MuLV). Fr-MuLV induces erythroleukemias when injected into newborn NFS mice, whereas Mo-MuLV almost invariably induces T-cell lymphomas. We find that a recombinant whose genome is derived primarily from Fr-MuLV but which has 621 nucleotides of Mo-MuLV information at its 3' end induces almost exclusively thymic lymphomas. The sequences derived from Mo-MuLV include 99 nucleotides encoding the carboxyl terminus of Prp15E, the origin of DNA +-strand synthesis, all of the U3 region, and 36 nucleotides of the R portion of the long terminal repeat. When the segment of Mo-MuLV was removed and replaced with the comparable segment from Fr-MuLV, the virus was again erythroblastosis-inducing. These results, in conjunction with studies from other laboratories [Laimins, L. A., Khoury, G., Gorman, C., Howard, B. & Gruss, P. (1982) Proc. Natl. Acad. Sci. USA 79, 6453-6457], suggest that transcriptional signals in U3 may determine tissue tropism and hence influence disease specificity ("targeting") of murine leukemia viruses.
为了探究无缺陷鼠C型病毒疾病特异性的遗传基础，我们正在体外构建Friend鼠白血病病毒（Fr-MuLV）和莫洛尼鼠白血病病毒（Mo-MuLV）分子克隆之间的重组体。将Fr-MuLV注入新生NFS小鼠时会诱发红白血病，而Mo-MuLV几乎总是诱发T细胞淋巴瘤。我们发现，一种重组体，其基因组主要源自Fr-MuLV，但在其3'端有621个核苷酸的Mo-MuLV信息，几乎只诱发胸腺淋巴瘤。源自Mo-MuLV的序列包括编码Prp15E羧基末端的99个核苷酸、DNA正链合成起点、整个U3区域以及长末端重复序列R部分的36个核苷酸。当去除Mo-MuLV的片段并用Fr-MuLV的相应片段替换时，该病毒又能诱发成红细胞增多症。这些结果，连同其他实验室的研究[莱明斯，L.A.，库里，G.，戈尔曼，C.，霍华德，B. & 格鲁斯，P.（1982年）美国国家科学院院刊79，6453 - 6457]表明，U3中的转录信号可能决定组织嗜性，从而影响鼠白血病病毒的疾病特异性（“靶向性”）。
