Graf T, Beug H, Hayman M J
Proc Natl Acad Sci U S A. 1980 Jan;77(1):389-93. doi: 10.1073/pnas.77.1.389.
Defective avian leukemia viruses of the avian erythroblastosis (AEV), avian myelocytomatosis (MC29), and avian myeloblastosis (AMV) type induce the proliferation of leukemic cells with properties of erythroblasts, macrophages, and myeloblasts, respectively. Their target cells can be separated and have properties of cells of the erythroid (AEV) and myeloid lineage (MC29 and AMV), respectively. In the present study we have shown that this target cell specificity is not due to the ability of the different strains to infect only certain types of hematopoietic cells. Instead, AEV was found to replicate in macrophages and to induce the expression of p75 AEV, its presumptive transforming protein. Likewise, MC29 was found to replicate in AEV-infected erythroblasts as well as in AMV-infected myeloblasts and to express the p110 MC29 protein in these cells. Superinfection with MC29 or AMV of ts34 AEV-infected erythroblasts did not impair their capacity to accumulate hemoglobin after shift to nonpermissive temperature. Our results support a model in which the transforming proteins of AEV, MC29, and MAV block the differentiation of their target cells by competitively inhibiting the action of a hypothetical homologous cellular differentiation protein synthesized in the corresponding target cells only.
禽成红细胞增多症(AEV)、禽骨髓细胞瘤病(MC29)和禽成髓细胞瘤(AMV)类型的缺陷型禽白血病病毒分别诱导具有成红细胞、巨噬细胞和成髓细胞特性的白血病细胞增殖。它们的靶细胞可以分离,分别具有红系(AEV)和髓系(MC29和AMV)细胞的特性。在本研究中,我们表明这种靶细胞特异性并非由于不同毒株仅感染某些类型造血细胞的能力。相反,发现AEV可在巨噬细胞中复制并诱导其假定的转化蛋白p75 AEV的表达。同样,发现MC29可在感染AEV的成红细胞以及感染AMV的成髓细胞中复制,并在这些细胞中表达p110 MC29蛋白。ts34 AEV感染的成红细胞用MC29或AMV进行超感染后,在转移至非允许温度后积累血红蛋白的能力并未受损。我们的结果支持一种模型,即AEV、MC29和MAV的转化蛋白通过竞争性抑制仅在相应靶细胞中合成的一种假定的同源细胞分化蛋白的作用来阻断其靶细胞的分化。