Therwath A, Scherrer K
Int J Cancer. 1982 May 15;29(5):555-8. doi: 10.1002/ijc.2910290511.
We have previously shown that AEV infection of leukosis-free chickens provokes an erythroleukemia in the infected birds, and that the target cell for virus transformation is most likely an early pro-erythroblast comparable to the BFU-E. The virus infection correlates with a block in differentiation which was studied at a specific cellular gene level, namely that of the globin genes. In live birds, the viral transformation has been found to affect the transcriptional activity to two out of three adult globin genes and the phenotypic expression of the third. Indeed, the alpha A gene that is transcribed is silent as well, since its transcription product is fully eliminated in the nucleus following an "abortive processing". Chick bone marrow cells can also be transformed in vitro by AEV in which case the virus recruits, as targets, cells of the erythroid lineage belonging to a wider spectrum and hence in varying degrees of differentiation. In contrast to the results obtained with in vivo transformed cells, molecular hybridization with globin cDNA probes showed that in the erythroblasts transformed in vitro under tissue culture conditions all the three adult globin genes are transcriptionally active. In fact, low but detectable amounts of globin mRNA sequences are present in both the nuclear and cytoplasmic compartment of the cell prior to exposure to any chemical inducers of red cell differentiation. Judging from our present results, we may propose that AEV transformation in vitro does not shut off out only modulates the already functioning erythroid cell differentiation program.
我们之前已经表明,无白血病鸡感染禽成红细胞增多症病毒(AEV)会在受感染的禽类中引发红细胞白血病,并且病毒转化的靶细胞很可能是一种与爆式红系集落形成单位(BFU-E)相当的早期原红细胞。病毒感染与在特定细胞基因水平(即珠蛋白基因水平)研究的分化阻滞相关。在活禽中,已发现病毒转化会影响三个成年珠蛋白基因中两个的转录活性以及第三个基因的表型表达。实际上,被转录的αA基因也是沉默的,因为其转录产物在“流产加工”后在细胞核中被完全消除。鸡骨髓细胞也可在体外被AEV转化,在这种情况下,病毒将属于更广泛谱系且分化程度不同的红系细胞作为靶细胞。与体内转化细胞所获得的结果相反,用珠蛋白cDNA探针进行的分子杂交表明,在组织培养条件下体外转化的成红细胞中,所有三个成年珠蛋白基因都具有转录活性。事实上,在暴露于任何红细胞分化化学诱导剂之前,细胞的核和细胞质部分中都存在少量但可检测到的珠蛋白mRNA序列。根据我们目前的结果,我们可以提出,AEV体外转化并非关闭而是仅调节已经在起作用的红系细胞分化程序。