Sela-Donenfeld D, Korner M, Pick M, Eldor A, Panet A
Department of Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Virology. 1996 Sep 1;223(1):233-7. doi: 10.1006/viro.1996.0472.
Hemangiomas are localized tumors of vascular cells which appear frequently in humans and animals, and their mode of induction is unknown. Recently, a new field strain of avian retrovirus, avian hemangioma virus (AHV), was isolated from spontaneous hemangiomas in layer hens. Sequence analysis of the AHV genome revealed the presence of three prototypic retroviral genes, gag, pol, and env, but no oncogenes. AHV was capable of inducing hemangiomas in hens in vivo, but it induced a strong cytopathic effect in cultured endothelial cells. The AHV envelope glycoprotein, gp85, was found to be responsible for the cell-killing effect. Four independent lines of experimental evidence indicated that AHV induces a cytopathic effect through a typical programmed cell death, apoptosis: (i) morphological changes in cells visualized by light microscopy, (ii) nuclear condensation and fragmentation indicated by 4',6-diamidino-2- phenylindole staining, (iii) intranucleosomal degradation of DNA demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining, and (iv) flow cytometry analysis of the DNA content of the infected cells. Quiescent endothelial G0/G1 cells were much more sensitive to AHV-induced apoptosis than actively dividing cells, suggesting that the AHV ability to induce apoptosis is dependent on the proliferative state of the infected cells.
血管瘤是血管细胞的局部肿瘤，在人类和动物中经常出现，其诱发方式尚不清楚。最近，从蛋鸡的自发性血管瘤中分离出一种新的禽逆转录病毒野外株，即禽血管瘤病毒（AHV）。对AHV基因组的序列分析显示存在三个典型的逆转录病毒基因，即gag、pol和env，但没有癌基因。AHV能够在体内诱导母鸡产生血管瘤，但在培养的内皮细胞中会诱导强烈的细胞病变效应。发现AHV包膜糖蛋白gp85是造成细胞杀伤效应的原因。四条独立的实验证据表明，AHV通过典型的程序性细胞死亡即凋亡来诱导细胞病变效应：（i）通过光学显微镜观察到的细胞形态变化，（ii）4',6-二脒基-2-苯基吲哚染色显示的核浓缩和碎片化，（iii）末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记染色证明的DNA核小体内降解，以及（iv）对感染细胞DNA含量的流式细胞术分析。静止的内皮G0/G1期细胞比活跃分裂的细胞对AHV诱导的凋亡敏感得多，这表明AHV诱导凋亡的能力取决于被感染细胞的增殖状态。
