PROGRAMMED ENDOTHELIAL-CELL DEATH INDUCED BY AN AVIAN HEMANGIOMA RETROVIRUS IS DENSITY-DEPENDENT

Hemangiomas are localized tumors of vascular cells which appear freque ntly in humans and animals, and their mode of induction is unknown. Re cently, a new field strain of avian retrovirus, avian hemangioma virus (AHV), was isolated from spontaneous hemangiomas in layer hens. Seque nce analysis of the AHV genome revealed the presence of three prototyp ic retroviral genes, gag, pol, and env, but no oncogenes. AHV was capa ble of inducing hemangiomas in hens in vivo, but it induced a strong c ytopathic effect in cultured endothelial cells. The AHV envelope glyco protein, gp85, was found to be responsible for the cell-killing effect . Four independent lines of experimental evidence indicated that AHV i nduces a cytopathic effect through a typical programmed cell death, ap optosis: (i) morphological changes in cells visualized by light micros copy, (ii) nuclear condensation and fragmentation indicated by 4',6-di amidino-2-phenylindole staining, (iii) intranucleosomal degradation of DNA demonstrated by terminal deoxynucleotidyl transferase-mediated dU TP-biotin nick end-labeling staining, and (iv) flow cytometry analysis of the DNA content of the infected cells. Quiescent endothelial G(0)/ G(1) cells were much more sensitive to AHV-induced apoptosis than acti vely dividing cells, suggesting that the AHV ability to induce apoptos is is dependent on the proliferative state of the infected cells. (C) 1996 Academic Press, Inc.