Avian hemangioma retrovirus induces cell proliferation via the envelope (env) gene

Several years ago, a field strain retrovirus, avian hemangioma Virus (AHV), was isolated from hemangioma tumors in layer hens. Sequence analysis indic ated that the AHV genome contains the three prototypic retroviral genes, ga g, pol, and env, and is devoid of an oncogene. In cultured endothelial cell s, however, AHV induced a significant cytopathic effect through a typical a poptotic cascade. We now demonstrate that AHV also induces cell proliferati on and anchorage-independent growth of BSC-1 epithelial cells and NIH-3T3 f ibroblasts. This was shown by measurements of (1) cell viability, (2) DNA s ynthesis, (3) flow cytometry analysis of the cell DNA content, and (4) clon ogenic efficiency of the infected cells. Anchorage-independent cell growth was demonstrated by colony formation in soft agar. Moreover, the AHV env ge ne was cloned into a MuLV-based retroviral vector, and infection of NIH-3T3 cells with this vector induced cell proliferation as well as clonogenic gr owth. These results suggest that AHV, which is devoid of an oncogene, is a pleiotropic activator capable of inducing either apoptosis or cellular prol iferation, depending on the infected cell type, (C) 2000 Academic Press.