Mechanisms of oncogenesis by subgroup F avian leukosis viruses

Abstract

Subgroup F avian leukosis viruses, such as RAV-61 and ring-necked pheasant virus, are recombinants between exogenous chicken retroviruses and endogenous pheasant viruses and contain new envelope (env) genes. Chickens infected as 10-day-old embryos with subgroup F viruses develop fibrosarcomas, nephroblastomas, osteopetrosis, B-cell lymphomas, and a high incidence of a proliferative disorder involving the lung. Fibrosarcomas, nephroblastomas, and lymphomas appear after long latent periods (3 to 12 months). They contain discrete virus-cell junction fragments and are therefore clonal outgrowths of a single infected cell. Two ring-necked pheasant virus-induced B-cell lymphomas and an adenocarcinoma of the abdomen contained proviruses integrated at the c-myc locus and elevated levels of myc mRNA. At least four of the fibrosarcomas appeared to contain proviruses integrated at a common site, suggesting that a specific cellular gene may be involved in these tumors. The host gene has not been identified, however; 16 different oncogene probes failed to hybridize to fibrosarcoma junction fragments. In contrast to these neoplasms, lung lesions appeared rapidly (4 to 5 weeks), showed no evidence of clonality, and lacked long terminal repeat-initiated transcripts other than viral 35S and 21S mRNA. We conclude, therefore, that subgroup F retroviruses induce the proliferative disorder of the lung by a different mechanism.