The early history of tumor virology: Rous, RIF, and RAV.

One hundred years ago Peyton Rous recovered a virus, now known as the Rous sarcoma virus (RSV), from a chicken sarcoma, which reproduced all aspects of the tumor on injection into closely related chickens. There followed recovery of causal viruses of tumors of different morphology from 4 more of 60 chicken tumors. Subsequent studies in chickens of the biology of the first RSV isolated moved slowly for 45 y until an assay of ectodermal pocks of the chorioallantoic membrane of chicken embryos was introduced. The inadequacies of that assay were resolved with the production of transformed foci in cultures of chicken fibroblasts. There followed a productive period on the dynamics of RSV infection. An avian leukosis virus (ALV) was found in some chicken embryos and named resistance-inducing factor (RIF) because it interferes with RSV. Its epidemiology in chickens is described. Another ALV was found in stocks of RSV and called Rous-associated virus (RAV). Cells preinfected with RAV interfere with RSV infection, but RSV does not produce infectious virus unless RAV is added during or after RSV infection. Intracellular RAV provides the infectious coat for the otherwise defective RSV. The coat determines the antigenicity, host range, and maturation rate of RSV. RSV particles carry reverse transcriptase, an enzyme that converts their RNA into DNA and allows integration into the cell's DNA, where it functions as a cellular gene. This was the bridge that joined the biological era to the molecular era. Its relation to oncogenes and human cancer is discussed.

A low incidence of histiocytic sarcomatosis associated with infection of chickens with the HPRS-103 strain of subgroup J avian leukosis virus.

Ten cases of histiocytic proliferative lesions in meat-type chickens associated in low incidence with infection by subgroup J avian leukosis virus (ALV) are described. Six were field cases in adult chickens from naturally infected flocks and four were from younger birds from transmission experiments with HPRS-103 ALV or the related acutely transforming ALV strains 17 and 879. The lesions were observed mostly in the spleen and in some cases in other organs. Microscopically, the lesions were comprised mainly of pleomorphic histiocyte-like cells admixed with variable numbers of lymphoid cells. More detailed studies were carried out on two birds at 4 and 7 wk of age following infection with HPRS-103 at 1 day of age. These birds had multiple small nodular lesions in the spleen, liver, and kidney that appeared similar cytologically to the more extensive lesions in older birds. Monoclonal antibodies specific for various lymphoid and nonlymphoid accessory cells were used in immunohistochemical studies to identify a predominance of cells of monocyte/macrophage lineage, and CD4- and CD8-positive lymphocytes, in the splenic nodules. Ultrastructural studies also revealed a similar mixed population of cells. Expression of ALV group-specific antigen, and gag and ALV-J env RNA, was not a marked feature of the histiocytic lesions. The proliferative histiocytic lesion is designated a histiocytic sarcomatosis.