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

Department of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, CA 94720, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2011; 108(35):14389-96. DOI: 10.1073/pnas.1108655108
Source: PubMed


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.

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Available from: Harry Rubin, Nov 15, 2015
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    • "Remarkably, it took more than 50 years from the initial report for the world to realize the magnitude of the discovery when the existence of a genetic sequence in the RVS capable of inducing transformation, the src gene was discovered. The src-encoded tyrosine kinase (TK) was the first evidence of TK activity involved in malignant transformation [3], and it was the first to demonstrate that activation occurs by phosphorylation of the aminoacid tyrosine in host cell proteins. These enzymes have been shown to be essential for the malignant transformation of cells by oncogenic signals [4]. "
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    • "These subgroups are dependent on viral envelope glycoproteins, which determine virus-serum neutralization properties, viral interference patterns, and range in infectivity in chicken and other avian cells of different phenotypes. Rubin has recently written an historical account of his early work and of studies that stemmed from it (Rubin, 2011). Epizootiology of avian leukosis virus infection. "
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