100 years of Rous sarcoma virus

The discovery of Rous sarcoma virus, which was reported by Peyton Rous in the Journal of Experimental Medicine 100 years ago, opened the field of tumor virology. It showed that some cancers have infectious etiology, led to the discovery of oncogenes, and laid the foundation for the molecular mechanisms of carcinogenesis. Rous spent his entire research career at The Rockefeller Institute, and he was the JEM's longest serving editor. Here, we comment briefly on the life of this remarkable scientist and on the importance of his discoveries.     

Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia

PGA administered in doses up to 1000 mg orally a day did not significantly lower the serum urate concentration nor decrease the urinary urate or total oxypurine excretion in five hyperuricemic subjects. The folate was well absorbed, as reflected by marked increases in the serum and erythrocyte folate concentrations, and up to 50% of the administered folate could be recovered in the urine. There was no evidence of clinical or laboratory toxicity at these high doses of folate. PGA is a weak inhibitor of human liver xanthine oxidase in vitro, and much of its inhibitory effect is secondary to trace contamination by pterin-6-aldehyde, a potent inhibitor of the enzyme.     

Effect of ribavirin on Rous sarcoma virus transformation.

Ribavirin inhibited the expression of cellular transformation in normal rat kidney cells transformed by a temperature-sensitive mutant of rous sarcoma virus and chicken embryo fibroblasts infected with either a temperature-sensitive mutant or wild-type Rous sarcoma virus. Ribavirin also inhibited replication of the Rous sarcoma viruses in chicken embryo fibroblasts. The effect of ribavirin on cellular transformation was not permanent, as removal of the drug resulted in reversion to the transformed phenotype. The concentration of ribavirin necessary to inhibit the expression of cellular transformation was cytostatic for the cell lines used in this study.     

Selective inhibitory effect of two 2-nitronaphthofuran derivatives on growth and induction of transformation of Rous sarcoma virus-infected chicken embryo fibroblasts

Two 2-nitronaphthofuran derivatives exhibited a dose-dependent lethal effect on Rous sarcoma virus-tranformed chicken embryo fibroblasts. When they were added at time of infection, they prevented cell transformation, but not virus replication, in a dose-dependent manner. Since the two derivatives inhibited mainly the DNA sythesis, we assume that they altered some early DNA-dependent cell event required for cell transformation and not for the integration of provirus.     

Two-hit kinetics of focus formation in cells transfected with Rous sarcoma provirus

DNA was purified from an established line of SR-E-transformed quail cells and was assayed for transfection in turkey cells. Transfection events were determined from foci of transformed cells growth under agar overlay which was used to prevent the spread of the progeny virus. It was found that transfection with Rous sarcoma proviruses follows two-hit kinetics, indicating that at least two (unlinked) provirus are required to give rise to a focus of transformed cells.     

Localization with the electron microscope of p27 Rous sarcoma virus internal protein in chicken embryo fibroblasts. A time study at different stages after infection

Protein 76 (Pr76), the precursor of the so-called 'gag' protein of avian leukosarcoma viruses, has been localized in the light and electron microscope by using the immunoperoxidase technique in Rous sarcoma virus-infected chick embryo fibroblasts. The kinetics of the progression of the protein through the cell was studied at different times after infection. The protein was first found (after 8 h) on ribosomes located near the nucleus and then proceeded rapidly to the periphery of the cell. After 5-6 days, intracytoplasmic staining faded away and only the ribosomes close to the plasma membrane were stained. A possible association of a protein with the cytoskeleton is suggested.