Transformation by rat-derived oncogenic retroviruses.

Abstract

Retroviruses are reverse transcriptase-containing infectious agents which replicate through a deoxyribonucleic acid (DNA) copy of their genomic ribonucleic acid (RNA) (44). During the past decade, our understanding of the genetic structure and life cycle of retroviruses has increased rapidly due in large measure to the development of quantitative cell culture assays for retroviruses and the discovery of the enzymatic machinery involved in the viral replicative cycle. The discovery of reverse transcriptase (1, 45) removed a major intellectual barrier to our understanding of RNA tumor viruses and provided a rational approach for applying conventional techniques of molecular biology to the study of how these agents transform specific target cells.The most intriguing biological aspect of retrovirology has been the diverse array of oncogenic retroviruses that has been discovered. Most isolates of retroviruses replicate in cell cultures and animals without causing any obvious pathogenic effects. On the other hand, highly oncogenic retroviruses have been isolated from several vertebrates. Approximately 10 to 20 of these highly oncogenic variants have been isolated, and reviews have been written recently categorizing the viruses and discussing their biology and molecular structure (3,18,35,48). Each of these viruses can cause abnormal growth of various target cells in cell culture, and in some cases a good correlation exists between the pathological effects of the virus in cell culture and the oncogenicity of the virus in its susceptible vertebrate hosts.During the past 8 to 9 years, my laboratory has been studying one particular group of these highly oncogenic viruses isolated from rats. Three different isolates of highly oncogenic retroviruses have been isolated from rats. The first isolate was described in 1964 by Harvey, in the course of her studies with mouse-derived Moloney leukemia virus (Mo-MuLV) (7,20). Inoculation of Mo-MuLV into mice results in overt thymic leukemia in infected animals. In early studies, investigators routinely maintained their leukemogenic stocks by passage of these viruses from mouse to mouse. In the course of such t Review based on the Eli Lilly & Co. Award Lecture given at the 1980 American Society for Microbiology Annual Meeting. animal passage, Harvey inoculated rats with Mo-MuLV, and these animals also developed thymic leukemia. However, in the course of such rat passage of Mo-MuLV, Harvey noted that the disease syndrome changed when the rat-passaged virus was reinoculated into mice. Instead of causing thymic leukemia after a relatively long latent period, the virus induced the rapid onset of fibrosarcomas and an erythroid leukemia with splenomegaly. The etiological agent that was responsible for the new disease syndrome was named Harvey sarcoma virus (Ha-SV), and this agent was subsequently biologically cloned. In 1967, a second isolate of a highly oncogenic virus was isolated from rats. Kirsten (22, 23) inoculated another mouse leukemia-inducing virus into Wistar Furth rats and noted ...

Deletions of specific regions of the simian sarcoma-associated virus genome are found in defective viruses and in the simian sarcoma virus

“…in the identification of similar murine leukemia virus sequences in each viral genome (18). Rous sarcoma virus mutants defective in pol are also associated preferentially with an env deletion (5).…”