The early history of tumor virology: Rous, RIF, and RAV.
- Harry Rubin
- Proceedings of the National Academy of Sciences…
The development of in vitro (tissue culture) assay systems for murine leukemia (MuLV)l" 2 and sarcoma (MSV)3-7 viruses, the demonstration of the defectiveness of the MSV genome,3 and its rescue with various MuLV's7 have brought out certain remarkable similarities between these viruses and those of the avian leukosisRous sarcoma complex.3' 7, 8, "a Subsequent studies of the murine viruses, which I propose to outline briefly in this presentation, not only emphasize further the extent and significance of these similarities, but show also that the natural behavior, prevalence, and modes of spread of murine leukemia and sarcoma viruses follow very closely the patterns of the known avian tumor viruses. Avian Tumor Viruses.-During the many intervening years since Rous's discovery of the Rous sarcoma virus (RSV) in 1911, much information has been obtained concerning the nature and behavior of the RNA tumor viruses. However, as is true of all virus research, the modern era of RNA tumor virus research can be said to begin with the development of in vitro test systems. Manaker and Groupe reported altered foci in chick embryo cultures induced by RSV, following which Rubin developed a tissue culture test for the growth and assay of avian leukosis viruses (ALV).9' ga In reporting the resistance-inducing factor (RIF) test, Rubin showed that ALV interfered with the focus-forming activity of PSV in chick embryo fibroblast (CEF) cultures.10 Arined with two simplified and reproducible assay procedures, the focus-forming for RSV and the RIF for ALV, Rubin, Hanafusa, Vogt, and others demonstrated the defectiveness of the Bryan strain of Rous sarcoma virus,iOa 11 described its rescue in vitro with various leukosis viruses,12 and defined to a considerable extent the natural history and immunological specificities of the latter in infected chicken populations."3 13a Subsequently my associates and I reported complement-fixing (CF) antigens in hamster tumors induced by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). Using sera of tumored hamsters, we showed that these antigens were also present in chicken sarcomas and in chick embryo cells infected with avian leukosis viruses. The CF antigens were not sedimented with virus particles and appeared to be soluble internal antigenic components shared by all the known avian leukemia-sarcoma viruses.'4' 15 This latter finding provided the basis for the development of the COFAL test (complement fixation for avian leukosis),' a test now widelv used for detection and assay of ALV infections in chickens. These observations stimulated further studies on the nature of the internal antigens as structural components of the leukosis viruses;17 on their presence in "nonproducer" avian and hamster sarcoma cells;'8-20 and on the transfer of the noninfectious RSV genome from sarcoma cells to normal cells by direct contact.21 22 As a result of these studies it was soon established that ALV and RSV were similar to the influenza-like myxoviruses in that they contained anl internal group-specific antigen in addition to the outer envelope aiitigeim which had been shown earlier to be the determinant of serotype specificity. 12 This broad sharing of soluble virion antigens made it possible with the use of the COFAL test to detect, identify, and