Retroviruses: Strategies of Replication

Among the first diseases for which a viral etiology was esta­ blished were tumors, lymphomas, and sarcomas in chickens, shown by Ellermann and Bang (1908) and Rous (1910) to be transmissible with cell-free filtrates. The broad significance of these discoveries was not fully recognized at first, mainly because chickens were perceived as too distanly related to humans to provide useful and relevant models for human disease. Change came slowly. In 1936 Bittner found that a viral agent is involved in the causation of mammary cancer in mice, and in 1957 Gross discovered the first murine leukemia virus. In the years following numerous tumor-inducing viruses, infecting all classes of verte­ brates, were isolated. The decisive impulse for the development of the RNA tumor virus field sprang from advances in cell culture. In 1958 Temin and Rubin, following initial observations of Manaker and Groupe, worked out the conditions for virus-induced tumori­ genic transformation in cell culture and made this transform­ ation the basis for a quantitative assay of viral infectivity and oncogenicity. The genetic and cell biological studies that grew out of Rubin's and Temin's groundwork quickly brought into focus two puzzling problems: a requirement for DNA synthesis early in the lifecycle of the RNA tumor viruses, and the existence of genetic information in the virus that is needed for oncogenesis but not for virus reproduction.