INFECTION of fibroblasts by avian sarcoma virus (ASV) leads to neoplastic transformation of the host cell. Genetic analyses have implicated specific viral genes in the transforming process1–4, and recent results suggest that a single viral gene is responsible4. Normal chicken cells contain DNA homologous to part of the ASV genome5–8; moreover, embryonic fibroblasts from certain strains of chickens can produce low titres of infectious type C viruses either spontaneously9 or in response to various inducing agents10. None of the viruses obtained from normal chicken cells, however, can transform fibroblasts, and results with molecular hybridisation indicate that the nucleotide sequences responsible for transformation by ASV are not part of the genetic complement of the normal cell11. We demonstrate here that the DNA of normal chicken cells contains nucleotide sequences closely related to at least a portion of the transforming gene(s) of ASV; in addition, we have found that similar sequences are widely distributed among DNA of avian species and that they have diverged roughly according to phylogenetic distances among the species. Our data are relevant to current hypotheses of the origin of the genomes of RNA tumour viruses12 and the potential role of these genomes in oncogenesis13.

DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA

Recombination occurs at a high rate in retroviral replication, and its observation requires a virion containing two different RNA molecules (heterodimeric particles). Analysis of retroviral recombinants formed after a single round of replication revealed that (i) the nonselected markers changed more frequently than expected from the rate of recombination of selected markers; (ii) the transfer of the initially synthesized minus strand strong stop DNA was either intramolecular or intermolecular; (iii) the transfer of the first synthesized plus strand strong stop DNA was always intramolecular; and (iv) there was a strong correlation between the type of transfer of the minus strand strong stop DNA and the number of template switches observed. These data suggest that retroviral recombination is ordered and occurs during the synthesis of both minus and plus strand DNA.

https://science.sciencemag.org/content/sci/250/4985/1227.full.pdf

Retroviral recombination and reverse transcription.

Cells of embryos of the high leukemic mouse strain AKR can be grown in culture as virus-negative cell lines However, these lines and clonal sublines uniformly have the capacity to initiate synthesis of murine leukemia virus Exposure of the cells to 5-iododeoxyuridine or 5-bromodeoxyuridine induced synthesis of virus in as high as 01 to 05 percent of the cells; many of the cells were producing virus as soon as 3 days after initiation of treatment Induction of virus by these drugs is several orders of magnitude greater than that obtained with any other treatment tested These studies indicate that the full genome of murine leukemia virus is present in an unexpressed form in all AKR cells and provide a potentially powerful technique for activating leukemia virus genomes in other cell systems

http://science.sciencemag.org/content/sci/174/4005/155.full.pdf

Murine Leukemia Virus: High-Frequency Activation in vitro by 5-Iododeoxyuridine and 5-Bromodeoxyuridine

Introduction. The study of the molecular biology of retroviruses has revealed a number of features not found in other groups of viruses. In recent years, a large number of excellent reviews of the field have appeared (Table 1). In writing this article, it is not my intention to cover ground already well treated in review form. Instead, I will consider only a limited number of interrelated subjects dealing with the organization of information in tumour virus genomes and its transfer from parent to progeny. In general, I will ignore primary data and present only the inferred structures and mechanisms and point out experimental approaches that might fill in gaps in our knowledge. Retroviruses form a large and diverse group, with isolates from many different vertebrates. In most cases, our knowledge of the molecular biology of the viruses is derived from one model system, the avian sarcoma-leukosis viruses (ASV).

Robin A. Weiss

Papers

Induction of avian tumor viruses in normal cells by physical and chemical carcinogens.

Genetic recombinants and heterozygotes derived from endogenous and exogenous avian RNA tumor viruses

Host gene control of endogenous avian leukosis virus production.

Cell transformation induced by Rous sarcoma virus: analysis of density dependence.