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The AKR mouse has a high titer of murine leukemia virus early in life, and virus-negative cells derived from embryos of this mouse strain can be activated to yield murine leukemia virus by treatment with 5-iododeoxyuridine. In contrast to this high-virus strain, the NIH Swiss mouse has a low incidence of leukemia and no murine leukemia virus has been isolated from it (virus-negative). We have investigated this difference between AKR and NIH mice by examining the sequences specific for murine leukemia virus in nucleic acids of these mice. A single-stranded viral-DNA probe synthesized in vitro using murine-leukemia-virus from the AKR mouse contains at least 87% of the sequences present in the 70S viral RNA; most of these sequences are in proportions similar to their content in the 70S RNA. Using this probe in nucleic acid hybridization experiments, we have shown that NIH-mouse-cell DNA and AKR-mouse-cell DNA differ with respect to sequences specific for AKR murine-leukemia-virus: NIH-mouse-cell DNA lacks some of the virus-specific sequences present in AKR-mouse-cell DNA, and there are two distinct sets of virus-specific sequences in AKR-mouse-cell DNA, whereas there is only one set in NIH-mouse-cell DNA.RNA from virus-negative AKR-mouse cells grown in tissue culture contains some, but not all, virus-specific RNA sequences; however, within 48 hr after initiating treatment of these cells with 5-iododeoxyuridine, the complete viral genome is represented in cellular RNA.

Studies with a single-stranded DNA probe complementary to the RNA of mouse-tropic AKR murine leukemia virus indicate that the complete genome of the AKR-type murine leukemia virus is present in the DNA of high- and low-virus-yielding mouse strains, while DNA of non-virus-yielding strains contains only a part of the genome. Furthermore, in those strains where the genome is complete, two populations of virus-specific DNA sequences can be identified (more abundant and less abundant species) according to their rate of association with the probe. Low-virus-yielding mouse strains contain fewer copies of the less abundant species and, consequently, fewer complete viral genomes than do high-virus-yielding strains. Thus, in the ten strains tested, there is a good correlation between completeness of the genome of AKR-type murine leukemia virus in cellular DNA and the capacity of the cells to release infectious AKR-type murine leukemia virus. Moreover, the number of complete viral genomes correlates with the frequency of infectious virus production by virus-positive strains. DNA from wild Mus musculus also contained viral sequences, the sample tested showing reassociation kinetics identical to the non-virus-producing strains.

Poly(1-vinyluracil) and poly(9-vinyladenine), as well as the corresponding polynucleotides poly(uridylate) and poly(adenylate), inhibit acute murine leukemia virus infection in mouse-embryo cells, but they do not significantly inhibit the replication of Sindbis and vesicular stomatitis viruses. The polymers were most effective as inhibitors when added during an early stage of virus replication. Effects of vinyl polymers on the RNA-dependent DNA polymerase from the virions of murine leukemia virus were also observed.

Genetic information of murine leukemia viruses is known to be present in essentially all mice. Delineation of the biological effects of the expression of this genetic information is complicated by the difficulty in determining whether the presence of a viral antigen in a tissue is the result of gene activation that occurs independently in a large number of cells, proliferation of antigen-positive cells, or of spread of infectious virus from a few cells. This problem is further complicated by the difficulty in determining whether activation of virus genetic material is the cause or result of a biological phenomenon, such as malignancy. Further understanding of the activation of virus genes in normal cells is of great importance in answering these questions. In vitro techniques were used for the study of induction of virus. Virus-negative cell lines were established from embryos of AKR mice, which in vivo produce high titers of infectious murine leukemia virus. It was found that 5-iododeoxyuridine and 5-bromodeoxyuridine were potent inducers of virus synthesis in all clones and subclones of the AKR cells tested. In addition to establishing that the complete viral genome is a heritable component of all cells of the AKR mouse, these studies of virus activation provide novel approaches to a number of important problems in the biology of leukemia viruses.