For the ICRF Annual Report, 1979: II. Retroviruses as Mutagens: Isolation of Revertants with Deletions and/or Insertions in
the ASV Provirus in B31 Cells after Superinfection with MuLV
Varmus here provided an overview of his research during his sabbatical year at the Imperial Cancer Research Fund in London
in 1978-79. His studies focused on the ways in which retroviruses cause mutations of genes, including the genes deposited
by other retroviruses that had previously infected the cell.
Item is a photocopy.
Number of Image Pages:
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Original Repository: University of California, San Francisco. Archives and Special Collections. Harold E. Varmus Papers
Reproduced with permission of the Regents of the University of California.
Medical Subject Headings (MeSH):
Avian Sarcoma Viruses
Retroviruses and the Genetic Origins of Cancer, 1970-1993
Letter from Harold Varmus to Howard Young, National Cancer Institute (August 28, 1979)
For the ICRF Annual Report, 1979: I. The Rare Revertants of an ASV-Transformed Rat Cell Have Lost Proviral DNA or Bear Mutations
in SRC (1979)
For the ICRF Annual Report, 1979: III. Co-Transfection with Papovavirus and Retrovirus DNA Using Recombinant DNA Prepared
In vitro (1979)
The DNA of retroviruses can integrate into many sites in the genomes of their host cells, suggesting that retroviruses might
be able to cause mutations by disruption of genes, in the manner demonstrated for Mu-1 bacteriophage and transposable elements
of procaryotes. I have tested this possibility by asking whether a non-transforming retrovirus can insert its DNA into a
previously-established, transforming provirus and thus inactivate its biological effects. For these experiments, I used selective
techniques to obtain revertants of the ASV-transformed rat-1 line B31 following infection at high multiplicity with the Moloney
strain of murine leukemia virus. Most of the ca. 35 revertants isolated from the MuLV-infected B31 cells belong to the two
classes of spontaneous revertants characterized previously (loss of proviral D9A or mutations in src; see above), but a few
exhibited curious lesions in the single ASV provirus present in B31 cells.
ASV proviruses can be denoted "Cell DNA-3'5'-gag-pol-env-src-3'5'-Cell DNA". "3'5'"
is a repeated sequence of 300 nucleotide pairs composed of sequences from both ends of viral RNA; the viral genes are written
from left to right in their order from the 5' to 3' ends of viral RNA. All of the observed lesions involved regions
of provirus less than 1500 nucleotides from the left hand end. In one case, approximately l0^6 daltons of the left end of
the provirus was deleted, and 5-6x10^6 daltons of new DNA was inserted. In the second case, no deletion was evident by restriction
mapping, but an insert of 5-6x10^6 daltons was located about 500 bases from the left end of the provirus. In the third case,
no insertion was identified, but ca. 1.1x10^6 daltons of DNA, including the left end of the provirus and flanking cellular
DNA, was deleted. Studies in collaboration with N. Quintrell (University of California, San Francisco) have demonstrated
that these lesions interfere with the transcription of the ASV provirus, including the src gene, by either removing or interrupting
signals for synthesis and/or processing of viral RNA.
I am now attempting to define the nature of the insertions end the boundaries of the deletions in these three cases and to
explore the significance of the localization of these lesions to the left end of the ASV provirus.