Fate of viral DNA in nonpermissive cells infected with simian virus 40.

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Abstract
Mouse cells are nonpermissive for SV40; replication of viral DNA is undetectable and progeny virions are not produced. Infection leads to the establishment of stably transformed cell lines in which viral DNA is covalently integrated into cellular DNA. The fate of SV40 DNA in infected mouse cells was followed to define steps in viral DNA metabolism that precede integration. A novel high MW form of SV40 DNA is synthesized shortly after infection by a process sensitive to the inhibition of DNA replication. This DNA represents polymers in which viral genomes are orgnized as tandem head-to-tail arrays. Recombination can be demonstrated with mutant viruses but the recombination frequency is not high enough to account for the synthesis of polymers by recombination between infecting genomes. Polymers apparently are synthesized by DNA replication and then recombine with one another. The polymers may also recombine with cellular DNA and are thus the precursors to integrated viral DNA. Such a model accounts for the high frequency of tandemly duplicated viral insertions in transformed cells and also leads to experimentally testable predictions.