Characterization of a temperature-sensitive mutant of polyoma virus

A mutant of polyoma virus (TS-a) which is temperature sensitive in both its plaque-forming and transforming abilities at the nonpermissive temperature of 38.5 °, but not at the permissive temperature of 31.5 ° has been further characterized. TS-a was found to be inhibited in its ability to produce infectious virus in mouse cells at 38.5 °; this inhibition could be overcome by infection with high multiplicites. The ratio of the yield of TS-a to the yield of wild-type polyoma increases from 10⁻³ to almost unity when the input multiplicity varies from 0.1 to 100 PFU/cell.The temperature sensitivity of TS-a is due not to an increased heat lability of the structural components (capsid protein and DNA) of the completed virus particles, but to an increased heat sensitivity of some intracellular process in viral development. This temperature-sensitive process has been found to take place after uncoating of the infecting virus particle, occurring at the time of, and being required for, the production of virus-sized DNA; the “induction” of host cell DNA synthesis is not markedly inhibited in TS-a infected resting mouse kidney cells at 38.5 °. This finding implies that the virus must contribute some other function (s) besides causing the “induction” of host cell DNA synthesis for neoplastic transformation to occur (i.e., stimulation of host cell DNA synthesis by itself is not enough to cause transformation).Some of the possible temperature-sensitive processes that could be concerned with both the production of viral DNA and transformation are discussed.