ISOLATION AND CHARACTERIZATION OF A HEAT-INDUCIBLE SIMIAN-VIRUS 40 MUTANT

A new type of temperature-sensitive mutant of SV-40 that is capable of productive infection in permissive cells but not of maintenance of viral DNA integration in transformed cells at the conditional temperature was isolated. Virus development is induced when cells transformed by this mutant are shifted to temperatures above 39.degree. C, but it is not induced below this temperature. The plaque-purified, temperature-sensitive mutant virus confers heat inducibility to new host cells, indicating that the conditional function is a property of the viral genome. Unlike previously described temperature-sensitive SV-40 mutants, in(ts)-1501 is capable of productive infection in permissive cells at the conditional temperature. The morphology, growth and oncogenicity of in(ts)-1501-transformed cells at 37.degree. C are similar to those of cell lines transformed by wild-type SV-40. HK10-c2(in(ts)-1501), a cloned cell line, transformed at 37.degree. C by the mutant virus, exhibits a transient increase in DNA synthesis before cell death at the conditional temperature. Many properties of in(ts)-1501 are analogous to those of the heat-inducible mutants of bacteriophages in which a heat-inactivated protein is responsible for the stable integration of the prophage in the bacterial chromosome. [Hamster kidney, African green monkey kidney, human embryonic lung and hamster tumor cells were used.].