Early viral functions of in (ts)-1501 temperature-sensitive SV40 mutant

Abstract

TEMPERATURE-SENSITIVE (ts) virus mutants have been useful in defining virus–host interactions in SV40 productive and transforming infections. We have isolated an SV40 ts mutant, in(ts)-1501, by extracellular mutagenesis, using ultraviolet radiation of wild type (WT) SV40¹. The mutant, which has properties different from previously described SV40 ts mutants^2,3, is activated from its integrated state in nonpermissive transformed cells at temperatures above 39 °C and is capable of productive infection in permissive cells at elevated (conditional) temperatures¹. Many properties of the 1501 mutant are analogous to the early ts cI mutants of bacteriophages in which a heat-inactivated protein cannot maintain the stable integration of the prophage in the bacterial chromosome at elevated temperatures^4–8. This analogy suggested that maintenance of SV40 DNA integration in transformed cells requires an early viral function, that is, before the inception of viral DNA replication. Therefore we have investigated the effect of the in gene mutation on two other early virus functions—stimulation of host-cell DNA synthesis and tumour (T)-antigen synthesis.