Thymidine kinaseless revertants of Ltk- cells transformed by herpes simplex virus type 1 are resistant to retransformation by homologous virus

Mouse L cells lacking thymidine kinase (Ltk-) that had been transformed to the thymidine kinase-positive (tk+) phenotype by herpes simplex virus type 1 (HSV-1) were cultured in medium containing tritiated thymidine. Six clonal lines of cells surviving this treatment were found to have the following properties: (i) the cells were tk- and had spontaneous back-reversion frequencies to the tk+ phenotype of 10(-5) or less, (ii) the cells contained HSV antigens, although in lesser amounts than in the parental transformed cells, and (iii) the cells were retransformable to the tk+ phenotype by HSV-1 at frequencies of about 1 to 13% of the frequency of the primary transformation of LtK- cells. HSV-1 plaqued as efficiently on monolayers of these cells and replicated in them to the same extent as it did in Ltk- cells. These results indicate that HSV-1-transformed L cells surviving selection with tritiated thymidine are unlike the parental Ltk- cells in that they are damaged in such a way that the cells are resistant to retransformation by homologous virus, although they remain fully permissive for virus replication.