Properties of cells carrying the herpes simplex virus type 2 thymidine kinase gene: mechanisms of reversion to a thymidine kinase-negative phenotype.

We have isolated cells with a thymidine kinase-negative (tk(-)) phenotype from cells which carry the herpes simplex virus type 2 tk gene by selection in 5-bromodeoxyuridine or 9-(2-hydroxyethoxymethyl)guanine. Both selection routines generated revertants with a frequency of 10(-3) to 10(-4), and resistance to either compound conferred simultaneous resistance to the other. tk(-) revertants fell into three classes: (i) cells that arose by deletion of all virus sequences, (ii) cells that had lost the virus tk gene but retained a nonselected virus-specific function and arose by deletion of part of the virus-specific sequence, and (iii) cells that retained the potential to express all of the virus-specific functions of the parental cells and retained all of the virus-specific DNA sequences.