Thymidine kinase genes and the induction of anti-viral responses by interferon.

A mouse fibroblast cell-line deficient in thymidine kinase (Ltk(-) aprt(-)) fails to show an anti-viral response when treated with interferon. After introduction of a viral tk gene into these cells the resultant clones showed normal responses to interferon. However, one such tk-containing clone (C6) spontaneously lost its ability to respond to interferon by inducing an antiviral state although it retained its ability to induce the enzyme oligo(2'-5' A)-synthetase. This sub-clone (6A) still expressed thymidine kinase activity but restriction endonuclease analysis indicated an alteration in the sequences flanking the exogenous viral tk gene. Our results suggest that a modification in the exogenous viral DNA sequences led to a loss of interferon sensitivity.