Induction of an antiviral response by interferon requires thymidine kinase.
Mouse fibroblastoid cells (Ltk-) that lack thymidine kinase (tk) activity are unable to respond to murine beta-interferon by establishing antiviral activity or inducing the double-stranded RNA-dependent enzymes, oligo[(2'-5')A] polymerase and Mr 68,000 protein kinase. In contrast, the parental L-929 cell line or clonal derivatives of Ltk- cells into which the herpes virus tk gene was introduced by DNA-mediated gene transfer respond normally to interferon in developing resistance to viral infection and in inducing double-stranded RNA-dependent enzymes. Further evidence for a role of tk in the response to interferon was obtained by isolating revertants of tk+ clones that lost the herpes virus tk gene during growth in BrdUrd-containing medium. In such revertant sublines both tk enzyme activity and viral tk genes were undetectable and treatment with interferon failed to produce an antiviral effect or induce synthesis of the double-stranded RNA-dependent enzymes. Our results indicate that the ability of mouse L cells to respond to beta-interferon is dependent upon the presence of a functional tk gene. We propose that the induction of antiviral responses by interferon stringently requires a metabolite, the level of which is determined by tk activity. The system described may provide a means for elucidating the mechanisms by which responses to interferon are induced.
D000227:Adenine Nucleotides / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D005814:Genes, Viral; D007372:Interferons / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D009843:Oligoribonucleotides / Q000096:biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; C023505:2',5'-oligoadenylate; D007372:Interferons; D011494:Protein Kinases; D013937:Thymidine Kinase