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Thymidine kinase activity of biochemically transformed mouse cells after superinfection by thymidine kinase-negative, temperature-sensitive, herpes simplex virus mutants

1978; Elsevier BV; Volume: 85; Issue: 2 Linguagem: Inglês

10.1016/0042-6822(78)90452-x

1096-0341

Saul Kit, D. R. Dubbs, P A Schaffer,

Virus-based gene therapy research

Previous studies have shown that thymidine kinase (TK)-negative mutants isolated from HSV-1 clone 101, HSV-2 (333), marmoset herpesvirus, and pseudorabies virus enhanced the resident TK activity of biochemically transformed mouse fibroblast [LM(TK−)/HSV-1 Cl 7] cells. The present study shows that 10 additional TK-negative HSV-1 mutants isolated from HSV-1 strains HF and KOS also stimulated the resident TK activity of LM(TK−)/HSV-1 Cl 7 cells. To identify possible HSV-1 gene(s) regulating the formation of the resident HSV-1 TK, the LM(TK−)/HSV-1 Cl 7 cells were superinfected at permissive (34.5°) and nonpermissive (39°) temperatures with TK-negative mutants that were also temperature-sensitive (ts) for virus replication. TK-negative, HSV-1 ts mutants from 12 complementation groups (tsA1, B2, C4, E6, F18, G3, J12, K13, M19, N20, O22, and ts-24) were studied. All of these TK-negative HSV-1 ts mutants enhanced the resident TK activity of LM(TK−)/HSV-1 Cl 7 cells at the permissive temperature, and all mutants, except HSV-1 ts B2, did so when infections were carried out at the nonpermissive temperature. The resident TK activity of LM(TK−)/HSV-1 Cl 7 cells was either unaffected, or it was depressed after infection at 39° by mutant ts B2 at multiplicities of infection of 3–25 PFU/cell. The experiments indicate that the product of HSV-1 gene B is one of the regulatory proteins required for TK enhancement in biochemically transformed cells.