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Abstract:
The current state of knowledge concerning the biochemical transformation by Herpes Simplex virus (HSV) of mammalian cells lacking the enzyme thymidine kinase (TK) is reviewed. Transformation of thymidine kinase negative mouse cells (LTK-) to the TK+ phenotype by ultraviolet light-inactivated HSV preparations depends both on the irradiation dose and on the multiplicity of infection. Once stably associated with the transformed cell, the HSV thymidine kinase appears to be regulated differently than the cellular enzyme: HSV TK activity is maximal in stationary cells, whereas cellular TK activity is maximal during the S-pphase of growing cells. Furthermore, infection with an HSV TK- mutant virus leads to the induction of TK activity in HSV TK+ cells, but not in normal TK+ cells. Recent studies indicate that in addition to the TK gene, at least one other HSV gene, perhaps a structural antigen of the virion, is also transferred to TK- cells. This is consistent with the finding that a clone of HSV TK+ cells harbors approximately five copies per cell of 23 per cent of the HSV genome.
Insights
Herpes Simplex virus (HSV) can biochemically transform mammalian cells lacking thymidine kinase (TK). Transformed cells exhibit altered HSV TK regulation and may acquire additional HSV genes beyond the TK gene.
Area of Science:
- Biochemistry
- Molecular Biology
- Virology
Background:
- Mammalian cells lacking thymidine kinase (TK) can be transformed by Herpes Simplex virus (HSV).
- The transformation process and the characteristics of the transformed cells are not fully understood.
Purpose of the Study:
- To review the current knowledge on the biochemical transformation of TK-deficient mammalian cells by HSV.
- To elucidate the regulation of HSV-encoded TK in transformed cells and identify other transferred viral genes.
Main Methods:
- Review of existing literature on HSV-mediated cell transformation.
- Analysis of the dependence of transformation on UV-irradiation dose and multiplicity of infection.
- Comparison of HSV TK activity regulation with cellular TK activity in transformed cells.
- Investigation of TK induction by HSV TK- mutant viruses in different cell types.
Main Results:
- Transformation of TK-negative mouse cells (LTK-) to TK+ phenotype is dependent on UV-irradiation dose and multiplicity of infection.
- HSV TK in transformed cells shows different regulation compared to cellular TK, with maximal activity in stationary cells.
- Infection with HSV TK- mutant virus induces TK activity in HSV TK+ cells, but not in normal TK+ cells.
- Transformed cells harbor multiple copies of HSV DNA, indicating transfer of additional viral genes, potentially including a structural antigen gene.
Conclusions:
- HSV can stably transfer its TK gene and other genetic material to mammalian cells.
- The regulation of HSV TK differs from cellular TK in transformed cells.
- At least one additional HSV gene, besides the TK gene, is transferred during the transformation process.