Thymidine kinase gene transfer by herpes simplex virus

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.