Effects of deletions on expression of the herpes simplex virus thymidine kinase gene from the intact viral genome: the amino terminus of the enzyme is dispensable for catalytic activity

We have transferred two deletions affecting the 5' end of the herpes simplex virus thymidine kinase (TK) gene into the intact viral genome. One, extending from -12 to +189, had no effect on TK mRNA synthesis and only a small effect on TK activity, although the first 27 codons of the TK polypeptide were deleted. The other, extending from -85 to +85, severely impaired TK mRNA synthesis. We conclude that the amino terminus of the TK polypeptide is dispensable for catalytic activity, and that expression of TK in viral infections requires some of the same promoter elements used in uninfected cells.

[1]  M. Halpern,et al.  Positive control of the herpes simplex virus thymidine kinase gene requires upstream DNA sequences , 1983, Journal of virology.

[2]  H. Marsden,et al.  Processing of herpes simplex virus proteins and evidence that translation of thymidine kinase mRNA is initiated at three separate AUG codons , 1983, Journal of virology.

[3]  S. McKnight,et al.  Transcriptional control signals of a eukaryotic protein-coding gene. , 1982, Science.

[4]  James M. Roberts,et al.  Gene amplification and gene correction in somatic cells , 1982, Cell.

[5]  D. Zipser,et al.  Mapping functional domains in the promoter region of the herpes thymidine kinase gene. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[6]  R. Axel,et al.  Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: Identification of an upstream control region , 1981, Cell.

[7]  J. Smiley,et al.  Construction of a double-jointed herpes simplex viral DNA molecule: inverted repeats are required for segment inversion, and direct repeats promote deletions. , 1981, Virology.

[8]  D. McGeoch,et al.  Identification and mapping of two polypeptides encoded within the herpes simplex virus type 1 thymidine kinase gene sequences , 1981, Journal of virology.

[9]  W. Summers,et al.  Nucleotide sequence of the thymidine kinase gene of herpes simplex virus type 1. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Mackem,et al.  Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. , 1981, Cell.

[11]  S. McKnight The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. , 1980, Nucleic acids research.

[12]  S. McKnight,et al.  Expression of the herpes thymidine kinase gene in Xenopus laevis oocytes: an assay for the study of deletion mutants constructed in vitro. , 1980, Nucleic acids research.

[13]  S. Mackem,et al.  Regulation of herpesvirus macromolecular synthesis: transcription-initiation sites and domains of alpha genes. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Dimock,et al.  Herpes simplex virus thymidine kinase transcripts are absent from both nucleus and cytoplasm during infection in the presence of cycloheximide , 1980, Journal of virology.

[15]  J. Smiley Construction in vitro and rescue of a thymidine kinase-deficient deletion mutation of herpes simplex virus , 1980, Nature.

[16]  R. Watson,et al.  A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis , 1980, Nature.

[17]  W. Gilbert,et al.  Sequencing end-labeled DNA with base-specific chemical cleavages. , 1980, Methods in enzymology.

[18]  R. F. Weaver,et al.  Mapping of RNA by a modification of the Berk-Sharp procedure: the 5' termini of 15 S beta-globin mRNA precursor and mature 10 s beta-globin mRNA have identical map coordinates. , 1979, Nucleic acids research.

[19]  C. Preston Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK , 1979, Journal of virology.

[20]  R. Watson,et al.  Characterization of transcription-deficient temperature-sensitive mutants of herpes simplex virus type 1. , 1978, Virology.

[21]  W. Leung Evidence for a herpes simplex virus-specific factor controlling the transcription of deoxypyrimidine kinase , 1978, Journal of virology.

[22]  P. Sharp,et al.  Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids , 1977, Cell.

[23]  Richard Axel,et al.  Transfer of purified herpes virus thymidine kinase gene to cultured mouse cells , 1977, Cell.

[24]  D. R. Dubbs,et al.  Regulation of herpesvirus thymidine kinase activity in LM(TK) cells transformed by ultraviolet light-irradiated herpes simplex virus. , 1977, Virology.

[25]  R. Buttyan,et al.  Herpes simplex virus gene expression in transformed cells. I. Regulation of the viral thymidine kinase gene in transformed L cells by products of superinfecting virus , 1976, Journal of virology.

[26]  E. Southern Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[27]  Shie-Sheng Lin,et al.  Expression of the Viral Thymidine Kinase Gene in Herpes Simplex Virus-Transformed L Cells , 1974, Journal of virology.

[28]  B. Roizman,et al.  Regulation of Herpesvirus Macromolecular Synthesis I. Cascade Regulation of the Synthesis of Three Groups of Viral Proteins , 1974, Journal of virology.

[29]  B. Mcauslan,et al.  Regulation of herpes simplex virus-induced thymidine kinase. , 1974, Biochemical and biophysical research communications.