Characterization and susceptibility to antiviral agents of herpes simplex virus type 1 containing a unique thymidine kinase gene with an amber codon between the first and the second initiation codons

Arch Virol. 2008;153(2):303-14. doi: 10.1007/s00705-007-1096-9. Epub 2007 Dec 10.


A herpes simplex virus type 1 (HSV-1) containing a thymidine (TK) gene with an amber mutation at the 8th position counted from the first AUG codon was isolated from a child with acute gingivostomatitis. The virus was predicted to express a mutant viral translated from the 2nd AUG codon at the 46th amino acid position and consisting of 331 amino acids. The virus was as sensitive to acyclovir (ACV), 5-bromovinyl-2'-deoxyuridine (BVdU), 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), and 1-beta-D-arabinofuranosylthymine (araT) as a wild-type HSV-1. The mutant TK showed the same level of TK activity as the wild-type TK at reaction temperatures of 34 degrees C, 37 degrees C and 39 degrees C. ACV, BVdU, BVaraU, and araT inhibited the replication of the TK-deficient and drug-resistant HSV-1 and HSV-2 in 293T cells in which the mutant TK was expressed to the same extent as in cells in which intact HSV-1-TK was expressed, whereas BVdU and BVaraU inhibited the replication of these viruses less strongly in cells in which HSV-2-TK was expressed. It can be concluded that the mutant HSV-1 exists in nature as a variant and possesses the necessary phosphorylation activities to form ACV-monophosphate from ACV, to form BVdU-diphosphate through BVdU-monophosphate from BVdU, and to form BVaraU-diphosphate through BVaraU-monophosphate from BVaraU. These results indicate that the mutant HSV-1-TK with a deletion of the first 45 amino acid residues is phenotypically the same as that of wild-type HSV-1-TK in terms of the phosphorylation activity of TK-associated anti-herpes virus drugs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Base Sequence
  • Cell Line
  • Child
  • Codon, Terminator / genetics*
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / genetics*
  • Herpesvirus 1, Human / isolation & purification
  • Herpesvirus 2, Human / drug effects
  • Herpesvirus 2, Human / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Sequence Deletion
  • Stomatitis, Herpetic / virology
  • Temperature
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / metabolism
  • Viral Plaque Assay
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism
  • Virus Replication / drug effects


  • Antiviral Agents
  • Codon, Terminator
  • Viral Proteins
  • Thymidine Kinase