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Gene Review

UL23  -  thymidine kinase

Human herpesvirus 2

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Disease relevance of UL23

  • We also report that, in mice and rabbits in vivo, the compound is effective against both local and systemic infections with herpes simplex virus type 1, including herpetic keratitis caused by a TK- mutant which is resistant to the classical anti-herpes drugs [1].
  • CONCLUSION: Foscarnet may be an effective treatment for severe mucocutaneous disease due to acyclovir-resistant, TK-negative strains of HSV-2 [2].
  • Chicken ovalbumin gene fused to a herpes simplex virus alpha promoter and linked to a thymidine kinase gene is regulated like a viral gene [3].
  • For suicide gene therapy, VP22 activity was demonstrated under hypoxia by coupling VP22 to the HSV thymidine kinase (HSVtk) [4].
  • (iii) HSV-1(HFEM)tsB7 induced the alpha-TK gene chimeras at the nonpermissive (39 degrees C) temperature; at 39 degrees C the parental HSV-1(HFEM)tsB7 capsids accumulate at nuclear pores and do not release viral DNA [5].

High impact information on UL23


Chemical compound and disease context of UL23


Biological context of UL23

  • (Cell 24:555-565, 1981) have shown that chimeric genes constructed by fusion of 5' noncoding leader and upstream sequences of alpha genes to the 5' noncoding leader and structural sequences of the viral thymidine kinase (TK), a beta gene, are regulated as alpha genes upon recombination into the viral genome [5].
  • Sites of integration of herpes simplex virus type-2 thymidine kinase gene in human chromosomes [12].
  • Compounds with a hexamethylene spacer (18, 26b, 31) displayed the highest inhibitory values against TK-2 (IC50 = 0.3-0.5 microM) [9].
  • Contributions of thymidine kinase (TK) mutations to acyclovir (ACV) resistance were evaluated in herpes simplex virus type 1 recombinant viruses generated using a set of overlapping cosmids and plasmids [13].
  • A recurrent isolate was resistant to acyclovir and lacked thymidine kinase activity on the basis of a frameshift mutation in the thymidine kinase (tk) gene [14].

Anatomical context of UL23

  • A murine model of genital infection with a thymidine kinase-deficient (tk-) strain of herpes simplex virus type 2 (HSV-2) was utilized to examine the development of the local T cell response in the genital mucosa and draining genital lymph nodes (gLN) [15].
  • Intranasal herpes simplex virus type 2 inoculation causes a profound thymidine kinase dependent cerebral inflammatory response in the mouse hindbrain [16].
  • Following primary inoculation with attenuated thymidine kinase-deficient (TK(-)) HSV-2, B cell-deficient (microMT) mice developed a local viraemia and transient genital inflammation, suggesting a role for B cells in the innate control of local infection and inflammation [17].
  • To detect and localize a herpes simplex virus type 2 (HSV-2) thymidine kinase gene sequence in paraffin sections of brains and trigeminal ganglia of infected mice, an in situ polymerase chain reaction (ISPCR) protocol was developed [18].

Associations of UL23 with chemical compounds

  • Compound 26b competitively inhibited TK-2 with respect to thymidine and uncompetitively with respect to ATP [9].
  • N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors [9].
  • Polyamine depletion and cell cycle manipulation in combination with HSV thymidine kinase/ganciclovir cancer gene therapy [19].
  • The resistant clone was deficient in thymidine kinase (TK) activity and a nucleotide substitution, thymine for cytosine, at position 153 was identified in its TK gene [20].
  • This differs from the results for CV where only idoxuridine and bromodeoxyuridine appeared to be activated, putatively by the type II TK expressed by this virus [21].

Analytical, diagnostic and therapeutic context of UL23

  • (iv) The alpha-TK gene chimeras were not induced by infection with spontaneous TK- mutants of pseudorabies virus and bovine mammillitis virus or with human cytomegalovirus or adenovirus type 2 or by exposure to lysates of HSV-1-infected cells from which the virus was removed by centrifugation [5].
  • A polymerase chain reaction (PCR) employing primers flanking a region of the HSV thymidine kinase gene common to both HSV-1 and HSV-2 was used to detect HSV in the CSF [22].
  • We used a variety of techniques, including two-color flow cytometry and cytotoxicity assays to detect the presence of TK in the non-producing cells [23].
  • In the present studies, we demonstrate that intravaginal vaccination with an attenuated strain of this virus, which possesses a partial deletion of the thymidine kinase gene, rapidly induced durable immunity to lethal intravaginal challenge with wild-type virus [24].
  • When examined the immunofluorescence staining patterns of RXP/tk fusion proteins in transfected COS7 cells, the RXP chimeras revealed a conservation of the trafficking activity of RXP [25].


  1. A novel selective broad-spectrum anti-DNA virus agent. De Clercq, E., Holý, A., Rosenberg, I., Sakuma, T., Balzarini, J., Maudgal, P.C. Nature (1986) [Pubmed]
  2. Foscarnet therapy for severe acyclovir-resistant herpes simplex virus type-2 infections in patients with the acquired immunodeficiency syndrome (AIDS). An uncontrolled trial. Erlich, K.S., Jacobson, M.A., Koehler, J.E., Follansbee, S.E., Drennan, D.P., Gooze, L., Safrin, S., Mills, J. Ann. Intern. Med. (1989) [Pubmed]
  3. Chicken ovalbumin gene fused to a herpes simplex virus alpha promoter and linked to a thymidine kinase gene is regulated like a viral gene. Post, L.E., Norrild, B., Simpson, T., Roizman, B. Mol. Cell. Biol. (1982) [Pubmed]
  4. VP22-mediated intercellular transport for suicide gene therapy under oxic and hypoxic conditions. Greco, O., Joiner, M.C., Doleh, A., Scott, S.D. Gene Ther. (2005) [Pubmed]
  5. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. Batterson, W., Roizman, B. J. Virol. (1983) [Pubmed]
  6. Long-term presence of virus-specific plasma cells in sensory ganglia and spinal cord following intravaginal inoculation of herpes simplex virus type 2. Milligan, G.N., Meador, M.G., Chu, C.F., Young, C.G., Martin, T.L., Bourne, N. J. Virol. (2005) [Pubmed]
  7. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. Campbell, M.E., Palfreyman, J.W., Preston, C.M. J. Mol. Biol. (1984) [Pubmed]
  8. Nucleotide sequence of the herpes simplex virus type 2 thymidine kinase gene. Swain, M.A., Galloway, D.A. J. Virol. (1983) [Pubmed]
  9. N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2) inhibitors. Hernandez, A.I., Familiar, O., Negri, A., Rodríguez-Barrios, F., Gago, F., Karlsson, A., Camarasa, M.J., Balzarini, J., Pérez-Pérez, M.J. J. Med. Chem. (2006) [Pubmed]
  10. Demonstration of viral thymidine kinase inhibitor and its effect on deoxynucleotide metabolism in cells infected with herpes simplex virus. Nutter, L.M., Grill, S.P., Dutschman, G.E., Sharma, R.A., Bobek, M., Cheng, Y.C. Antimicrob. Agents Chemother. (1987) [Pubmed]
  11. Phosphorylation of four acyclic guanosine analogs by herpes simplex virus type 2 thymidine kinase. Larsson, A., Tao, P.Z. Antimicrob. Agents Chemother. (1984) [Pubmed]
  12. Sites of integration of herpes simplex virus type-2 thymidine kinase gene in human chromosomes. Kit, S., Teitz, Y., Hazen, M., Qavi, H. Int. J. Cancer (1979) [Pubmed]
  13. Thymidine kinase mutations conferring acyclovir resistance in herpes simplex type 1 recombinant viruses. Sergerie, Y., Boivin, G. Antimicrob. Agents Chemother. (2006) [Pubmed]
  14. Characterization of an acyclovir-resistant herpes simplex virus type 2 strain isolated from a premature neonate. Oram, R.J., Marcellino, D., Strauss, D., Gustafson, E., Talarico, C.L., Root, A.K., Sharma, P.L., Thompson, K., Fingeroth, J.D., Crumpacker, C., Herold, B.C. J. Infect. Dis. (2000) [Pubmed]
  15. Analysis of herpes simplex virus-specific T cells in the murine female genital tract following genital infection with herpes simplex virus type 2. Milligan, G.N., Bernstein, D.I. Virology (1995) [Pubmed]
  16. Intranasal herpes simplex virus type 2 inoculation causes a profound thymidine kinase dependent cerebral inflammatory response in the mouse hindbrain. Boivin, G., Coulombe, Z., Rivest, S. Eur. J. Neurosci. (2002) [Pubmed]
  17. Differential roles of B cells and IFN-gamma-secreting CD4(+) T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice. Harandi, A.M., Svennerholm, B., Holmgren, J., Eriksson, K. J. Gen. Virol. (2001) [Pubmed]
  18. In situ polymerase chain reaction: localization of HSV-2 DNA sequences in infections of the nervous system. Gressens, P., Martin, J.R. J. Virol. Methods (1994) [Pubmed]
  19. Polyamine depletion and cell cycle manipulation in combination with HSV thymidine kinase/ganciclovir cancer gene therapy. Wahlfors, T., Karppinen, A., Jänne, J., Alhonen, L., Wahlfors, J. Int. J. Oncol. (2006) [Pubmed]
  20. Characterisation of penciclovir resistant acyclovir sensitive herpes simplex virus type 2 isolated from an AIDS patient. Pardeiro, M., Cuenca-Estrella, M., Fernández-Clúa, M.A., Santos-O'Connor, F., Tabarés, E., Gadea, I. J. Med. Virol. (2004) [Pubmed]
  21. Distinct thymidine kinases encoded by cowpox virus and herpes simplex virus contribute significantly to the differential antiviral activity of nucleoside analogs. Prichard, M.N., Williams, A.D., Keith, K.A., Harden, E.A., Kern, E.R. Antiviral Res. (2006) [Pubmed]
  22. HSV-1 and HSV-2 in herpes simplex encephalitis: a study of sixty-four cases in the United Kingdom. Dennett, C., Cleator, G.M., Klapper, P.E. J. Med. Virol. (1997) [Pubmed]
  23. Fusion of herpes simplex virus thymidine kinase to VP22 does not result in intercellular trafficking of the protein. Beerens, A.M., Rots, M.G., de Vries, E.F., Haisma, H.J. Int. J. Mol. Med. (2007) [Pubmed]
  24. Expression of immunity to intravaginal herpes simplex virus type 2 infection in the genital tract and associated lymph nodes. McDermott, M.R., Brais, P.L., PLoettsche, G.C., Evelegh, M.J., Goldsmith, C.H. Arch. Virol. (1987) [Pubmed]
  25. Intercellular trafficking and cytotoxicity of recombinant HSV-1 thymidine kinase fused with HSV-2 US11 RXP repeat peptide. Luo, C., Nawa, A., Yamauchi, Y., Kohno, S., Ushijima, Y., Goshima, F., Kikkawa, F., Nishiyama, Y. Virus Genes (2007) [Pubmed]
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