Phosphorylation of 5-bromodeoxycytidine in Cells Infected with Herpes Simplex Virus

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1973 Dec 1

PMID 4359489

Citations 19

Authors

G M Cooper

Affiliations

Soon will be listed here.

Abstract

5-Bromodeoxycytidine is phosphorylated to 5-bromodeoxycytidine 5'-monophosphate in extracts of cells infected with herpes simplex virus but not in extracts of uninfected cells. The conversion of 5-bromodeoxycytidine to nucleotides and its utilization for DNA synthesis in uninfected cells occurs by deamination of 5-bromodeoxycytidine to 5-bromodeoxyuridine followed by phosphorylation of 5-bromodeoxyuridine to 5-bromodeoxyuridine 5'-monophosphate. In contrast, in cells infected with herpes simplex virus, 5-bromodeoxycytidine is phosphorylated directly to 5-bromodeoxycytidine 5'-monophosphate, which can then be deaminated to 5-bromodeoxyuridine 5'-monophosphate and incorporated into DNA. These results indicate a difference in the substrate specificity of nucleoside kinases induced by herpes simplex virus and the enzymes present in uninfected cells. It is suggested that this difference in substrate specificity between virus-induced and host-cell enzymes may allow selective chemotherapy of herpes simplex infections with 5-bromo- or 5-iododeoxycytidine.

Citing Articles

Effect of adenosine deaminase upon the antiviral activity in vitro of adenine arabinoside for vaccinia virus.

Connor J, Sweetman L, Carey S, Stuckey M, Buchanan R Antimicrob Agents Chemother. 1974; 6(5):630-6.

PMID: 15825318 PMC: 444705. DOI: 10.1128/AAC.6.5.630.

Reactivation of thymidine kinase-defective herpes simplex virus is enhanced by nucleoside.

Tenser R, Gaydos A, Hay K J Virol. 1996; 70(2):1271-6.

PMID: 8551594 PMC: 189942. DOI: 10.1128/JVI.70.2.1271-1276.1996.

Incorporation of 5-substituted analogs of deoxycytidine into DNA of herpes simplex virus-infected or - transformed cells without deamination to the thymidine analog.

Fox L, Dobersen M, Greer S Antimicrob Agents Chemother. 1983; 23(3):465-76.

PMID: 6303214 PMC: 184670. DOI: 10.1128/AAC.23.3.465.

Capacity of deoxycytidine to selectively antagonize cytotoxicity of 5-halogenated analogs of deoxycytidine without loss of antiherpetic activity.

Fox L, Mekras J, Bagwell C, GREER S Antimicrob Agents Chemother. 1982; 22(3):431-41.

PMID: 6291452 PMC: 183762. DOI: 10.1128/AAC.22.3.431.

Construction of poxviruses as cloning vectors: insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus.

Panicali D, Paoletti E Proc Natl Acad Sci U S A. 1982; 79(16):4927-31.

PMID: 6289324 PMC: 346798. DOI: 10.1073/pnas.79.16.4927.

References

BRESNICK E, Thompson U . Properties of deoxythymidine kinase partially purified from animal tumors. J Biol Chem. 1965; 240(10):3967-74. View

Kaufmann H . In vivo studies with antiviral agents. Ann N Y Acad Sci. 1965; 130(1):168-80. DOI: 10.1111/j.1749-6632.1965.tb12550.x. View

LEOPOLD I . Clinical experience with nucleosides in herpes simplex eye infections in man and animals. Ann N Y Acad Sci. 1965; 130(1):181-91. DOI: 10.1111/j.1749-6632.1965.tb12551.x. View

RENIS H, Buthala D . Development of resistance to antiviral drugs. Ann N Y Acad Sci. 1965; 130(1):343-54. DOI: 10.1111/j.1749-6632.1965.tb12568.x. View

CAMIENER G, Smith C . Studies of the enzymatic deamination of cytosine arabinoside. I. Enzyme distribution and species specificity. Biochem Pharmacol. 1965; 14(10):1405-16. DOI: 10.1016/0006-2952(65)90175-9. View

NAIB Z, Nahmias A, Josey W . Cytology and histopathology of cervical herpes simplex infection. Cancer. 1966; 19(7):1026-31. DOI: 10.1002/1097-0142(196607)19:7<1026::aid-cncr2820190718>3.0.co;2-#. View

KLEMPERER H, Haynes G, Shedden W, Watson D . A virus-specific thymidine kinase in BHK-21 cells infected with herpes simplex virus. Virology. 1967; 31(1):120-8. DOI: 10.1016/0042-6822(67)90015-3. View

Momparler R, Fischer G . Mammalian deoxynucleoside kinase. I. Deoxycytidine kinase: purification, properties, and kinetic studies with cytosine arabinoside. J Biol Chem. 1968; 243(16):4298-304. View

CAMIENER G . Studies of the enzymatic deamination of ara-cytidine. V. inhibition in vitro and in vivo by tetrahydrouridine and other reduced pyrimidine nucleosides. Biochem Pharmacol. 1968; 17(9):1981-91. DOI: 10.1016/0006-2952(68)90114-7. View

10.

Perera P, Morrison J . Evidence for the induction of a new deoxycytidine kinase in cells infected with herpes virus. Biochem J. 1970; 117(2):21P-22P. PMC: 1178897. DOI: 10.1042/bj1170021pb. View

11.

Epstein M . Aspects of the EB virus. Adv Cancer Res. 1970; 13:383-411. DOI: 10.1016/s0065-230x(08)60169-4. View

12.

Neil G, Moxley T, Manak R . Enhancement by tetrahydrouridine of 1-beta-D-arabinofuranosylcytosine (cytarabine) oral activity in L1210 leukemic mice. Cancer Res. 1970; 30(8):2166-72. View

13.

Kit S, DUBBS D, ANKEN M . Altered properties of thymidine kinase after infection of mouse fibroblast cells with herpes simplex virus. J Virol. 1967; 1(1):238-40. PMC: 375522. DOI: 10.1128/JVI.1.1.238-240.1967. View

14.

RENIS H . Comparison of cytotoxicity and antiviral activity of 1-beta-D-arabino-furanosyl-5-iodocytosine with related compounds. Cancer Res. 1970; 30(1):189-94. View

15.

Duff R, Rapp F . Properties of hamster embryo fibroblasts transformed in vitro after exposure to ultraviolet-irradiated herpes simplex virus type 2. J Virol. 1971; 8(4):469-77. PMC: 376220. DOI: 10.1128/JVI.8.4.469-477.1971. View

16.

Cohen G . Ribonucleotide reductase activity of synchronized KB cells infected with herpes simplex virus. J Virol. 1972; 9(3):408-18. PMC: 356313. DOI: 10.1128/JVI.9.3.408-418.1972. View

17.

Wellings P, Awdry P, Bors F, Jones B, Brown D, Kaufman H . Clinical evaluation of trifluorothymidine in the treatment of herpes simplex corneal ulcers. Am J Ophthalmol. 1972; 73(6):932-42. DOI: 10.1016/0002-9394(72)90463-1. View

18.

Cooper G, Greer S . The effect of inhibition of cytidine deaminase by tetrahydrouridine on the utilization of deoxycytidine and 5-bromodeoxycytidine for deoxyribonucleic acid synthesis. Mol Pharmacol. 1973; 9(6):698-703. View

19.

Cooper G, Greer S . Phosphorylation of 5-halogenated deoxycytidine analogues by deoxycytidine kinase. Mol Pharmacol. 1973; 9(6):704-10. View

20.

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View