Deoxyribonucleoside triphosphate pools of herpes simplex virus infected cells: the influence of selective antiherpes agents and the role of the deaminase pathway.
The effect of 5-methoxymethyl-2'-deoxycytidine (MMdCyd), in combination with tetrahydrodeoxyuridine (H4dUrd) and 5-methoxymethyl-2'-deoxyuridine (MMdUrd) on deoxyribonucleoside triphosphate pools was assessed. The dNTP pool content was almost 5 times as high in herpes simplex virus (HSV) infected VERO cells compared with mock-infected cells. Significant differences in dNTP pool sizes were observed with the different treatments. Treatment of HSV-infected cells with MMdCyd and MMdUrd resulted in a massive expansion of the dTTP pool, whereas pools of dCTP and dGTP were not affected substantially. MMdUrd and MMdCyd produced dATP pools that were 4 and 2.5 times that of the controls, respectively. Treatment with H4dUrd resulted in the dCTP pool increasing 12 times and barely detectable levels of dTTP. MMdCyd in combination with H4dUrd resulted in a marked reduction of the total deoxyribonucleoside triphosphate level. These results indicate that during viral replication the bulk of the thymidine nucleotides are derived from the dCyd/dCMP deaminase de novo pathway.
Aduma
P J
PJ
Department of Physiological Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Gupta
S V
SV
Stuart
A L
AL
Tourigny
G
G
D000818:Animals; D001665:Binding Sites; D003564:Cytidine Deaminase; D003641:Deamination; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism*; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D009700:Nucleoside Deaminases / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects / Q000502:physiology*; D013767:Tetrahydrouridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013942:Thymine Nucleotides / Q000378:metabolism; D014709:Vero Cells
D003845:Deoxycytosine Nucleotides; D003854:Deoxyribonucleotides; D013942:Thymine Nucleotides; D003841:Deoxycytidine; C071169:5-methoxymethyl-2-deoxycytidine; D013767:Tetrahydrouridine; C024107:2'-deoxycytidine 5'-triphosphate; C052729:2'-deoxytetrahydrouridine; C024722:5-methoxymethyl-2'-deoxyuridine; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase; C024157:thymidine 5'-triphosphate; D003857:Deoxyuridine