title: Comparison of thymidine kinase activities indiced in cells productively infected with herpesvirus saimiri and herpes simplex virus.
abstract: The replication of unselected strains of herpesvirus saimiri (HVS) was sensitive to bromodeoxyuridine and bromovinyldeoxyuridine (BVdU) but insensitive to acycloguanosine (ACG), in contrast to the growth of herpes simplex virus (HSV) which was sensitive to all three analogues. Mutants of HVS resistant to bromodeoxyuridine and BVdU could be selected by growth in the presence of these inhibitors. Productive infections of owl monkey kidney or Vero cell cultures by unselected strains of HVS resulted in increases in a thymidine kinase (TK) activity which was deficient in cells infected with bromodeoxyuridine-resistant mutants of the virus. Induction of the virus enzyme promoted a net increase in the uptake and incorporation of exogenous labelled thymidine in the face of the progressive inhibition of the overall incorporation of [35S]methionine and [3H]uridine into productively infected cells. The TK induced in cells infected with HVS differed from the major activity of uninfected cells and resembled that encoded by HSV in its capacity to phosphorylate iododeoxyuridine and in the sensitivity of all the thymidine phosphorylating activity to competition by BVdU. However, in contrast to the HSV TK, which phosphorylated deoxycytidine and iododeoxycytidine relatively efficiently and was sensitive to ACG, the HVS enzyme did not phosphorylate deoxycytidine or iododeoxycytidine and was insensitive to ACG. Whilst HVS, therefore, shares the characteristic of other members of the herpesvirus group of inducing a novel TK, the properties of the HVS-induced enzyme differ significantly from the enzyme of the prototype herpesvirus, HSV. The properties of the HVS TK are nonetheless sufficiently distinct from those of the uninfected cell to provide a possible basis for selective antiviral chemotherapy based on preferential phosphorylation of nucleoside analogues such as BVdU by infected cells.
mesh_terms: D000212:Acyclovir; D000818:Animals; D001029:Aotus trivirgatus; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004790:Enzyme Induction; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006567:Herpesvirus 2, Saimiriine / Q000201:enzymology / Q000254:growth & development*; D007065:Idoxuridine / Q000378:metabolism; D009154:Mutation; D018139:Simplexvirus / Q000201:enzymology / Q000254:growth & development*; D013936:Thymidine / Q000378:metabolism; D013937:Thymidine Kinase / Q000378:metabolism*
chemical_list: C020235:brivudine; D006147:Guanine; D013937:Thymidine Kinase; D001973:Bromodeoxyuridine; D007065:Idoxuridine; D013936:Thymidine; D000212:Acyclovir