Effect of interferon-alpha on the steady-state levels of thymine, thymidine, guanine, and guanosine metabolites in herpes simplex virus-type 1-infected cells.
Interferon-alpha (IFN-alpha) combined with acyclic guanine analogs synergistically inhibits replication of herpes simplex virus type 1. IFN-alpha treatment influenced the metabolism of exogenously supplied nucleobases and nucleosides in a manner expected to contribute to synergistic activity. IFN-alpha treatment of infected human cornea stromal cells or Vero cells significantly reduced steady-state levels of acid soluble metabolites of thymine, as well as thymidine, that accumulate early during virus replication but did not affect metabolism of thymine and thymidine in uninfected cells. IFN-alpha treatment significantly reduced the ability of uninfected cells to accumulate acid-soluble metabolites from guanine, but not guanosine. The effects of IFN-alpha on nucleobase/nucleoside metabolism could contribute to synergistic antiviral activity by reducing the accumulation of thymidine/thymine metabolites and decreasing the guanine taken into cells.
O'Brien
W J
WJ
Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, USA.
Piotrowski
K
K
Taylor
J L
JL
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism; D006147:Guanine / Q000378:metabolism*; D018259:Herpesvirus 1, Human; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D012265:Ribonucleotides / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism*; D013941:Thymine / Q000378:metabolism*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D003854:Deoxyribonucleotides; D016898:Interferon-alpha; D012265:Ribonucleotides; D006147:Guanine; D012313:RNA; D004247:DNA; D013941:Thymine; D013936:Thymidine; D000212:Acyclovir