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 syn ergistically inhibits replication of herpes simplex virus type 1. IFN- alpha treatment influenced the metabolism of exogenously supplied nucl eobases and nucleosides in a manner expected to contribute to synergis tic activity. IFN-alpha treatment of infected human cornea stromal cel ls or Vero cells significantly reduced steady-state levels of acid sol uble metabolites of thymine, as well as thymidine, that accumulate ear ly during virus replication but did not affect metabolism of thymine a nd thymidine in uninfected cells. IFN-alpha treatment significantly re duced the ability of uninfected cells to accumulate acid-soluble metab olites from guanine, but not guanosine. The effects of IFN-alpha. on n ucleobase/nucleoside metabolism could contribute to synergistic antivi ral activity by reducing the accumulation of thymidine/thymine metabol ites and decreasing the guanine taken into cells.