EFFECT OF INTERFERON-ALPHA ON THE STEADY-STATE LEVELS OF THYMINE, THYMIDINE, GUANINE, AND GUANOSINE METABOLITES IN HERPES-SIMPLEX VIRUS-TYPE 1-INFECTED CELLS
Wj. Obrien et al., EFFECT OF INTERFERON-ALPHA ON THE STEADY-STATE LEVELS OF THYMINE, THYMIDINE, GUANINE, AND GUANOSINE METABOLITES IN HERPES-SIMPLEX VIRUS-TYPE 1-INFECTED CELLS, Intervirology, 38(5), 1995, pp. 249-255
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.