ANTIVIRAL ACTIVITY OF AN OLIGO(NUCLEOSIDE METHYLPHOSPHONATE) THAT TARGETS HSV-1 IMMEDIATE-EARLY PRE-MESSENGER-RNA-4,5 IS AUGMENTED BY COTREATMENT WITH REPLICATION-DEFECTIVE ADENOVIRUS

Replication-defective adenovirus p259A caused a 400-fold increase in t he sequence-specific antiherpetic activity of oligo(nucleoside methylp hosphonate) (ONMP) IE4,5SA. Herpes simplex virus type 1 (HSV-1) growth was not inhibited in cells exposed to p259A in the absence of IE4,5SA or in cells cotreated with IE4,5SA and heated (10 minutes, 90 degrees C) p259A virus, Fluorescent microscopy of Vero cells treated with BOD IPY-conjugated IE4,5SA revealed intracellular localization within endo cytic-like vesicles with minimal cytoplasmic and intranuclear distribu tion. Diffuse staining over the entire cell was observed in cell cotre ated with the BODIPY-conjugated IE4,5SA and p259A virus, This effect w as not observed in cells cotreated with the BODIPY-conjugated ONMP and heated p259A virus. We interpret these findings to indicate that p259 A augments IE4,5SA antiherpetic activity presumably via its ability to increase ONMP uptake and release from endocytic-like vesicles.