Antiviral Activity of an Oligo(nucleoside Methylphosphonate) That Targets HSV-1 Immediate-Early Pre-mRNA 4,5 Is Augmented by Cotreatment with Replication-Defective Adenovirus

Replication-defective adenovirus p259A caused a 400-fold increase in the sequence-specific antiherpetic activity of oligo(nucleoside methylphosphonate) (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 BODIPY-conjugated IE4,5SA revealed intracellular localization within endocytic-like vesicles with minimal cytoplasmic and intranuclear distribution. Diffuse staining over the entire cell was observed in cell cotreated with the BODIPY-conjugated IE4,5SA and p259A virus. This effect was not observed in cells cotreated with the BODIPY-conjugated ONMP and heated p259A virus. We interpret these findings to indicate that p259A augments IE4,5SA antiherpetic activity presumably via its ability to increase ONMP uptake and release from endocytic-like vesicles.