The application of a plasmid DNA encoding IFN-alpha 1 postinfection enhances cumulative survival of herpes simplex virus type 2 vaginally infected mice

Using a hormonally induced susceptibility mouse model to investigate vagina l HSV type 2 (HSV-2) infection, a study was undertaken to determine the eff icacy of a plasmid DNA encoding IFN-alpha1 introduced into the vaginal lume n postinfection (PI), Mice infected with HSV-2 intravaginally and treated i ntravaginally 24 h later with 100 mug DNA encoding IFN-alpha1 showed enhanc ed survival (10/15) in comparison to mice treated with 100 mug plasmid DNA vector alone (3/10) or vehicle (4/27), In contrast, mice receiving recombin ant IFN-alphaA (5-500 U/vagina) 24 h PI showed no significant survival in c omparison to the vehicle (saline)treated group. The protective effect was t ime dependent in that mice receiving the IFN-alpha1 transgene 48 h PI succu mbed at a rate similar to the plasmid DNA vector-treated group. The increas e in cumulative survival elicited by the transgene corresponded with a redu ction in viral replication and Ag expressed in the vaginal epithelium early (i.e., 3 days PI) during acute infection and replicating virus recovered i n the spinal cord day 7 PI. By day 7 PI, HSV-2 glycoprotein B transcript ex pression was no longer detectable in vaginal tissue from the IFN-alpha1 tra nsgene-treated group (0/8) compared with levels expressed in plasmid vector -treated controls (4/6 mice surveyed were positive). Collectively, these re sults suggest the application of DNA encoding type I IFN is an effective an d alternative approach to currently prescribed therapies in controlling vag inal HSV-2 infection by antagonizing viral replication.