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

Abstract

Using a hormonally induced susceptibility mouse model to investigate vaginal HSV type 2 (HSV-2) infection, a study was undertaken to determine the efficacy of a plasmid DNA encoding IFN-alpha1 introduced into the vaginal lumen postinfection (PI). Mice infected with HSV-2 intravaginally and treated intravaginally 24 h later with 100 microg DNA encoding IFN-alpha1 showed enhanced survival (10/15) in comparison to mice treated with 100 microg plasmid DNA vector alone (3/10) or vehicle (4/27). In contrast, mice receiving recombinant IFN-alphaA (5-500 U/vagina) 24 h PI showed no significant survival in comparison to the vehicle (saline)-treated group. The protective effect was time dependent in that mice receiving the IFN-alpha1 transgene 48 h PI succumbed at a rate similar to the plasmid DNA vector-treated group. The increase in cumulative survival elicited by the transgene corresponded with a reduction in viral replication and Ag expressed in the vaginal epithelium early (i.e., 3 days PI) during acute infection and replicating virus recovered in the spinal cord day 7 PI. By day 7 PI, HSV-2 glycoprotein B transcript expression was no longer detectable in vaginal tissue from the IFN-alpha1 transgene-treated group (0/8) compared with levels expressed in plasmid vector-treated controls (4/6 mice surveyed were positive). Collectively, these results suggest the application of DNA encoding type I IFN is an effective and alternative approach to currently prescribed therapies in controlling vaginal HSV-2 infection by antagonizing viral replication.