A plasmid construct encoding murine interferon beta antagonizes the replication of herpes simplex virus type I in vitro and in vivo.

In the present study, we employed a plasmid DNA encoding murine interferon (IFN)-beta to assess its antiviral efficacy in an in vitro transfection-infection assay and in an ocular HSV-1 infection model of mice. In the in vitro assay, transfection of mouse fibroblasts with the IFN-beta transgene resulted in a 17-fold or greater reduction in the viral load of HSV-1 at a multiplicity of infection (MOI) of 1 compared to that of those mice treated with the plasmid control. RT-PCR analysis of representative immediate early (ICP27), early (thymidine kinase, TK) and late (VP16) viral genes found no changes in the level of expression comparing the IFN-beta transgene- to the vector-treated control group, suggesting that the IFN-beta transgene may act at the post-transcriptional level of viral replication. In the ocular HSV-1 infection model, topical application of the plasmid DNA encoding murine IFN-beta onto mouse cornea enhanced cumulative survival and significantly reduced the viral load of HSV-1 in the eyes and trigeminal ganglia of mice at both day 3 and 6 post-infection compared with mice treated with the plasmid vector control or normal saline. Neutralizing antibody to IFN-beta blocked the protective effect elicited by the IFN-beta transgene. Unlike the in vitro experiment, viral gene expression was reduced in the trigeminal ganglion of mice pre-treated 24 h with the IFN-beta transgene day 3 (ICP27 and VP16) and day 6 (ICP27, TK, DNA polymerase, and VP16) post-infection in comparison to mice treated with the plasmid vector control as determined by semi-quantitative RT-PCR.