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-inf ection assay and in an ocular HSV-1 infection model of mice. In the in vitr o assay, transfection of mouse fibroblasts with the IFN-beta transgene resu lted in a 17-fold or greater reduction in the viral load of HSV-1 at a mult iplicity of infection (MOI) of 1 compared to that of those mice treated wit h the plasmid control. RT-PCR analysis of representative immediate early (I CP27), early (thymidine kinase, TK) and late (VP16) viral genes found no ch anges in the level of expression comparing the IFN-beta transgene- to the v ector-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 I FN-beta onto mouse cornea enhanced cumulative survival and significantly re duced 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 plasmi d vector control or normal saline. Neutralizing antibody to IFN-beta blocke d the protective effect elicited by the IFN-beta transgene. Unlike the in v itro experiment, viral gene expression was reduced in the trigeminal gangli on of mice pre-treated 24 h with the IFN-beta transgene day 3 (ICP27 and VP 16) and day 6 (ICP27, TK, DNA polymerase, and VP16) post-infection in compa rison to mice treated with the plasmid vector control as determined by semi -quantitative RT-PCR. (C) 2000 Published by Elsevier Science B.V.