title: Topical application of the cornea post-infection with plasmid DNA encoding interferon-alpha1 but not recombinant interferon-alphaA reduces herpes simplex virus type 1-induced mortality in mice.
abstract: A study was undertaken to compare the efficacy of recombinant interferon (rIFN)-alphaA to plasmid DNA encoding IFN-alpha1 against ocular herpes simplex virus type 1 (HSV-1) infection. The topical application of rIFN-alphaA (100-300 units/eye) onto the cornea of mice subsequently infected 24 h later with HSV-1 antagonized viral-induced mortality. The enhancement in cumulative survival in the rIFN-alphaA-treated mice correlated with a reduction of viral titers recovered in the eye and trigeminal ganglion (TG) at 3 and 6 days post-infection. The protective effect was site-specific such that when rIFN-alphaA was administered orally or intranasally, no efficacy against HSV-1 was observed. However, the protective effect was time-dependent. Specifically, when the rIFN-alphaA (100-1000 units/eye) was administered at 24 h post-infection, no protective effect was observed against HSV-1 compared to the vehicle-treated group. In contrast, plasmid DNA (100 microg/eye) containing the IFN-alpha1 transgene showed significant protection when topically applied 24 h post-infection. Although the transgene was found to traffic distal from the site of application (eye), including the trigeminal ganglion and the spleen where CD11b(+) and CD11c(+) cells express the transgene, the migration of the transgene did not correlate with efficacy. Collectively, the results suggest that naked DNA encoding type I IFN applied post-infection provides a greater degree of protection against ocular HSV-1 infection in comparison with recombinant protein effectively antagonizing viral replication and spread.
authors.affiliation: Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: S
authors.initials: S
authors.lastname: Noisakran
authors.forename: D J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002522:Chlorocebus aethiops; D003315:Cornea; D003316:Corneal Diseases / Q000401:mortality / Q000628:therapy / Q000821:virology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006561:Herpes Simplex / Q000401:mortality / Q000628:therapy*; D018259:Herpesvirus 1, Human; D007370:Interferon Type I / Q000235:genetics; D016898:Interferon-alpha / Q000235:genetics*; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000493:pharmacokinetics; D011994:Recombinant Proteins; D014709:Vero Cells; D019562:Viral Load; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000276:immunology
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins