Therapeutic efficacy of DNA encoding IFN-alpha1 against corneal HSV-1 infection.
OBJECTIVE
Type I interferons (IFN-alpha and -beta) are an innate immune component that plays a critical role in controlling herpes simplex virus type 1 (HSV-1) infection. We have previously shown that topical administration of a plasmid DNA encoding IFN-alpha1 onto mouse corneas prior to ocular HSV-1 infection provided prophylactic efficacy against HSV-1-induced encephalitis. As a result, the present study was undertaken to investigate the kinetics of the efficacy mediated by the IFN-alpha1 transgene following ocular challenge with HSV-1.


METHODS
Mice were ocularly infected with a lethal dose of HSV-1 (450 plaque forming units/eye, McKrae strain) following corneal scarification and topically administered the pCMV-IFN-alpha1 transgene or pCMV-beta (plasmid vector) starting at 12, 24, or 48 hr post infection. Cumulative survival of infected mice was recorded. In addition, the effect of the transgene on viral replication and viral gene expression was determined from tissues 3 and 6 days post infection by plaque assay and RT-PCR respectively.


RESULTS
Mice treated with the pCMV-IFNalpha1 transgene survived to a greater degree compared to mice topically administered the plasmid vector alone in a time-dependent manner. The protective effect correlated with a decrease in the viral load and expression of HSV-1 immediate early and early gene transcripts, infected cell protein-27 and thymidine kinase respectively in the trigeminal ganglion 6 days post infection.


CONCLUSIONS
These results suggest that the application of plasmid DNA encoding IFN-alpha1 transgene is beneficial as a therapeutic approach when applied early after HSV-1 infection of the corneas.
Noisakran
S J
SJ
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Carr
D J
DJ
D000818:Animals; D002522:Chlorocebus aethiops; D003315:Cornea / Q000294:innervation / Q000821:virology; D004247:DNA / Q000627:therapeutic use*; D017931:DNA Primers / Q000737:chemistry; D018792:Encephalitis, Viral / Q000517:prevention & control; D005260:Female; D005814:Genes, Viral / Q000187:drug effects; D015316:Genetic Therapy; D005822:Genetic Vectors; D006561:Herpes Simplex / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000502:physiology*; D016898:Interferon-alpha / Q000235:genetics*; D016849:Keratitis, Herpetic / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019076:Transgenes; D012668:Trigeminal Ganglion / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
D017931:DNA Primers; D016898:Interferon-alpha; D004247:DNA