The application of a plasmid DNA encoding IFN-alpha 1 postinfection enhances cumulative survival of herpes simplex virus type 2 vaginally infected mice.
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.
Härle
P
P
Departments of Ophthalmology, Microbiology, and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Noisakran
S
S
Carr
D J
DJ
D000208:Acute Disease; D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000276:immunology; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004279:DNA, Viral / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D017930:Genes, Reporter / Q000276:immunology; D006558:Herpes Genitalis / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D007111:Immunity, Cellular / Q000235:genetics; D007115:Immunization Schedule; D016898:Interferon-alpha / Q000008:administration & dosage / Q000235:genetics*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007739:L Cells; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D015996:Survival Rate; D014162:Transfection; D019076:Transgenes / Q000276:immunology; D014621:Vagina / Q000276:immunology / Q000821:virology; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D000998:Antiviral Agents; D004279:DNA, Viral; D022301:Herpes Simplex Virus Vaccines; D016898:Interferon-alpha; D007371:Interferon-gamma