RNA-dependent protein kinase is required for alpha-1 interferon transgene-induced resistance to genital herpes simplex virus type 2.
We investigated the mechanism of resistance to genital herpes simplex virus type 2 (HSV-2) infection in mice transfected with the murine alpha-1 interferon (IFN-alpha1) transgene. In situ transfection of mice with the IFN-alpha1 transgene resulted in an elevation in an IFN-responsive gene, RNA-dependent protein kinase (PKR), but not 2',5'-oligoadenylate synthetases (OAS), in vaginal tissue. Coupled with the finding that mice lacking a functional PKR pathway were no longer resistant to genital HSV-2 infection following transfection with the IFN-alpha1 transgene in comparison to wild-type mice or mice lacking a functional OAS pathway, these results suggest that PKR is the dominant antiviral pathway activated by the IFN-alpha1 transgene.
Carr
Daniel J J
DJ
Department of Ophthalmology, DMEI #415, The University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA. dan-carr@ouhsc.edu
Tomanek
Lisa
L
Silverman
Robert H
RH
Campbell
Iain L
IL
Williams
Bryan R G
BR
D000818:Animals; D006558:Herpes Genitalis / Q000276:immunology*; D016898:Interferon-alpha / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D014162:Transfection; D019076:Transgenes; D019892:eIF-2 Kinase / Q000502:physiology*
D016898:Interferon-alpha; D019892:eIF-2 Kinase