Resistance to ocular herpes simplex virus type 1 infection in IL-12 transgenic mice.
Interleukin-12 (IL-12) is a potent inflammatory cytokine that influences the innate and adaptive immune response to microbial pathogens including viruses. It was reasoned that constitutive IL-12 production in mice would enhance resistance to herpes simplex virus type 1 (HSV-1) infection. To test this hypothesis, transgenic mice expressing the p35 and p40 genes of IL-12 under a glial fibrillary acidic protein (GFAP) promoter were ocularly infected with HSV-1. These mice displayed increased survival and reduced viral titers in the eye, trigeminal ganglion (TG), and brain stem in comparison to wild type controls. Consistent with these results, HSV-1 immediate early and early gene expression were reduced to 50-130-fold in the trigeminal ganglion of infected transgenic mice compared to infected, non-transgenic counterparts as determined by real time PCR. Associated with viral resistance, IL-12 and IFN-gamma mRNA levels and IL-12 protein were elevated in the eyes of the transgenic versus non-transgenic mice during the acute infection. Collectively, the data show the inherent resistance of mice constitutively expressing IL-12 to ocular HSV-1 infection-an outcome that is independent of the adaptive immune system at the time of infection.
Al-Khatib
Khaldun
K
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Campbell
Iain L
IL
Carr
Daniel J J
DJ
D000818:Animals; D002522:Chlorocebus aethiops; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000502:physiology; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics / Q000502:physiology*; D016849:Keratitis, Herpetic / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D014709:Vero Cells; D014779:Virus Replication
D005904:Glial Fibrillary Acidic Protein; D018664:Interleukin-12; D007371:Interferon-gamma