IMMUNIZATION WITH HSV-1 ANTIGEN RAPIDLY PROTECTS AGAINST HSV-1-INDUCED ENCEPHALITIS AND IS IFN-GAMMA INDEPENDENT

Herpes simplex virus type 1 (HSV-1) infection of mice frequently culmi nates in fatal encephalitis. Intraperitoneal administration of heat-in activated HSV-1 0-5 days before infection (active immunization) protec ted mice from encephalitis. In addition, active immunization 2-5 days before ocular infection with HSV-1 reduced the frequency of establishm ent of latent HSV-I infection in the trigeminal ganglion (TG), However , intraperitoneal administration of heat-inactivated HSV-1 did not ind uce interferon (IFN) production in the peritoneum or serum, as determi ned by bioassay and ELISA, Intraperitoneal administration of heat-atte nuated HSV-1 elicited IFN-gamma but not type I IFN production in the p eritoneum, The production of IFN-gamma correlated with the infiltratio n of CD4 and CD8 cells in the peritoneum as determined by RT-PCR, In a ddition, there was a significant increase in interleukin (IL)-12 p40, IL-12p35, IL-6, IL-10, and IFN-gamma mRNA in peritoneal cells, as dete rmined by RT-PCR following immunization with heat-attenuated HSV-1, wh ich was not observed using heat-inactivated HSV-1, The results suggest that resistance to HSV-I is induced rapidly following immunization wi th viral antigen but that protection against encephalitis is independe nt of the cytokines that are generated in the peritoneum.