INNATE AND ACQUIRED-IMMUNITY TO HERPES-SIMPLEX VIRUS TYPE-1

Immunization with heat-inactivated herpes simplex virus type 1 (HSV-I) 2-5 days before ocular infection reduced the frequency of establishme nt of latent HSV-1 infection in the trigeminal ganglion (TG); this ind uction of resistence coincided with reduced expression of IFN-gamma mR NA in the TG. Immunization with unrelated antigens was not protective. In part, this resistance to nervous system invasion correlated with t he appearance of serum antibody to HSV-1. Immunization reduced viral r eplication in the eye and trigeminal ganglion, and prevented HSV-1 spr ead to the cerebellum. IFN-gamma was detected in immunized mice 4 days postocular infection as determined by plaque reduction using neutrali zing Ab to IFN-alpha/beta and IFN-gamma. Injection of antibody (Ab) to IFN-alpha/beta and IFN-gamma administered al the time of immunization did not affect survival. Anti-IFN-gamma-treated mice had significantl y reduced levels of IFN in their serum. Treatment with anti-IFN-alpha/ beta Ab resulted in an elevation in viral replication as determined by the expression or latency associated transcripts in the TG of mice. L ikewise, there was a significant increase in the CD8, IL-12 (p40), and TNF-LU mRNA levels in the TG of the anti-IFN-alpha/beta-treated mice. TG explant cultures demonstrated that viral load was significantly in creased in the TG of anti-IFN-alpha/beta-treated mice relative to TG o f control mice 7 days after infection. The results suggest that exposu re to viral antigens 2-5 days before infection is an important determi nant of the extent of HSV-1 spread to the nervous system. Moreover, th e data suggest that both an antibody response and IFN-alpha/beta play a role in limiting the progress of infection from the peripheral tissu es to the central nervous system. (C) 1997 Academic Press.