Innate and acquired immunity to Herpes simplex virus type 1

Abstract

Immunization with heat-inactivated herpes simplex virus type 1 (HSV-1) 2-5 days before ocular infection reduced the frequency of establishment of latent HSV-1 infection in the trigeminal ganglion (TG); this induction of resistence coincided with reduced expression of IFN-γ mRNA in the TG. Immunization with unrelated antigens was not protective. In part, this resistance to nervous system invasion correlated with the appearance of serum antibody to HSV-1. Immunization reduced viral replication in the eye and trigeminal ganglion, and prevented HSV-1 spread to the cerebellum. IFN-γ was detected in immunized mice 4 days postocular infection as determined by plaque reduction using neutralizing Ab to IFN-α/β and IFN-γ. Injection of antibody (Ab) to IFN-α/β and IFN-γ administered at the time of immunization did not affect survival. Anti-IFN-γ-treated mice had significantly reduced levels of IFN in their serum. Treatment with anti-IFN-α/β Ab resulted in an elevation in viral replication as determined by the expression of latency associated transcripts in the TG of mice. Likewise, there was a significant increase in the CD8, IL-12 (p40), and TNF-α mRNA levels in the TG of the anti-IFN-α/β-treated mice. TG explant cultures demonstrated that viral load was significantly increased in the TG of anti-IFN-α/β-treated mice relative to TG of control mice 7 days after infection. The results suggest that exposure to viral antigens 2-5 days before infection is an important determinant of the extent of HSV-1 spread to the nervous system. Moreover, the data suggest that both an antibody response and IFN-α/β play a role in limiting the progress of infection from the peripheral tissues to the central nervous system.