Innate and acquired immunity to herpes simplex virus type 1.
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 resistance coincided with reduced expression of IFN-gamma 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-gamma was detected in immunized mice 4 days postocular infection as determined by plaque reduction using neutralizing Ab to IFN-alpha/beta and IFN-gamma. Injection of antibody (Ab) to IFN-alpha/beta and IFN-gamma administered at the time of immunization did not affect survival. Anti-IFN-gamma-treated mice had significantly 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 of latency associated transcripts in the TG of mice. Likewise, there was a significant increase in the CD8, IL-12 (p40), and TNF-alpha mRNA levels in the TG of the anti-IFN-alpha/beta-treated mice TG explant cultures demonstrated that viral load was significantly increased in the TG of anti-IFN-alpha/beta-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-alpha/beta play a role in limiting the progress of infection from the peripheral tissues to the central nervous system.
Halford
W P
WP
Department of Microbiology and Immunology, Louisiana State University Medical Center, New Orleans 70112-1393, USA.
Veress
L A
LA
Gebhardt
B M
BM
Carr
D J
DJ
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage; D001483:Base Sequence; D002353:Carrier State / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002494:Central Nervous System Infections / Q000209:etiology / Q000276:immunology / Q000821:virology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006561:Herpes Simplex / Q000209:etiology / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D007372:Interferons / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000276:immunology / Q000821:virology; D014611:Vaccination; D014709:Vero Cells
D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D017931:DNA Primers; D007372:Interferons