NEUTROPHIL-MEDIATED SUPPRESSION OF VIRUS-REPLICATION AFTER HERPES-SIMPLEX VIRUS TYPE-1 INFECTION OF THE MURINE CORNEA

Herpes simplex virus type 1 (HSV-1) infection of the murine cornea ind uces the rapid infiltration of neutrophils. We investigated whether th ese cells could influence virus replication. BALB/c mice treated with monoclonal antibody (MAb) RB6-8C5 experienced a profound depletion of neutrophils in the bloodstream, spleen, and cornea. In these animals, virus titers in the eye were significantly higher than those in the im munoglobulin G-treated controls at 3 days postinfection. By day 9, vir us was no longer detectable in the controls, whereas titers of 10(3) t o 10(6) PFU were still present in the neutrophil-depleted hosts. Furth ermore, virus spread more readily to the skin and brains of MAb RB6-8C 5-treated animals, rendering them significantly more susceptible to HS V l-induced blepharitis and encephalitis. Only 25% of the treated anim als survived, whereas all of the controls lived. Although MAb RB6-8C5 treatment did not alter the CD4(+) T-cell, B-cell, natural killer cell , or macrophage populations, the CD8(+) T-cell population was partiall y reduced. Therefore, the experiments were repeated in severe combined immunodeficiency mice, which lack CD8(+) T cells. Again virus growth was found to be significantly elevated in the eyes, trigeminal ganglia , and brains of the MAb RB6-8C5-treated hosts. These results strongly indicate that in both immunocompetent and immunodeficient mice, neutro phils play a significant role in helping to control the replication an d spread of HSV-1 after corneal infection.