Corneal nerve disruption reactivates virus in rabbits latently infected with HSV-1

Abstract

Trauma, inflammation, and neuronal stimulation or damage can reactive latent herpes simplex virus type 1 (HSV-1). The innervation density of the corneal epithelium is 300-600 times that of skin and, therefore, corneal nerve disruption could provide a strong stimulus for HSV-1 reactivation. This study has documented HSV-1 ocular reactivation following three methods of corneal nerve disruption in rabbits. Twenty HSV-1 latently infected rabbits (26 eyes) were divided into three groups: 7 rabbits received uniocular cryogenic injury, 7 rabbits underwent uniocular anterior superficial keratectomy, and 6 rabbits had binocular transection of the corneal nerves at the corneoscleral limbus which, in contrast to the other treatments, produced minimal epithelial change. Opposite eyes in the first two groups of rabbits were left undisturbed to serve as HSV-1 infected controls. Three additional rabbits, not infected with HSV-1, underwent gold chloride impregnation of the corneal nerves for light microscopic documentation of corneal nerve damage induced by each procedure. On all HSV-1 infected eyes, daily HSV-1 ocular cultures were obtained for 7 consecutive days. All three procedures resulted in marked corneal nerve destruction and degeneration. HSV-1 shedding occurred in 5/7 (71%) of the eyes that underwent cryogenic lesioning; in 5/7 (71%) of the eyes that underwent anterior keratectomy; and in 8/12 (67%) of the eyes that had the corneal nerves transected at the corneoscleral limbus. Only 4 (29%) of the 14 control eyes had positive HSV-1 ocular cultures. This investigation provides strong evidence that corneal nerve disruption is correlated with ocular HSV-1 reactivation.