Herpes simplex virus type 1 strain KOS-63 does not cause acute or recurrent ocular disease and does not reactivate ganglionic latency in vivo.

The virological, clinical, and histopathological manifestations of acute and experimentally reactivated infections of eyes and trigeminal ganglia have been studied following intranasal infection of rabbits with herpes simplex virus type 1 (strain KOS-63). All animals shed virus in nasal secretions, but only three shed virus in tear film during the first 12 days of infection. No animal developed clinical or histological evidence of corneal or retinal ocular disease at any time after infection. KOS-63 established trigeminal ganglionic latency; viral RNA, restricted to neuronal nuclei, was detected by in situ hybridization, and virus was recovered from co-cultivation cultures of nervous tissue, but not from cell-free homogenates. Reactivation of latent trigeminal ganglionic infection was attempted by intravenous administration of cyclophosphamide, followed by dexamethasone 24 h later. Injection of the drugs failed to reactivate KOS-63 latency; no animal shed virus in nasal or ocular secretions, and no animal developed gross or microscopic corneal lesions. In addition, viral antigens were not detected by immunofluorescence microscopy in ganglia from rabbits subjected to the drug protocol, and virus was only recovered from ganglia by in vitro co-cultivation reactivation techniques. The failure of KOS-63 to reactivate was not due to an inherent failure of populate and infect the ganglion, because the virus did not reactivate from ganglia that contained many latently infected cells. These studies demonstrate that, although KOS-63 is neuroinvasive and capable of establishing latency, it is virtually nonvirulent for the eye, and cannot be reactivated by a systemic immunosuppressive trigger known to reactivate other HSV-1 strains.