F ollowing ocular infection with herpes simplex virus type 1 (HSV-1), the virus travels in a retrograde direction toward neuronal cell bodies and establishes latency in trigeminal ganglia (TG) of infected mice (1-3). After establishment of latency in neurons, the latency-associated transcript (LAT) is the only viral product consistently detected in abundance in infected mouse, rabbit, and human TG (4-9). LAT is important for the high, wildtype (WT) rate of in vivo spontaneous (10) and induced (4) reactivation from latency. At various times throughout the life of the latently infected individual, the latent virus spontaneously reactivates and returns to the eye in an anterograde direction (1-3). The eye disease that is broadly referred to as herpes stromal keratitis (HSK) or corneal scarring (CS) occurs mainly as the result of virus reactivation rather than primary ocular infection in humans (11-15).Neurovirulence of HSV-1 strains can influence the eye disease in ocularly infected mice (16,17). Based on neurovirulence in animal studies, HSV-1 strains can be classified into two main categories: (i) avirulent HSV-1 strains, such as strains KOS and RE, which do not kill BALB/c mice or New Zealand White (NZW) rabbits following ocular infection and do not replicate efficiently in the eye without corneal scarification, and (ii) virulent HSV-1 strains, such as McKrae and its LAT (Ϫ) -derived virus, dLAT2903, that kill ϳ80% and ϳ50% of BALB/c mice and NZW rabbits, respectively, following ocular infection (18-21) and do not require corneal scarification for efficient ocular infection. Thus, in addition to the presence of LAT, the degree of HSV-1 virulence can also influence the level of recurrence.Following ocular infection, latent HSV genomes express LAT in a portion of those neurons maintaining them, and virus can be recovered by cocultivation of ex-planted ganglia (22-24). In contrast to spontaneous reactivation in rabbits and humans, spontaneous reactivation in the murine model of ocular HSV-1 is rare (25). Previously, it was suggested that the HSV-1 genome is maintained in a quiescent state in sensory neurons during latency in mice due to the absence of detectable viral protein synthesis. However, studies from mice indicate that lytic transcripts and proteins