Ocular infection with HSV-1 continues to be a serious clinical problem despite the availability of effective
antivirals. Primary
infection with HSV-1 can involve ocular and adenaxial sites and can manifest as
blepharitis,
conjunctivitis, or corneal epithelial
keratitis. After initial
ocular infection, HSV-1 can establish
latent infection in the trigeminal ganglia for the lifetime of the host. During latency, the viral genome is retained in the neuron without producing
viral proteins. However, abundant transcription occurs at the region encoding the latency-associated transcript, which may play significant roles in the maintenance of latency as well as neuronal reactivation. Many host and viral factors are involved in HSV-1 reactivation from latency. HSV-1
DNA is shed into tears and saliva of most adults, but in most cases this does not result in lesions. Recurrent disease occurs as HSV-1 is carried by anterograde transport to the original site of
infection, or any other site innervated by the latently infected ganglia, and can reinfect the ocular tissues. Recurrent
corneal disease can lead to corneal
scarring, thinning, stromal opacity and neovascularization and, eventually,
blindness. In spite of intensive
antiviral and anti-inflammatory
therapy, a significant percentage of patients do not respond to
chemotherapy for herpetic necrotizing stromal
keratitis. Therefore, the development of
therapies that would reduce asymptomatic viral shedding and lower the risks of recurrent disease and transmission of the virus is key to decreasing the morbidity of ocular herpetic disease. This review will highlight basic HSV-1 virology, and will compare the animal models of latency, reactivation, and recurrent ocular disease to the current clinical data.