Fig. 3. Factors that contribute to Herpes Stromal Keratitis (HSK).

After a predominantly sub-clinical primary infection, HSV-1 gains access to sensory neurons and enters a latent state within trigeminal ganglion neurons indefinitely. Spontaneously or during times of immune suppression, HSV-1 can reactivate and virions can be deposited at the cornea resulting in an inflammatory response. Repeated reactivation events result in: (1) increased recruitment of inflammatory immune cells, (2) the production of inflammatory cytokines/chemokines, (3) disruption of sensory nerves, and (4) the initiation of complement, which preferentially targets sensory nerves. Because HSK is a multi-factoral disease, these processes all contribute to disease and ultimately result in tissue damage, fibrosis, and eventual blindness.