Increased pathology in herpes stromal keratitis results from differences in local, and not systemic, immune responses (VIR5P.1028)

Abstract

Abstract Harboring latent herpes simplex virus type 1 (HSV-1) in the trigeminal ganglion (TG) and periodic shedding of virus at the corneal surface can be asymptomatic or can trigger an immunopathological response called herpes stromal keratitis that leads to progressive scarring and visual impairment. Our goal is to understand the events that differentiate an asymptomatic from a pathological HSV-1 infection. To this end we infected mice with two different strains of HSV-1: RE that causes progressive corneal opacity, and KOS that induces no overt corneal pathology. The kinetics of viral clearance and the latent viral load in the TG at 30 days post-infection (dpi) were similar following corneal infection with the two HSV-1 strains. However, the pathogenic RE strain induced a stronger CD4 and CD8 T cell response in the draining lymph nodes and TG at 8 dpi that persisted in the TG through 30 dpi. Interestingly, bilateral infections with RE in one eye and KOS in the other resulted in pathology only in the RE infected eye, suggesting that the increased immunopathology caused by the RE strain reflects local differences in the cornea or ipsilateral TG, and not differences in the systemic immune response. We are currently testing the hypothesis that greater viral gene expression by the RE strain during latency results in a larger T cell infiltrate in both the cornea and the TG.