Herpes simplex virus stromal keratitis is not titer-dependent and does not correlate with neurovirulence

We developed a murine model of ocular herpes simplex virus (HSV) disease which is particularly suited for testing stromal keratitis because most animals show some evidence of infection. Using this model, we characterized the ocular disease patterns caused by ten recent low-passage clinical isolates of HSV-1, as well as those caused by the established laboratory strains HSV-1 KOS and HSV-2 333. Viral strains were evaluated for their ability to cause stromal keratitis, blepharitis, vascularization of the cornea, and mortality. The model was not useful for scoring epithelial keratitis. The ocular disease caused by the recent isolates ranged from very mild disease to severe stromal keratitis. Some of the recent isolates caused disease as severe as the two laboratory strains. A comparison of the virulence characteristics expressed by various HSV strains indicated that the ability to cause stromal disease was correlated with vascularization of the cornea (correlation coefficient = 0.797, P less than 0.001) and was not correlated with the neurovirulence of the strains (correlation coefficient 0.045, P greater than 0.05). The severity of stromal keratitis was not dependent on the amount of inoculum over the range tested and a strain causing severe stromal keratitis caused severe ocular disease even when mixed with a nonstromal strain at ratios of 10:1, 100:1, and 1000:1.