Herpes simplex virus (HSV) infection is one of the leading causes of c
orneal blindness. This study compared the clinical, virologic, and imm
unopathologic features of primary and recurrent murine models of herpe
s simplex keratitis (HSK) in the National Institutes of Health (NIH) i
nbred mouse strain. Primary infection resulted in multiple epithelial
dendrites, followed by diffuse stromal opacification, symptoms that do
not mimic what is seen in human HSK. In contrast, recurrent infection
presented clinical features that included microdendrites, focal strom
al opacities, disciform endotheliitis, and corneal neovascularization,
which were similar to those observed in human disease. Immunohistoche
mical characterizations indicated that the number and duration of T ce
lls and macrophages in recurrent HSK resemble those observed in primar
y disease. Results also indicated that the amount of infectious virus
detected in the cornea during primary and recurrent disease was simila
r. However, when corneas were stained for HSV-I antigens, mice with pr
imary HSK displayed diffuse HSV antigen expression throughout the corn
ea, whereas HSV antigens were more focally distributed in recurrent di
sease. These data suggest that the clinical differences between the re
current and primary herpetic keratitis may, in part, reflect the diffe
rent distribution of HSV-1 antigens within the cornea.