Abstract
Purpose:
Corneal herpes simplex virus (HSV) infection and inflammation leads to corneal scarring, ulcers, and neovascularization. Despite advances in antiviral therapies that have reduced HSV morbidity, the development of an effective vaccine remains of considerable interest. Pathogenic spread of virus relies on axonal transport of viral DNA. We recently demonstrated that HSV viral protein Us9 and particularly the sequence of nine amino acids from 30 to 38 play a critical role in genome anterograde axonal transport. A mouse ocular model was used to test the hypothesis that ocular pre-infection with a mutant HSV Us9-30 viral strain may reduce the immune and clinical response of a subsequent wild-type HSV challenge infection.
Methods:
Corneal epithelium was removed from the right eye of FVB wild-type mice and infected with either sterile saline or HSV Us9-30 mutant. At thirty days post-infection the left corneal epithelium was removed and infected with either saline or wild-type HSV. At forty days post-infection photographs were taken of the mice and the right and left corneas were removed and assayed using FACS analysis.
Results:
Periocular skin lesions were observed in wild-type HSV challenged mice that had not been pre-infected with Us9-30 mutant. Skin lesions were absent in all mice pre-infected with Us9-30 mutant. Corneas infected with Us9-30 mutant had a modest increase in Cd45+ cells compared with corneas treated with saline alone. Corneas of mice infected with wild-type HSV but not exposed to Us9-30 mutant had elevated levels of macrophages, neutrophils, and recruited monocytes. Pre-treatment with Us9-30 mutant reduced the levels of all three immune cell populations following wild-type HSV challenge.
Conclusions:
Ocular infection with Us9-30 mutant reduces the clinical response of subsequent wild-type HSV infection. Us9-30 mutant corneal infection causes an initial subclinical inflammatory response and reduces subsequent immune cell recruitment with later wild-type HSV infection.
Keywords: 545 herpes simplex virus •
557 inflammation •
480 cornea: basic science