Glycoprotein C of herpes simplex virus type 1 is required to cause keratitis at low infectious doses in intact rabbit corneas

Abstract

Purpose. To determine whether the herpes simplex virus type 1 (HSV-1) viral glycoprotein C (gC) plays a role in induction of keratitis in unscarified and scarified rabbit eyes.Materials and methods. A gC deletion mutant (ΔgC) was constructed and then rescued back to wild type (wt) for use as a control. Following ocular infection with each virus in rabbit eyes, with or without prior corneal scarification, keratitis was compared.Results. At low infection doses of 2 × 103 and 2 × 104 plaque-forming units (PFU)/eye, in unscarified cornea, ΔgC produced significantly less keratitis than did wt virus (p = 0.007 and 0.03, respectively). In contrast, the keratitis induced by ΔgC was similar to that induced by the wt virus (p > 0.60) in scarified cornea. At high infection dose (2 × 105 PFU/eye), keratitis induced by ΔgC was similar in scarified and unscarified cornea, and the severity of disease was similar to that seen in scarified eyes at the low-dose ΔgC infections. Interestingly, although ΔgC induced keratitis with or without corneal scarification at high infection doses, the severity of disease was significantly less than that induced by wt infection. At all infection doses, keratitis induced by wt infection was similar in scarified and unscarified eyes.Conclusions. These results suggest that (1) at low infection doses, in unscarified corneas, gC is required for HSV-1 induced keratitis; (2) corneal scarification prior to infection can circumvent the need for gC at low doses, but (3) at higher doses, gC is required for wild-type levels of keratitis even in scarified cornea.