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United States Department of Agriculture

Agricultural Research Service

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

Authors
item Drolet, Barbara
item Mott, K - UNIV OF CALIF-IRVINE
item Lippa, A - UNIV OF CALIF-IRVINE
item Weschler, S - UNIV OF CALIF-IRVINE
item Perng, G - UNIV OF CALIF-IRVINE

Submitted to: Current Eye Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 22, 2004
Publication Date: August 1, 2004
Citation: Drolet, B.S., Mott, K.R., Lippa, A.M., Weschler, S.L., Perng, G.C. 2004. Glycoprotein c of herpes simplex virus type 1 is required to cause keratitis at low infectious doses in intact rabbit corneas. Current Eye Research. 29(2-3):181-189.

Interpretive Summary: The purpose of this study was to determine whether a specific glycoprotein (gC) of herpes simplex virus type 1 (HSV-1) played a role in the ability of this virus to infect and cause disease in corneas. A gC deletion mutant 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, ocular disease (keratitis) was compared. At low infection doses, the mutant caused significantly less disease in intact corneas compared to the wild type virus. In contrast, the disease induced by the mutant was similar to that induced by the wt virus if the cornea was scratched or scarified prior to infection. At high infectious doses, the mutant infected the unscarified corneas but the disease severity was significantly decreased. 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.

Technical Abstract: 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 (DeltagC) 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 x 10(3) and 2 x 10(4) plaque-forming units (PFU)/eye, in unscarified cornea, DeltagC produced significantly less keratitis than did wt virus (p = 0.007 and 0.03, respectively). In contrast, the keratitis induced by DeltagC was similar to that induced by the wt virus (p > 0.60) in scarified cornea. At high infection dose (2 x 10(5) PFU/eye), keratitis induced by DeltagC was similar in scarified and unscarified cornea, and the severity of disease was similar to that seen in scarified eyes at the low-dose DeltagC infections. Interestingly, although DeltagC 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.

Last Modified: 12/22/2014
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