A Cationic TAT Peptide Inhibits Herpes Simplex Virus Type 1 Infection of Human Corneal Epithelial Cells

Abstract

Abstract

Purpose:

To determine if a peptide, TAT-Cd⁰, inhibits Herpes simplex virus type 1 infection of human corneal epithelial cells.

Methods:

TAT-Cd⁰ and a control peptide, E_50,51TAT-Cd⁰, were added at various times throughout infection with the lacz-expressing hrR3 virus, and viral replication was measured by β-galactosidase activity. Toxicity was assessed using a dye reduction assay.

Results:

The CC₅₀ value for TAT-Cd⁰ was ∼100 μM. In assays with peptide present at all times, TAT-Cd⁰ was 150-fold more active than E_50,51TAT-Cd⁰ (EC₅₀ 0.2 vs. 30.0 μM). The EC₅₀ values of TAT-Cd⁰ for entry inhibition, cell protection, virus inactivation, and inhibition of attachment were 0.1, 0.4, 9.5, and 3.0 μM, respectively. TAT-Cd⁰ was less effective when added 1 h postinfection (EC₅₀ = 30.0 μM).

Conclusions:

TAT-Cd⁰ is an effective inhibitor of Herpes simplex virus type 1 infection in human corneal epithelial cells and affects multiple steps before, or very early, in infection. The peptide has potential as an antiviral and further studies are warranted.