Evaluation of a theta-defensin in a Murine model of herpes simplex virus type 1 keratitis.

Abstract

PURPOSE:

To test the activity of a synthetic theta-defensin, retrocyclin (RC)-2, in a murine herpes simplex virus (HSV)-1 keratitis model.

METHODS:

The in vitro antiviral activity of RC-2 against HSV-1 KOS was determined by yield reduction and viral inactivation assays. Efficacy in an experimental murine HSV-1 keratitis model was tested using pre- or postinfection treatment with 0.1% peptide in PBS with or without 2% methylcellulose. Viral titers in the tear film were determined by plaque assay.

RESULTS:

RC-2 inhibited HSV-1 KOS in vitro with an EC(50) of 10 microM (~20 microg/mL) in yield-reduction assays, but was not directly virucidal. RC-106 (a less active analogue) did not inhibit HSV-1 KOS in culture. Incubating the virus with RC-2 or applying the peptide in 2% methylcellulose to the cornea before viral infection significantly reduced the severity of ocular disease, but postinfection treatment with 0.1% RC-2 in PBS with or without 2% methylcellulose did not. Viral titers were significantly reduced on some days after infection in the preincubation and prophylaxis groups.

CONCLUSIONS:

RC-2 was active against HSV-1 KOS in cultures and showed protective activity in vivo when used in a prophylactic mode, but the peptide showed limited activity in a postinfection herpes keratitis model. These findings support data obtained from experiments with HIV-1, HSV-2, and influenza A, indicating that RCs inhibit the entry of viruses rather than their replication.

• Authors: Curtis R Brandt, Radeekorn Akkarawongsa, Sharon Altmann, Gilbert Jose, Aaron W Kolb, Alan J Waring, Robert I Lehrer
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 48 Issue 11 Pg. 5118-24 (Nov 2007) ISSN: 0146-0404 [Print] United States
• PMID: 17962464 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• Defensins
• Peptides, Cyclic
• retrocyclin-2, human
• theta-defensin

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Cell Proliferation (drug effects)
• Chlorocebus aethiops
• Defensins (therapeutic use)
• Disease Models, Animal
• Female
• Herpesvirus 1, Human (drug effects, physiology)
• Keratitis, Herpetic (prevention & control)
• Mice
• Mice, Inbred BALB C
• Peptides, Cyclic (therapeutic use)
• Vero Cells (drug effects, virology)