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

PubMed ID: 17962464

Author(s): Brandt CR, Akkarawongsa R, Altmann S, Jose G, Kolb AW, Waring AJ, Lehrer RI. Evaluation of a theta-defensin in a Murine model of herpes simplex virus type 1 keratitis. Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5118-24. PMID 17962464

Journal: Investigative Ophthalmology & Visual Science, Volume 48, Issue 11, Nov 2007

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.