Evaluation of a theta-defensin in a Murine model of herpes simplex virus type 1 keratitis.
OBJECTIVE
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.
Brandt
Curtis R
CR
Department of Ophthalmology and Visual Science, University of Wisconsin, Madison, WI 53706, USA. crbrandt@facstaff.wisc.edu
Akkarawongsa
Radeekorn
R
Altmann
Sharon
S
Jose
Gilbert
G
Kolb
Aaron W
AW
Waring
Alan J
AJ
Lehrer
Robert I
RI
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D023082:Defensins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D016849:Keratitis, Herpetic / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000627:therapeutic use; D014709:Vero Cells / Q000187:drug effects / Q000821:virology
D000998:Antiviral Agents; D023082:Defensins; D010456:Peptides, Cyclic; C511481:retrocyclin-2, human; C450142:theta-defensin