Evaluation of a theta-defensin in a Murine model of herpes simplex virus type 1 keratitis
| Autor: | Alan J. Waring, Curtis R. Brandt, Radeekorn Akkarawongsa, Sharon Altmann, Robert I. Lehrer, Gilbert G. Jose, Aaron W. Kolb |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
viruses
Herpesvirus 1 Human Biology medicine.disease_cause Antiviral Agents Peptides Cyclic Theta defensin Herpesviridae Virus Keratitis Defensins Mice In vivo Chlorocebus aethiops medicine Animals Defensin Vero Cells Cell Proliferation Virus quantification Mice Inbred BALB C medicine.disease Virology Disease Models Animal Herpes simplex virus Keratitis Herpetic Female |
| Zdroj: | Investigative ophthalmologyvisual science. 48(11) |
| ISSN: | 0146-0404 |
| Popis: | PURPOSE. To test the activity of a synthetic -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 EC50 of 10 M( 20 g/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. (Invest Ophthalmol Vis Sci. 2007;48: 5118‐5124) DOI:10.1167/iovs.07-0302 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|