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Modified host defence peptide GF19 slows TNT-mediated spread of corneal herpes simplex virus serotype I infection.
Thathapudi, Neethi C; Callai-Silva, Natalia; Malhotra, Kamal; Basu, Sankar; Aghajanzadeh-Kiyaseh, Mozhgan; Zamani-Roudbaraki, Mostafa; Groleau, Marc; Lombard-Vadnais, Félix; Lesage, Sylvie; Griffith, May.
Afiliación
  • Thathapudi NC; Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, H1T 2M4, Canada.
  • Callai-Silva N; Department of Ophthalmology, Université de Montréal, Montreal, QC, H3C 3J7, Canada.
  • Malhotra K; Institute of Biomedical Engineering, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
  • Basu S; Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, H1T 2M4, Canada.
  • Aghajanzadeh-Kiyaseh M; Department of Ophthalmology, Université de Montréal, Montreal, QC, H3C 3J7, Canada.
  • Zamani-Roudbaraki M; Institute of Biomedical Engineering, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
  • Groleau M; Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, H1T 2M4, Canada.
  • Lombard-Vadnais F; Department of Ophthalmology, Université de Montréal, Montreal, QC, H3C 3J7, Canada.
  • Lesage S; Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, University of Ottawa, Ottawa, K1Y 4W7, Canada.
  • Griffith M; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada.
Sci Rep ; 14(1): 4096, 2024 02 19.
Article en En | MEDLINE | ID: mdl-38374240
ABSTRACT
Corneal HSV-1 infections are a leading cause of infectious blindness globally by triggering tissue damage due to the intense inflammation. HSV-1 infections are treated mainly with antiviral drugs that clear the infections but are inefficient as prophylactics. The body produces innate cationic host defence peptides (cHDP), such as the cathelicidin LL37. Various epithelia, including the corneal epithelium, express LL37. cHDPs can cause disintegration of pathogen membranes, stimulate chemokine production, and attract immune cells. Here, we selected GF17, a peptide containing the LL37 fragment with bioactivity but with minimal cytotoxicity, and added two cell-penetrating amino acids to enhance its activity. The resulting GF19 was relatively cell-friendly, inducing only partial activation of antigen presenting immune cells in vitro. We showed that HSV-1 spreads by tunneling nanotubes in cultured human corneal epithelial cells. GF19 given before infection was able to block infection, most likely by blocking viral entry. When cells were sequentially  exposed to viruses and GF19,  the infection was attenuated but not arrested, supporting the contention that the GF19 mode of action was to block viral entry. Encapsulation into silica nanoparticles allowed a more sustained release of GF19, enhancing its activity. GF19 is most likely suitable as a prevention rather than a virucidal treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Herpesvirus Humano 1 / Herpes Simple Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Herpesvirus Humano 1 / Herpes Simple Límite: Humans Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido