Modified host defence peptide GF19 slows TNT-mediated spread of corneal herpes simplex virus serotype I infection

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Publicat a:	Scientific Reports (Nature Publisher Group) vol. 14, no. 1 (2024), p. 4096
Autor principal:	Thathapudi, Neethi C.
Altres autors:	Callai-Silva, Natalia, Malhotra, Kamal, Basu, Sankar, Aghajanzadeh-Kiyaseh, Mozhgan, Zamani-Roudbaraki, Mostafa, Groleau, Marc, Lombard-Vadnais, Félix, Lesage, Sylvie, Griffith, May
Publicat:	Nature Publishing Group
Matèries:	Infections Cytotoxicity Nanoparticles Cornea Chemokines Herpes simplex Controlled release Peptides Herpes viruses Biological activity Epithelium Immunosuppressive agents Epithelial cells Antiviral agents Nanotubes Nanotechnology Amino acids Silica Mode of action Antiviral drugs Environmental
Accés en línia:	Citation/Abstract Full Text - PDF
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022			\|a 2045-2322
024	7		\|a 10.1038/s41598-024-53662-4 \|2 doi
035			\|a 2928442951
045	2		\|b d20240101 \|b d20241231
084			\|a 274855 \|2 nlm
100	1		\|a Thathapudi, Neethi C. \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); Université de Montréal, Institute of Biomedical Engineering, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
245	1		\|a Modified host defence peptide GF19 slows TNT-mediated spread of corneal herpes simplex virus serotype I infection
260			\|b Nature Publishing Group \|c 2024
513			\|a Journal Article
520	3		\|a 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.
653			\|a Infections
653			\|a Cytotoxicity
653			\|a Nanoparticles
653			\|a Cornea
653			\|a Chemokines
653			\|a Herpes simplex
653			\|a Controlled release
653			\|a Peptides
653			\|a Herpes viruses
653			\|a Biological activity
653			\|a Epithelium
653			\|a Immunosuppressive agents
653			\|a Epithelial cells
653			\|a Antiviral agents
653			\|a Nanotubes
653			\|a Nanotechnology
653			\|a Amino acids
653			\|a Silica
653			\|a Mode of action
653			\|a Antiviral drugs
653			\|a Environmental
700	1		\|a Callai-Silva, Natalia \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); Université de Montréal, Institute of Biomedical Engineering, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
700	1		\|a Malhotra, Kamal \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); University of Ottawa, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Canada (GRID:grid.28046.38) (ISNI:0000 0001 2182 2255); University of Ottawa, Department of Cellular and Molecular Medicine, Ottawa, Canada (GRID:grid.28046.38) (ISNI:0000 0001 2182 2255)
700	1		\|a Basu, Sankar \|u Asutosh College, (Affiliated With University of Calcutta), Department of Microbiology, Kolkata, India (GRID:grid.59056.3f) (ISNI:0000 0001 0664 9773)
700	1		\|a Aghajanzadeh-Kiyaseh, Mozhgan \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); Université de Montréal, Institute of Biomedical Engineering, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
700	1		\|a Zamani-Roudbaraki, Mostafa \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); Université de Montréal, Institute of Biomedical Engineering, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
700	1		\|a Groleau, Marc \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); Université de Montréal, Département de Microbiologie, Infectiologie et Immunologie, Montréal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
700	1		\|a Lombard-Vadnais, Félix \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666)
700	1		\|a Lesage, Sylvie \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Département de Microbiologie, Infectiologie et Immunologie, Montréal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
700	1		\|a Griffith, May \|u Maisonneuve-Rosemont Hospital Research Centre, Montreal, Canada (GRID:grid.414216.4) (ISNI:0000 0001 0742 1666); Université de Montréal, Department of Ophthalmology, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136); Université de Montréal, Institute of Biomedical Engineering, Montreal, Canada (GRID:grid.14848.31) (ISNI:0000 0001 2104 2136)
773	0		\|t Scientific Reports (Nature Publisher Group) \|g vol. 14, no. 1 (2024), p. 4096
786	0		\|d ProQuest \|t Science Database
856	4	1	\|3 Citation/Abstract \|u https://www.proquest.com/docview/2928442951/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch
856	4	0	\|3 Full Text - PDF \|u https://www.proquest.com/docview/2928442951/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch