1. Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition*
- Author
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Civra, Andrea, Giuffrida, Maria Gabriella, Donalisio, Manuela, Napolitano, Lorenzo, Takada, Yoshikazu, Coulson, Barbara S, Conti, Amedeo, and Lembo, David
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Pediatric ,Infectious Diseases ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Infection ,Amino Acid Motifs ,Amino Acid Sequence ,Animals ,Antigens ,Surface ,Cattle ,Cell Membrane ,Cell Survival ,Equidae ,Glycolipids ,Glycoproteins ,Horses ,Humans ,Inhibitory Concentration 50 ,Integrins ,Lipid Droplets ,Membrane Glycoproteins ,Milk ,Milk Proteins ,Molecular Sequence Data ,Peptides ,Proteomics ,Rotavirus ,Rotavirus Infections ,Sequence Homology ,Amino Acid ,Spectrometry ,Mass ,Matrix-Assisted Laser Desorption-Ionization ,antiviral agent ,integrin ,peptides ,proteomics ,RNA virus ,donkey ,lactadherin ,milk ,rotavirus ,Chemical Sciences ,Medical and Health Sciences ,Biochemistry & Molecular Biology ,Biological sciences ,Biomedical and clinical sciences ,Chemical sciences - Abstract
Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of 5 years in both developed and developing countries. Human lactadherin, a milk fat globule membrane glycoprotein, inhibits human rotavirus infection in vitro, whereas bovine lactadherin is not active. Moreover, it protects breastfed infants against symptomatic rotavirus infections. To explore the potential antiviral activity of lactadherin sourced by equines, we undertook a proteomic analysis of milk fat globule membrane proteins from donkey milk and elucidated its amino acid sequence. Alignment of the human, bovine, and donkey lactadherin sequences revealed the presence of an Asp-Gly-Glu (DGE) α2β1 integrin-binding motif in the N-terminal domain of donkey sequence only. Because integrin α2β1 plays a critical role during early steps of rotavirus host cell adhesion, we tested a minilibrary of donkey lactadherin-derived peptides containing DGE sequence for anti-rotavirus activity. A 20-amino acid peptide containing both DGE and RGD motifs (named pDGE-RGD) showed the greatest activity, and its mechanism of antiviral action was characterized; pDGE-RGD binds to integrin α2β1 by means of the DGE motif and inhibits rotavirus attachment to the cell surface. These findings suggest the potential anti-rotavirus activity of equine lactadherin and support the feasibility of developing an anti-rotavirus peptide that acts by hindering virus-receptor binding.
- Published
- 2015