title: Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition.
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.
authors: From the Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy.
authors: Andrea
authors: A
authors: Civra
authors: the Institute of Sciences of Food Production-National Research Council (ISPA-CNR), c/o Bioindustry Park "SilvanoFumero", 10100 CollerettoGiacosa, Torino, Italy.
authors: Maria Gabriella
authors: MG
authors: Giuffrida
authors: From the Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy.
authors: Manuela
authors: M
authors: Donalisio
authors: the Institute of Sciences of Food Production-National Research Council (ISPA-CNR), c/o Bioindustry Park "SilvanoFumero", 10100 CollerettoGiacosa, Torino, Italy.
authors: Lorenzo
authors: L
authors: Napolitano
authors: the Department of Dermatology and Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Sacramento, California 95817, and.
authors: Yoshikazu
authors: Y
authors: Takada
authors: the Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
authors: Barbara S
authors: BS
authors: Coulson
authors: the Institute of Sciences of Food Production-National Research Council (ISPA-CNR), c/o Bioindustry Park "SilvanoFumero", 10100 CollerettoGiacosa, Torino, Italy.
authors: Amedeo
authors: A
authors: Conti
authors: From the Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy, david.lembo@unito.it.
authors: David
authors: D
authors: Lembo
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D018397:Equidae; D006017:Glycolipids / Q000737:chemistry*; D006023:Glycoproteins / Q000737:chemistry*; D006736:Horses; D006801:Humans; D020128:Inhibitory Concentration 50; D016023:Integrins / Q000737:chemistry; D066292:Lipid Droplets; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008892:Milk; D008894:Milk Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D040901:Proteomics; D012401:Rotavirus / Q000378:metabolism; D012400:Rotavirus Infections / Q000188:drug therapy / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000954:Antigens, Surface; D006017:Glycolipids; D006023:Glycoproteins; D016023:Integrins; C098942:MFGE8 protein, human; D008562:Membrane Glycoproteins; D008894:Milk Proteins; C106215:PAS-6-7 glycoprotein, Bos taurus; D010455:Peptides; C110367:milk fat globule
keywords: RNA virus; antiviral agent; donkey; integrin; lactadherin; milk; peptides; proteomics; rotavirus