Identification of Equine Lactadherin-Derived Peptides that Inhibit Rotavirus Infection via Integrin Receptor Competition [Cell Biology]

March 26th, 2015 by Civra, A., Giuffrida, M. G., Donalisio, M., Napolitano, L., Takada, Y., Coulson, B. S., Conti, A., Lembo, D.

Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of five years in both developed and developing countries. Human lactadherin, a milk-fat globule membrane (MFGM) 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 MFGM 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. Since integrin α2β1 plays a critical role during early steps of rotavirus host cell adhesion, we tested a mini-library 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 characterised: pDGE-RGD binds to integrin α2β1 by means of 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.