ROTAVIRUS CONTAINS INTEGRIN LIGAND SEQUENCES AND A DISINTEGRIN-LIKE DOMAIN THAT ARE IMPLICATED IN VIRUS ENTRY INTO CELLS

Rotavirus contains two outer capsid viral proteins, the spike protein VP4 and major capsid component VP7, both of which are implicated in ce ll entry. We show that VP4 and VP7 contain tripeptide sequences previo usly shown to act as recognition sites far integrins in extracellular matrix proteins. VP4 contains the alpha 2 beta 1 integrin ligand site DGE. In VP7, the alpha x beta 2 integrin ligand site GPR and the alpha 4 beta 1 integrin ligand site LDV are embedded in a novel disintegrin -like domain that also shows sequence similarity to fibronectin and th e tie receptor tyrosine kinase. Microorganism sequence homology to the se ligand motifs and to disintegrins has not been reported previously. In our experiments, peptides including these rotaviral tripeptides an d mAbs directed to these integrins specifically blocked rotavirus infe ction of cells shown to express alpha 2 beta 1 and beta 2 integrins. R otavirus VP4-mediated cell entry may involve the alpha 2 beta 1 integr in, whereas VP7 appears to interact with alpha x beta 2 and alpha 4 be ta 1 integrins.