Integrin-using rotaviruses bind MA104 cell surface
alpha2beta1 integrin via the
Asp-Gly-Glu (DGE) sequence in virus spike
protein VP4 and interact with
alphaxbeta2 integrin during cell entry through outer
capsid protein VP7.
Infection is inhibited by the alpha2beta1
ligand Asp-Gly-Glu-Ala (DGEA) and the alphaxbeta2
ligand Gly-Pro-Arg-Pro (GPRP), and virus-alpha2beta1 binding is increased by alpha2beta1 activation. In this study, we analyzed the effects of monomers and
polymers containing DGEA-, GPRP-, and DGEA-related
peptides on rotavirus binding and
infection in intestinal (Caco-2) and kidney (MA104) cells and virus binding to recombinant alpha2beta1. Blockade of rotavirus-cell binding and
infection by
peptides and anti-alpha2 antibody showed that Caco-2 cell entry is dependent on virus binding to alpha2beta1 and interaction with alphaxbeta2. At up to 0.5 mM, monomeric DGEA and DGAA inhibited binding to alpha2beta1 and
infection. At higher concentrations, DGEA and DGAA showed a reduced ability to inhibit virus-cell binding and
infection that depended on virus binding to alpha2beta1 but occurred without alteration in cell surface expression of alpha2, beta2, or
alphavbeta3 integrin. This loss of DGEA activity was abolished by
genistein treatment and so was dependent on
tyrosine kinase signaling. It is proposed that this signaling activated existing cell surface alpha2beta1 to increase virus-cell attachment and entry. Polymeric
peptides containing DGEA and GPRP or GPRP only were inhibitory to SA11
infection at approximately 10-fold lower concentrations than
peptide monomers. As polymerization can improve
peptide inhibition of
virus-receptor interactions, this approach could be useful in the development of inhibitors of receptor recognition by other viruses.