Cell-surface interactions of echovirus 22.
Echovirus 22 (EV22) is a picornavirus forming a distinct molecular cluster together with echovirus 23. EV22 has an Arg-Gly-Asp (RGD) peptide motif in its capsid protein VP1; similar motifs are known to mediate many cell-cell and microbe-host interactions. To identify peptide sequences that specifically bind to EV22 and potentially play a role in receptor recognition, we have used here peptide libraries displayed in filamentous phage. We isolated an EV22-binding motif CLRSG(R/F)GC. The synthetic CLRSGRGC peptide was able to inhibit EV22 infection. The infection was also inhibited by an RGD-containing peptide representing the C terminus of the EV22 capsid protein VP1 and CWDDGWLC (an RGD-binding peptide; Pasqualini, R., Koivunen, E., and Ruoslahti, E. (1995) J. Cell Biol. 130, 1189-1196). As the EV22-recognizing sequence LRSG is found in the integrin beta1 chain and the entire LRSGRG hexapeptide occurs in the matrix metalloproteinase 9 (MMP-9), we carried out blocking experiments with anti-integrin and anti-MMP-9 antibodies. EV22 infection could be blocked in cell cultures with anti-alphav, -beta1, and, to a lesser extent, with anti-MMP-9 antibodies. These results imply that EV22 recognizes preferentially alphavbeta1-integrin as a cellular receptor and MMP-9 may also play a role in the cell-surface interactions of the virus.
Pulli
T
T
National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. timo.pulli@ktl.fi
Koivunen
E
E
Hyypiä
T
T
D000595:Amino Acid Sequence; D002213:Capsid / Q000737:chemistry*; D017364:Collagenases / Q000502:physiology; D016384:Consensus Sequence; D004770:Enterovirus / Q000737:chemistry* / Q000254:growth & development; D029822:Enterovirus B, Human / Q000737:chemistry* / Q000254:growth & development; D006801:Humans; D007158:Immunologic Techniques; D016023:Integrins / Q000502:physiology; D020780:Matrix Metalloproteinase 9; D008969:Molecular Sequence Data; D009842:Oligopeptides; D019151:Peptide Library; D011991:Receptors, Virus / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D016023:Integrins; D009842:Oligopeptides; D019151:Peptide Library; D011991:Receptors, Virus; C047981:arginyl-glycyl-aspartic acid; D017364:Collagenases; D020780:Matrix Metalloproteinase 9