High affinity interactions of Coxsackievirus A9 with integrin alphavbeta3 (CD51/61) require the CYDMKTTC sequence of beta3, but do not require the RGD sequence of the CAV-9 VP1 protein.
Integrins are transmembrane molecules involved in numerous cell matrix, cell-cell adhesion phenomena and also utilised as viral receptors. These interactions with integrins are mediated by brief oligopeptide recognition sequences. The Arg-Gly-Asp sequence (RGD), is recognized by many integrins, including integrin alphavbeta3 (CD51/61). Coxsackievirus A9 (CAV-9), a human pathogen that has an Arg-Gly-Asp sequence in the VP1 capsid protein, has been known to be one of the many viruses that utilise integrin alphavbeta3 as a receptor. In order to determine important binding sites of CAV-9 on integrin alphavbeta3, we performed binding studies of CAV-9 on CHO-alphavbeta3, CHO-alphavbeta1 and CHO-alphavbeta1-3-1 mutant cell line, in the presence of function blocking mAb specific for integrin alphavbeta3 and natural ligand vitronectin. Our experiments show that the CYDMKTTC sequence (187-193 residue) of integrin beta3, which has been shown to be involved in ligand specificity, is an important binding site for CAV-9. We also report that an RGD-less Coxsackievirus A9 mutant can bind efficiently on the ligand binding site of integrin alphavbeta3. Thus documenting the capability of this RNA virus to interact with integrin alphavbeta3, without the presence of an Arg-Gly-Asp sequence.
Triantafilou
M
M
Department of Biological Sciences, University of Essex, Colchester, Essex, United Kingdom.
Triantafilou
K
K
Wilson
K M
KM
Takada
Y
Y
Fernandez
N
N
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D004770:Enterovirus; D039564:Integrin alphaV; D039661:Integrin beta3; D009842:Oligopeptides / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011485:Protein Binding
D015703:Antigens, CD; D036022:Capsid Proteins; D039564:Integrin alphaV; D039661:Integrin beta3; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; C047981:arginyl-glycyl-aspartic acid