High affinity interactions of coxsackievirus A9 with integrin alpha v beta3 (CD51/61) require the CYDMKTTC sequence of beta 3, but do not require the RGD sequence of the CAV-9 VP1 protein

Integrins are transmembrane molecules involved in numerous cell matrix, cel l-cell adhesion phenomena and also utilised as viral receptors. These inter actions with integrins are mediated by brief oligopeptide recognition seque nces. The Arg-Gly-Asp sequence (RGD), is recognized by many integrins, incl uding integrin alpha v beta 3 (CD51/61). Coxsackievirus A9 (CAV-9), a human pathogen that has an Arg-Gly-Asp sequence in the VP1 capsid protein, has b een known to be one of the many viruses that utilise integrin alpha v beta 3 as a receptor. In order to determine important binding sires of CAV-9 on integrin alpha v beta 3, we performed binding studies of CAV-9 on CHO-alpha v beta 3, CHO-alpha v beta 1 and CHO-alpha v beta 1-3-1 mutant cell line, in the presence of function blocking mAb specific for integrin alpha v beta 3 and natural ligand vitronectin. Our experiments show that the CYDMKTTC s equence (187-193 residue) of integrin beta 3, which has been shown to be in volved in ligand specificity, is an important binding site for CAV-9. We al so report that an RGD-less Coxsackievirus A9 mutant can bind efficiently on the ligand binding site of integrin alpha v beta 3. Thus documenting the c apability of this RNA virus to interact with integrin alpha v beta 3, witho ut the presence of an Arg-Gly-Asp sequence. Human Immunology 61, 453-459 (2 000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.