Although the database of viral proteins in complex with IgSF receptors is still quite small, interactions of viruses with their receptors parallel the recognition mode of immunoglobulins, which also recognize their cognate antigens via residues at the tip of their N-terminal, V-set domains. The case of the receptor-binding head domain of reovirus attachment protein s1 in complex with the D1 domain of its receptor, junctional adhesion molecule-A (JAM-A) [9] , serves to illustrate this point ( Figure 1A ). The JAM-A homodimer strikingly resembles the dimer formed by the V-set domains of the light and heavy chains of immunoglobulins. In both structures, the two V-set domains face each other with similar orientations. Moreover, residues in the receptor required for virus attachment reside in bstrands and intervening loops that juxta-pose the complementarity determining regions (CDRs) of antibody molecules. Thus, residues known to interact with ligands map to corresponding regions near the tip and one side of the V-set domains. These similarities extend beyond reovirus receptor JAM-A. Other IgSF virus receptors, such as the coxsackievirus and adenovirus receptor (CAR) [5] and HIV receptor CD4 [4] , also recognize their viral ligands via residues that partially overlap with the CDR region of immunoglobulins ( Figure 1B -F). CAR forms a homodimer via its D1 domain that is very similar to the JAM-A homodimer [15] . CD4 also forms homodimers, albeit via its D4 domain [16] .