Biochemical and structural analyses of interactions between viruses and their cognate IgSF receptors reveal several striking similarities. First, in cases in which structural information about virus-receptor complexes is available, the viral attachment proteins exclusively bind to the most membrane-distal, N-terminal domain (D1) of the IgSF receptors [3] [4] [5] [6] [7] [8] [9] [10] . While structural information about com-plex formation is lacking for the IgSF receptors carcinoembryonic antigen-related cell adhesion molecule, nectin-1, nectin-2, and signaling lymphocyte-activation molecule (SLAM), biochemical studies also implicate their respective D1 domains in virus binding [11] [12] [13] [14] . Second, viruscontacting residues lie towards the upper ''tip'' of the IgSF D1 domain. Third, the viral receptor-binding region engages the CC9FG b-sheet of the IgSF receptor D1 domain. Fourth and finally, almost all of the receptor domains interacting with viruses belong to the V-type IgSF fold. The single exception, the D1 domain of ICAM-1, belongs to the I-set type, which is structurally similar to the V-set domain.