In order to elucidate the molecular basis of the interaction we scanned influenza A virus proteins for putative binding motifs. Cav-1 binds to various cellular proteins like membrane receptors, soluble or membrane-associated molecules [24] as well as several viral proteins and exerts functions in localisation, transport and cellular signalling (Table 1 ). Signalling is preceded by phosphorylation of Cav-1, which initiates events leading either to activation of specific signalling pathways [21] or maintenance of signalling-competent, yet inactive complexes [24] . A specific, lumenal domain termed caveolin scaffolding domain (CSD, aa 82-101) which resides adjacent to the region of membrane insertion, is responsible for specific protein binding in the vast majority of cases [24, 25] . Two consensus sequences have been identified in phage-display experiments and in the primary structure of Cav-1 binding partners which were termed caveolin binding domains (CBD) [26] . CBDs have been recognized in cellular [24] and viral proteins ( Table 1 ). The consensus sequence comprises a run of 3 aromatic residues (W, F, Y) separated by a characteristic spacing (ΦxxxxΦxxΦ; ΦxΦxxxxΦ; where x stands for any amino acid and Φ for W, F, Y). Our screening for CBDs identified putative binding regions in HA, PB2 and M2 of influenza A virus. Especially, a region in the M2 channel protein turned out to be highly conserved among human influenza A viruses (Fig. 3B ). The putative CBD overlaps with a loop/helical domain immediately following the M2 transmembrane region at the lumenal site of M2 (Fig. 3A) . The CBD surrounds Cys 50, which is palmitoylated and faces the membrane allowing for insertion of the palmitoyl residue into the lipid bilayer. Thus, the CBD would be located favourably for interaction with the Cav-1 scaffolding domain [27, 28] . Strikingly, compared to M2 of A/PR8/34 as a reference the CDB core motif (positions F47, Y52, F55) and immediately adjacent amino acid residues are completely conserved in 8 M2 sequences available for the pandemic influenza virus of swine origin A/2009 (H1N1) (Fig. 3C) . Furthermore, motif conservation is observed in a former H1N1 strain appearing in 1977, but homology is restricted to the aromatic core and to a lesser extent to adjacent residues. Surprisingly, in M2 of influenza A/ 1918 the CBD motif is not conserved, as its third aromatic residue phenylalanine is changed to leucine, a residue commonly found in the M2 of avian influenza A viruses at that position (G.-V. Hemgård and M. Wirth, unpublished observation).