To understand the molecular basis of the Cav-1 contribution to influenza A virus propagation we focussed on Cav-1 interactions mediated by the caveolin-scaffolding domain (CSD, aa 81-102) [25] . Database searches and subsequent peptide pull-down assays in combination with co-immunoprecipitation experiments suggested binding of caveolin-1 to M2 presumably to a motif in the M2 protein fitting the CBD consensus [26] . Strikingly, the motif is shared in M2 of nearly all human influenza A viruses. M2 functions within the viral life cycle as a viroporin with proton channel activity that is crucial in the entry phase [1] and as a maturation cofactor in virus budding. The cytoplasmic tail is implicated in M1 binding and facilitates virus assembly and production [2] [3] [4] 35] . Furthermore, Schroeder et al. showed that avian M2 is a cholesterol-binding protein [31] . Most avian influenza A viruses contain two cholesterol recognition motifs (CRAC I, CRAC II) in close vicinity to the transmembrane domain in the cytoplasmic region of M2 [31, 36] . Thus, cholesterol-binding and palmitoylation in combination with a short transmembrane region may direct M2 to the raft periphery in membranes and may promote clustering and merging of rafts which is then followed by the pinching-off of avian viruses [31] . [30] . Notably, to some degree Cav-1 binding to M2 is sensitive to the cholesterol depletion (this investigation). Preliminary results of mutagenesis as well as localization experiments indicate a certain role of the M2-CBD in M2 transport and localization (unpublished observations). Taken together our results demonstrate, that Cav-1 exerts an influence on influenza A virus replication and data imply that the binding of Cav-1 to the matrix protein M2 is involved. However, which function or pathway in MDCK cells actually is triggered via Cav-1 interaction with M2, remains to be determined.