Influenza virus M2 protein is an integral membrane protein expressed on the infected-cell surface.

The influenza A virus M2 protein is expressed abundantly at the cell surface, and in addition to the hemagglutinin (HA) and neuraminidase (NA), is a third virus-specific membrane protein. M2 has an internal hydrophobic membrane anchorage domain and associates with the same cellular membrane fractions as HA and NA. Trypsin treatment of infected cells and immunoprecipitation with site-specific antisera indicate that a minimum of 18 NH2-terminal amino acids of M2 are exposed at the cell surface. Ten NH2-terminal residues are conserved in all strains of influenza A virus for which sequences are available. Antibodies can recognize M2 on the cell surface and therefore it may be an infected-cell surface antigen. We discuss properties of M2 that match it to the elusive major target molecule on influenza A virus-infected cells for cross-reactive cytotoxic T cells.