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 crossreactive cytotoxic T cells.