Influenza virus M2 protein and haemagglutinin conformation changes during intracellular transport.

The influenza virus M2 protein has an ion channel activity that permits ions to enter the virion during its uncoating and also modulates pH of intracellular compartments. M2 protein is a homotetramer consisting of either a pair of disulfide-linked dimers or a disulfide-linked tetramer. The M2 trans-membrane domain peptide adopts an alfa helical secondary structure. In polarized cells, M2 protein is expressed at the apical cell surface. The amantadine-induced, M2-mediated conversion of influenza A virus haemagglutinin (HA) to the low pH conformation occurs in an acidic trans-Golgi compartment. The M2 protein ion channel activity can affect the conformation of cleaved HA during intracellular transport. The equine influenza virus 1 HA expressed from cDNA does not require coexpression of a functional M2 protein to maintain HA in its native conformation.