Matrix protein 2 (Influenza A virus) (M2)

Matrix protein 2 (M2) of influenza A virus is a small, integral membrane protein that functions as a proton-selective ion channel (viroporin) and is essential for virus replication. The N-terminal 23-residue ectodomain (M2e) is highly conserved and exposed on the virion surface. M2 enables acidification of the virion interior during endocytosis by selectively transporting protons across the viral envelope in response to endosomal pH, triggering disassembly of ribonucleoproteins from matrix protein 1 and facilitating genome release into the host cell cytoplasm. M2 is also involved in maintaining trans-Golgi network pH, proper maturation of hemagglutinin (HA), efficient virus budding, and interaction with host cellular machinery. The M2 ion channel is targeted by adamantane antivirals, but clinical use is severely limited by widespread resistance. The M2e region is under investigation as a universal influenza A vaccine candidate due to its high conservation, though M2e-targeted vaccines rely on Fc-mediated effector mechanisms and do not provide sterilizing immunity.

Other names

Matrix-2 proteinProton channel protein M2M2 proton channelViroporin M2M2e (for the ectodomain, a subregion)

Blockade of M2 proton channel activity, inhibiting viral uncoating and genome release