Influenza A virus matrix protein 2 (M2)

The influenza A virus matrix protein 2 (M2) is a small, 97-amino acid integral membrane protein that assembles as a homotetramer in the viral envelope, forming a proton-selective ion channel (viroporin)[1][5][6]. Its activity is crucial for the viral life cycle: during host cell entry, the low pH of the endosome activates the channel, allowing protons to enter the viral core, which triggers dissociation of matrix proteins from viral RNA and facilitates uncoating[1][2][3]. The M2 channel also maintains the appropriate pH for hemagglutinin function during viral maturation in the trans-Golgi network[2][4]. Structurally, the M2 channel has three domains: an extracellular N-terminal, a transmembrane helix (the pore), and a cytoplasmic tail involved in assembly and membrane scission[1][3]. Drugs like amantadine and rimantadine block the channel, but widespread resistance due to TM domain mutations has limited their use[1][2][3]. The M2 protein serves as a key drug target in influenza infection, but is also notable for its role in drug resistance and as a molecular marker for viral subtyping. If you need mapping to other influenza virus M2-like proteins (BM2, CM2 in influenza B and C), note that these differ substantially in sequence but share the same general function[1].

Other names

M2 proteinInfluenza A M2M2 proton channelMatrix-2 protein

Drugs such as amantadine and rimantadine inhibit the proton channel, blocking acidification and preventing viral uncoating and replication.