Influenza B virus BM2 protein (BM2)

The Influenza B virus BM2 protein is a type III integral membrane protein essential for viral replication, functioning primarily as a pH-activated proton channel formed by a tetramer of single transmembrane helices that allows proton flux across the viral envelope to facilitate genomic RNA uncoating during entry into host cells. Unlike the unidirectional proton flow of influenza A virus M2 (AM2), BM2 permits bidirectional proton transport due to structural differences, including histidine residues at both ends of the pore, and its channel activity is modulated by pH-induced helical tilting. The protein comprises 109 amino acids, with a 23-residue transmembrane domain and a longer 86-residue cytoplasmic tail critical for additional roles beyond ion conduction, such as binding matrix protein M1 to promote its membrane association, recruiting viral ribonucleoprotein (vRNP) complexes to the plasma membrane, and ensuring proper virion morphology and vRNP packaging during assembly. BM2 knockout mutants fail to produce infectious virus in normal cells, confirming its indispensability, though replication is rescued in BM2-expressing cell lines. In disease contexts, BM2 drives influenza B infection, a key component of seasonal flu, and is proposed as a therapeutic target for novel antivirals since existing M2 inhibitors like amantadine and rimantadine are ineffective against influenza B, necessitating BM2-specific blockers. Structural insights from NMR reveal open and closed states, enabling future drug design to inhibit channel function or assembly roles.

Other names

BM2 proteinInfluenza B M2 protein