Fusion of the Influenza Virion to the Host Cell Endosome Uncoating of the Influenza Virion Fusion and Uncoating of the Influenza Virion GENE ONTOLOGYGO:0046718 Pubmed0 Pubmed2500008 Pubmed3663665 Pubmed563896 Pubmed8841994 Reactome Database ID Release 43168270 Reactome, http://www.reactome.org ReactomeREACT_6282 Uncoating of viral particles takes place in the host cell endosome. Acidification of the endosome promotes fusion of the viral and endosomal membranes, causing a structural change in the viral hemagglutinin (HA) and freeing the fusion peptide of its HA2 subunit to interact with the endosome membrane. The concerted structural change of several HA molecules opens up a pore through which the viral RNP passes into the cytosol of the cell. The precise timing and the location of uncoating (early vs. late endosomes) depends on the pH-mediated transition of the specific HA molecule involved. The virus-associated M2 ion channel protein allows the influx of H+ ions into the virion, which disrupts protein-protein interactions, resulting in the release of RNP free of the viral M1 matrix protein. Thus the HA mediated fusion of the viral membrane with the endosomal membrane and the M2-mediated release of the RNP results in the release of the RNP complex into the cytosol. Amantadine and rimantadine have been shown to block the ion channel activity of the M2 protein and thus interfere with uncoating. PathwayStep3682 PathwayStep3685