File:Fimmu-09-01581-g002.jpg

English: Receptor-mediated cell entry of IAVs. (A) Diagram of a bi-antennary N-linked glycan. The terminal sialic acid residues are displayed with an α-2,3 linkage, as well as an α-2,6 linkage, to illustrate the “linear” and “bent” presentations. (B) Illustration of IAV cell entry. (i) IAVs initiate cell entry by using the HA receptor-binding domain (located in the HA1 region) to associate with sialylated glycoconjugates on a host “receptor.” Binding to the “receptor” triggers endocytosis. (ii) The virus then traffics to the endosome where the lower pH facilitates a conformational change in HA, exposing the fusion peptide (located in the HA2 region) for insertion into the endosomal membrane. (iii) The HA pre-hairpin conformation begins to collapse, forming a six-helix bundle that promotes hemifusion of the viral envelop with the endosomal membrane. At some point, the M2 channel opens to release the viral ribonucleoproteins (vRNPs) from M1 by acidifying the viral interior. (iv) HA further collapses into a trimer of hairpins to promote the formation of the fusion pore, which (v) releases the vRNPs into the cytosol. (vi) The exposed nuclear localization signals (NLS) on the vRNPs are recognized by the adaptor protein importin-α, leading to the recruitment of importin-β that (vii) facilitates the transport through the nuclear pore complex (NPC) and into the nucleus.