The virus particle initially associates with a human host cell by binding to sialic acid-containing receptors on the host cell surface. The bound virus is endocytosed by one of four distinct mechanisms. The low endosomal pH sets in motion a number of steps that lead to viral membrane fusion mediated by the viral hemagglutinin (HA) protein, and the eventual release of the uncoated viral ribonucleoprotein complex into the cytosol of the host cell. The ribonucleoprotein complex is transported through the nuclear pore into the nucleus. Once in the nucleus, the incoming negative-sense viral RNA (vRNA) is transcribed into messenger RNA (mRNA) by a primer-dependent mechanism. Replication occurs via a two step process. A full-length complementary RNA (cRNA), a positive-sense copy of the vRNA, is first made and this in turn is used as a template to produce more vRNA. The viral proteins are expressed and processed and eventually assemble with vRNAs at budding sites within the host cell membrane. The viral protein complexes and ribonucleoproteins are assembled into viral particles and bud from the host cell, enveloped in the host cell's membrane.
This release contains a framework for the further annotation of the viral life-cycle.