Figure 1.

Overview of the influenza virus entry and replication process. In the inset on the right, the different virion components are specified. (a) After binding of the viral HA to sialylated glycans on the host cell surface, the virus is internalized by endocytosis. (b) Acidification of the endosome leads to activation of the M2 proton channel and virion acidification, resulting in virus uncoating (i.e., dissociation of the vRNPs from the M1 capsid protein). The low pH inside the endosome also triggers a conformational change in the HA, leading to fusion of the viral and endosomal membranes. After vRNP release in the cytoplasm and dissociation of residual M1, nuclear localization signals in NP direct the transport of the vRNPs into the nucleus. (c) In the nucleus, the viral polymerase starts mRNA synthesis by cleaving off 5′‐capped RNA fragments from host cell pre‐mRNAs. Then, viral mRNA transcription is initiated from the 3′ end of the cleaved RNA cap. (d) Viral mRNAs are transported to the cytoplasm for translation into viral proteins. HA, M2, and NA are processed in the endoplasmic reticulum and the Golgi apparatus, and subsequently transported to the cell membrane. (e) Besides viral mRNA synthesis, the viral polymerase performs the unprimed replication of vRNAs. The vRNAs are first transcribed into positive‐stranded cRNAs, which then function as the template for the synthesis of new vRNAs. During their synthesis, vRNAs and cRNAs are encapsidated by NPs. Export of the newly formed vRNPs into the cytoplasm is mediated by an M1‐NS2 complex that is bound to the vRNPs. (f) As they reach the cell membrane, the vRNPs associate with viral glycoproteins at the plasma membrane from which new virions bud off. Finally, the NA cleaves the sialic acid termini on viral and cell membrane glycoproteins, thereby releasing the progeny virions from the host cell.