Influenza A viruses are enveloped, negative strand RNA viruses belonging to the Orthomyxoviridae family. Their genome consists of eight single-stranded RNA segments encoding 11 or 12 proteins: the receptor-binding haemagglutinin (HA); the sialic acid-destroying enzyme neuraminidase (NA), the ion channel M2, the matrix protein M1; the nucleoprotein (NP); the polymerase acidic protein (PA), polymerase basic proteins 1 and 2 (PB1, PB2) and the pro-apoptotic protein polymerase basic 1 (PB1)-F2; the nuclear export protein (NEP; also known as NS2) and the host antiviral response antagonist non-structural protein 1 (NS1); the newly identified N40 protein, which is expressed from the PB1 segment and has an unknown function [77]. Within the virion, each of the eight RNA segments forms a viral ribonucleoprotein (RNP) complex: in particular, viral RNA is wrapped around NP, and this structure is in turn bound to the viral polymerase complex, to constitute the viral nucleocapsid. In the initial stages of influenza A virus replication, the viral HA binds to host cell receptors that contain terminal α-2,6-linked or α-2,3-linked sialic acid (α-2,6-SA or α-2,3-SA) moieties, and the virus enters the cell by receptor-mediated endocytosis. Cleavage of HA by cellular proteases is required to expose the HA peptide that is responsible for the fusion between the viral envelope and the endosomal membrane. Acidification of the late endocytic vesicles allows the viral HA to undergo a conformational rearrangement that produces a fusogenic protein. The H+ ions in the acidic endosome are pumped, via the viral M2 ion channel, into the virus structure allowing the virus uncoating and the release of RNP complexes into the cytoplasm. The viral RNA is then imported in an ATP-dependent manner into the cell nucleus for transcription of genomic and messenger RNAs which are transported to the cytosol for translation. Viral HA, NA and M2 are synthesized in the Endoplasmic Reticulum, transported by the trans-Golgi secretory pathway and the mature proteins are inserted in the plasma membrane. New viral RNA is encased in the nucleocapsidic proteins and, together with matrix protein, is transported to cell surface where HA and NA will be incorporated. Progeny virions are then released from cells by budding.
Giovanna De Chiara, Maria Elena Marcocci, Rossella Sgarbanti, Livia Civitelli, Cristian Ripoli, Roberto Piacentini, Enrico Garaci, Claudio Grassi, Anna Teresa Palamara
CC BY 2.5
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