Table 1.

Summary of the functions and interactions of the proteins coded by each RNA segment of influenza viruses (aas, amino acids).

RNA Segment	Protein(s) Coded	Function [20,31,35]	Structural Data [20,31,35,36]
1	PB2 759 aas	Located in the nucleus of infected cells; Signals the viral polymerase passage to the host’s nucleus; Enhances the formation of the cap structures necessary for viral messenger RNA (mRNA) transcription; Located in the mitochondria of infected cells [37]; Inhibits Interferon-β; Helps determine host range.	The three proteins, PB2 (polymerase basic protein 2), PB1 (polymerase basic protein 1) and PA (polymerase acidic protein), form the viral RNA polymerase, responsible for viral RNA transcription and replication.
2	PB1 757 aas	Responsible for the elongation of the primed nascent viral mRNA; Located in the nucleus of infected cells; Enhances the association of the 3 subunits of the RNA polymerase complex.
3	PA 716 aas	Functions still unknown, but evidence points to helicase-like functions; Important for viral transcription; Assembly of the polymerase complex.
4	HA 550 aas	Attaches the virions to the sialic acid (SA) moieties of the host’s receptors; Around 30% variation between subtypes.	Hemagglutinin (HA) is a homotrimeric integral cylinder-like membrane glycoprotein on the virus surface; 4 antigenic sites with direct impact on virulence and pathogenicity of the virus.
5	NP 498 aas	Binds non-specifically to single-stranded RNA (ssRNA); Encapsidates viral RNA; Helps recruiting RNA polymerase for synthesis of viral positive-sense RNA (cRNA); Related to host range.	Nucleoprotein (NP) is a 56 kDa basic protein; RNA-binding protein; Structural unit of RNPs; Forms oligomers stabilized by vRNA.
6	NA 470 aas	Unnecessary for virus replication; Required for budding of newly formed viral particles from surface of infected cells; Facilitates virus movement to the target cell by cleavage of sialic acids from respiratory tract mucins; Helps the release of virions from infected cells.	Neuraminidase (NA) is a homotetrameric integral membrane glycoprotein with 4 structural domains; Antigenic sites help circumvent the immune responses aiding on the virulence and pathogenicity of the virus.
7	M1 252 aas	Membrane-binding and RNA-binding protein; Forms a coat inside the viral envelope; Determines virion’s shape; Interacts with vRNP and other cytoplasmic domains of integral membrane proteins; Increases vRNPs export and decreases import; Helps assembly and budding of virions.	Matrix protein (M1) formed by a globular N-terminal domain and a flexible C-terminal tail; Oligomerization state and binding to lipid bilayer are highly dependent on pH.
	M2 97 aas	Vital for viral replication; Forms proton channel in virus envelope; Lowers the pH inside the viral particle to promote uncoating of RNPs; Modulates Golgi’s pH; Helps to stabilize HA’s native conformation during virus assembly.	Matrix-2 protein (M2) is a 97-residue single-pass membrane protein; Three segments: N-terminal outward segment, transmembrane (TM) helix, and C-terminal inward segment; TM helices from 4 subunits pack to form proton-channel; Highly conserved His37 and Trp41 residues.
8	NS1 230 aas	NS1 acts as a promoter of viral replication and an inhibitor of the host’s immune response; Present in the cytoplasm and nucleus of the host cell.	Non-structural protein 1 (NS1) has two structural domains—RNA-binding domain (RBD) and the effector domain (ED)—connected by a short linker (LR), and a disordered C-terminal tail (CTT).
	NEP/NS2 121 aas	Promotes viral RNA replication; Regulates vRNP’s export from the nucleus to the cytoplasm; RNA nuclear export; Interacts with the viral matrix M1 protein.	Nuclear Export Protein (NEP) has a protease-sensitive N-terminal domain (residues 1–53) and a protease-resistant C-terminal domain (residues 54–121) mostly formed by a helical hairpin.