Influenza virus internal proteins

Influenza virus internal proteins are a collection of highly conserved viral components that are essential for the replication and pathogenesis of the influenza virus [3, 8]. This group includes the viral polymerase complex (PA, PB1, and PB2), the nucleoprotein (NP), matrix proteins (M1 and M2), and non-structural proteins (NS1 and NEP) [4, 6]. Unlike the surface glycoproteins hemagglutinin and neuraminidase, which undergo frequent antigenic drift, these internal proteins remain relatively stable across different strains and subtypes [19, 20]. They facilitate critical stages of the viral life cycle, such as uncoating in the endosome via the M2 ion channel, genome replication in the nucleus, and evasion of the host's innate immune system by the NS1 protein [2, 10]. Therapeutic agents targeting these proteins include M2 ion channel blockers like amantadine and polymerase inhibitors like baloxavir marboxil [7, 12]. Additionally, these proteins are primary targets for the development of universal T-cell-based vaccines due to their high conservation and ability to induce robust CD8+ T-cell responses [11, 19]. However, the clinical utility of many existing drugs is challenged by the rapid emergence of resistant viral variants, particularly within the M2 protein [10, 15].

Other names

Internal viral proteinsConserved influenza proteinsInfluenza core proteinsInfluenza virus internal antigens

Inhibition of viral uncoating via M2 channel blockade, inhibition of viral mRNA synthesis via cap-dependent endonuclease inhibition, and inhibition of viral genome replication via RNA-dependent RNA polymerase or nucleoprotein interference.