Wohlgemuth N, Lane AP, Pekosz A. Influenza A Virus M2 Protein Apical Targeting Is Required for Efficient Virus Replication. J Virol. 2018 Oct 29;92(22).
The influenza A virus (IAV) M2 protein is a multifunctional protein with critical roles in virion entry, assembly, and budding. M2 is targeted to the apical plasma membrane of polarized epithelial cells, and the interaction of the viral proteins M2, M1, HA, and NA near glycolipid rafts in the apical plasma membrane is hypothesized to coordinate the assembly of infectious virus particles. To determine the role of M2 protein apical targeting in IAV replication, a panel of M2 proteins with basolateral plasma membrane (M2-Baso) or endoplasmic reticulum (M2-ER) targeting sequences was generated. MDCK II cells stably expressing M2-Baso, but not M2-ER, complemented the replication of M2-stop viruses. However, in primary human nasal epithelial cell (hNEC) cultures, viruses encoding M2-Baso and M2-ER replicated to negligible titers compared to those of wild-type virus. M2-Baso replication was negatively correlated with cell polarization. These results demonstrate that M2 apical targeting is essential for IAV replication: targeting M2 to the ER results in a strong, cell type-independent inhibition of virus replication, and targeting M2 to the basolateral membrane has greater effects in hNECs than in MDCK cells.IMPORTANCE Influenza A virus assembly and particle release occur at the apical membrane of polarized epithelial cells. The integral membrane proteins encoded by the virus, HA, NA, and M2, are all targeted to the apical membrane and believed to recruit the other structural proteins to sites of virus assembly. By targeting M2 to the basolateral or endoplasmic reticulum membranes, influenza A virus replication was significantly reduced. Basolateral targeting of M2 reduced the infectious virus titers with minimal effects on virus particle release, while targeting to the endoplasmic reticulum resulted in reduced infectious and total virus particle release. Therefore, altering the expression and the intracellular targeting of M2 has major effects on virus replication.
See Also:
Latest articles in those days:
- [preprint]A systematic review of laboratory investigations into the pathogenesis of avian influenza viruses in wild avifauna of North America 15 hours ago
- [preprint]Seabird and sea duck mortalities were lower during the second breeding season in eastern Canada following the introduction of Highly Pathogenic Avian Influenza A H5Nx viruses 15 hours ago
- [preprint]Novel introductions of human-origin H3N2 Influenza viruses in Swine, Chile 15 hours ago
- Long term evolution of human seasonal influenza virus A(H3N2) is associated with an increase in polymerase complex activity 15 hours ago
- Humoral correlates of protection against influenza A H3N2 virus infection 15 hours ago
[Go Top] [Close Window]