Influenza A Virus M2 Protein Apical Targeting Is Required for Efficient Virus Replication

Journal of Virology
Nicholas WohlgemuthAndrew Pekosz

Abstract

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 viru...Continue Reading

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Citations

Oct 21, 2019·Journal of Biomedical Science·Daria MezhenskayaLarisa Rudenko
Nov 23, 2018·Journal of Virology·Nicolas CapelliSabine Chapuy-Regaud
Feb 10, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hang YinSong Wang

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