科學家發現甲型流感病毒M2蛋白頂端靶點在病毒複製中具有重要作用

甲型流感病毒（IAV）M2蛋白是一種多功能的蛋白，在病毒的侵入、組裝及釋放方面起到重要的作用。近日，來自美國的科學家發現，M2蛋白頂端在IAV的有效複製過程中起到了重要的作用。該研究成果目前已發表至《Journal of Virology》雜誌，題為「Influenza A Virus M2 Protein Apical Targeting Is Required for Efficient Virus Replication」。

為了研究M2蛋白頂端靶點在IAV複製過程中的作用，研究人員將IAV的M2蛋白頂端氨基酸序列分別進行了突變：1）引進C-terminal KKXX motif內質網（ER）滯留信號；2）添加C-terminal AAASLLAP基地外側質膜（Baso）靶向序列。

研究成果發現，M2蛋白改造後的IAV的病毒複製能力相對於野毒株顯著下降，證實M2蛋白頂端在IAV複製過程中起到重要作用，且其M2蛋白頂端靶向ER的作用最強。

原文摘要

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.

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