Tyrosine 132 Phosphorylation of Influenza A Virus M1 Protein Is Crucial for Virus Replication by Controlling the Nuclear Import of M1

Tyrosine 132 Phosphorylation of Influenza A Virus M1 Protein Is Crucial for Virus Replication by Controlling the Nuclear Import of M1
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甲型流感病毒 M1 蛋白的酪氨酸 132 磷酸化通过控制 M1 的核输入对病毒复制至关重要

DOI:
10.1128/jvi.03024-12
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发表时间:
2013-03
影响因子:
5.4
通讯作者:
Liu, Wenjun
Liu, Wenjun
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Shanshan;Zhao, Zhendong;Bi, Yuhai;Sun, Lei;Liu, Xiaoling;Liu, Wenjun

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摘要 病毒蛋白的磷酸化在甲型流感病毒(IAV)生命周期中发挥着重要作用。通过质谱分析,我们鉴定出酪氨酸132(Y132)是流感病毒A/WSN/1933(H1N1)基质蛋白(M1)的磷酸化位点。该位点的磷酸化通过控制 M1 的核输入对病毒复制过程至关重要。我们进一步证明,磷酸化酪氨酸对于 M1 与核输入因子 importin-α1 的结合至关重要,因为该位点的任何替换都会严重减少这种蛋白质-蛋白质相互作用,并损害 importin-α1 介导的 M1 核输入。此外,导致 M1 入核的酪氨酸磷酸化被 Janus 激酶抑制剂阻断。本研究揭示了这种酪氨酸磷酸化在 M1 的细胞内运输中的关键作用,M1 控制着病毒复制的过程。
ABSTRACT Phosphorylation of viral proteins plays important roles in the influenza A virus (IAV) life cycle. By using mass spectrometry, we identified tyrosine 132 (Y132) as a phosphorylation site of the matrix protein (M1) of the influenza virus A/WSN/1933(H1N1). Phosphorylation at this site is essential to the process of virus replication by controlling the nuclear import of M1. We further demonstrated that the phosphorylated tyrosine is crucial for the binding of M1 to the nuclear import factor importin-α1, since any substitutions at this site severely reduce this protein-protein interaction and damage the importin-α1-mediated nuclear import of M1. Additionally, the tyrosine phosphorylation which leads to the nuclear import of M1 is blocked by a Janus kinase inhibitor. The present study reveals a pivotal role of this tyrosine phosphorylation in the intracellular transportation of M1, which controls the process of viral replication.
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