Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Cα-mediated activation of ERK signaling
Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export of the viral genome via protein kinase Cα-mediated activation of ERK signaling
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DOI：
10.1074/jbc.m510233200
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发表时间：
2006-06-16
影响因子：
4.8
通讯作者：
Pleschka, Stephan
中科院分区：
文献类型：
--
作者：
Marjuki, Henju;Alam, Mohammad I.;Pleschka, Stephan
流感病毒基因组的复制和转录仅发生在受感染细胞的细胞核内。病毒RNA基因组、聚合酶亚基和核蛋白形成核糖核蛋白（RNP）复合物。在感染周期的后期，RNP必须从细胞核输出，以在细胞膜上被转移到出芽的后代病毒体中。该过程需要病毒激活细胞Raf/MEK/ERK（促分裂原活化蛋白激酶（MAPK））信号级联，其在感染周期后期被激活。因此，阻断级联导致RNP输出延迟和子代病毒滴度降低。在本研究中，我们分析了病毒血凝素糖蛋白的细胞膜协会的重要性，病毒MAPK激活。我们表明，血凝素膜积累和它的紧密联系与脂筏域触发激活MAPK级联通过蛋白激酶C α激活，并诱导RNP出口。这可能代表了一种自动调节机制，其将RNP输出的时间协调到所有病毒组分准备好进行病毒出芽的时间点。
Replication and transcription of the influenza virus genome takes place exclusively within the nucleus of the infected cells. The viral RNA genome, polymerase subunits, and nucleoprotein form ribonucleoprotein (RNP) complexes. Late in the infectious cycle RNPs have to be exported from the nucleus to be enwrapped into budding progeny virions at the cell membrane. This process requires viral activation of the cellular Raf/MEK/ERK (mitogen-activated protein kinase ( MAPK)) signaling cascade that is activated late in the infection cycle. Accordingly, block of the cascade results in retardation of RNP export and reduced titers of progeny virus. In the present study we have analyzed the importance of cell-membrane association of the viral hemagglutinin glycoprotein for viral MAPK activation. We show that hemagglutinin membrane accumulation and its tight association with lipid-raft domains trigger activation of the MAPK cascade via protein kinase C alpha activation and induces RNP export. This may represent an auto-regulative mechanism that coordinates timing of RNP export to a point when all viral components are ready for virus budding.