Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins
Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins
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DOI：
10.1128/jvi.70.12.8391-8401.1996
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发表时间：
1996-12-01
影响因子：
5.4
通讯作者：
Helenius, A
中科院分区：
文献类型：
--
作者：
Bui, M;Whittaker, G;Helenius, A
流感病毒通过受体介导的内吞作用进入宿主细胞，然后在内体中进行酸激活的膜融合。病毒核糖核蛋白颗粒 (vRNP) 被递送到细胞质中，然后与基质蛋白 M1 解离，并相互解离，之后它们通过核孔单独输入细胞核。一段时间以来，人们认为核内体的低 pH 可能以某种方式触发核运输所需的衣壳解体事件。该报告提供了直接证据，表明 M1 与 vRNP 的结合对受感染细胞内的弱酸性 pH 敏感。在培养细胞中表达的重组M1被发现与vRNP结合并抑制其核输入，胞质区室的短暂酸化消除了干扰活性并允许传入的vRNP进入细胞核，受感染细胞的胞质溶胶中新组装的子代M1-vRNP复合物也通过短暂酸化而解离，因此发现酸性pH作为一个开关，使M1能够在脱壳中提前发挥其多种功能，核运输和 vRNP 组装。
Influenza virus enters its host cell by receptor-mediated endocytosis followed by acid-activated membrane fusion in endosomes. The viral ribonucleoprotein particles (vRNPs) delivered into the cytosol then dissociate from the matrix protein, M1, and from each other, after which they are individually imported into the nucleus via the nuclear pores, For some time, it has been believed that the low pH in endosomes may, in some way, trigger the capsid disassembly events necessary for nuclear transport, This report provides direct evidence that the association of M1 with vRNPs is sensitive to mildly acidic pH within the infected cell. Recombinant M1, expressed in cultured cells, was found to associate with vRNPs and inhibit their nuclear import, Brief acidification of the cytosolic compartment eliminated the interfering activity and allowed the incoming vRNPs to enter the nucleus, Newly assembled progeny M1-vRNP complexes in the cytosol of infected cells were also dissociated by brief acidification, Acidic pH was thus found to serve as a switch that allowed M1 to early out its multiple functions in the uncoating, nuclear transport, and assembly of vRNPs.