Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Exploratory Research for Advanced Technology Infection-Induced Host Responses Project, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Nat Microbiol. 2016 May 16;1(8):16062. doi: 10.1038/nmicrobiol.2016.62.
The nucleus is highly compartmentalized yet dynamic. Subnuclear functions are regulated by controlling the subnuclear localization of the nuclear proteins. Influenza viral ribonucleoprotein (vRNP) is replicated in the nucleus and then exported to the cytoplasm. However, the precise subnuclear localization and transport of vRNPs remain unclear. Here, we show that CLUH, a host protein whose cellular function is not well established, plays a key role in the subnuclear transport of vRNP. Viral PB2 and M1 induced CLUH translocation to the nucleoplasm and SC35-positive speckles, respectively, even though CLUH is usually cytoplasmic. CLUH depletion inhibited the translocation of M1 to SC35-positive speckles, but did not interfere with PB2 localization to the nucleoplasm and disrupted the subnuclear transport of vRNP, abolishing vRNP nuclear export without affecting viral RNA or protein expression. Our findings suggest that CLUH plays a role in the subnuclear transport of progeny vRNP.
核是高度分隔的，但又是动态的。亚核功能的调节是通过控制核蛋白的亚核定位来实现的。流感病毒核糖核蛋白（vRNP）在核内复制，然后输出到细胞质。然而，vRNPs 的精确亚核定位和运输仍然不清楚。在这里，我们表明，CLUH，一种其细胞功能尚未明确的宿主蛋白，在 vRNP 的亚核运输中起着关键作用。病毒 PB2 和 M1 分别诱导 CLUH 向核质和 SC35 阳性斑点的易位，尽管 CLUH 通常在细胞质中。CLUH 的耗竭抑制了 M1 向 SC35 阳性斑点的易位，但不干扰 PB2 向核质的定位，并破坏 vRNP 的亚核运输，从而阻止 vRNP 的核输出，而不影响病毒 RNA 或蛋白的表达。我们的研究结果表明，CLUH 在子代 vRNP 的亚核运输中发挥作用。
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