Nuclear targeting of adenovirus type 2 requires CRM1-mediated nuclear export

Strunze, S., Trotman, L. C., Boucke, K., Greber, U. F. (2005) Nuclear targeting of adenovirus type 2 requires CRM1-mediated nuclear export. Molecular Biology of the Cell, 16 (6). pp. 2999-3009. ISSN 10591524 (ISSN)

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DOI: 10.1091/mbc.E05-02-0121


Incoming adenovirus type 2 (Ad2) and Ad5 shuttle bidirectionally along microtubules, biased to the microtubule-organizing center by the dynein/dynactin motor complex. It is unknown how the particles reach the nuclear pore complex, where capsids disassemble and viral DNA enters the nucleus. Here, we identified a novel link between nuclear export and microtubule-mediated transport. Two distinct inhibitors of the nuclear export factor CRM1, leptomycin B (LMB) and ratjadone A (RJA) or CRM1-siRNAs blocked adenovirus infection, arrested cytoplasmic transport of viral particles at the microtubule-organizing center or in the cytoplasm and prevented capsid disassembly and nuclear import of the viral genome. In mitotic cells where CRM1 is in the cytoplasm, adenovirus particles were not associated with microtubules but upon LMB treatment, they enriched at the spindle poles implying that CRM1 inhibited microtubule association of adenovirus. We propose that CRM1, a nuclear factor exported by CRM1 or a protein complex containing CRM1 is part of a sensor mechanism triggering the unloading of the incoming adenovirus particles from microtubules proximal to the nucleus of interphase cells. © 2005 by The American Society for Cell Biology.

Item Type: Paper
Uncontrolled Keywords: exportin 1 leptomycin B ratjadone a small interfering RNA unclassified drug Adenovirus 2 Adenovirus 5 animal cell article cell synchronization cytoplasm HeLa cell human human cell interphase microtubule nonhuman nuclear import nuclear pore complex priority journal virus capsid virus infection virus particle Western blotting Active Transport, Cell Nucleus Adenoviridae Animals Blotting, Western Cell Line Cell Line, Tumor Cell Nucleus Cercopithecus aethiops Endothelium, Vascular Fatty Acids, Unsaturated Green Fluorescent Proteins Hela Cells Humans Karyopherins Microscopy, Confocal Microtubule-Organizing Center Mitosis Mitotic Spindle Apparatus Pyrones Receptors, Cytoplasmic and Nuclear RNA, Small Interfering Transferrin Umbilical Veins Human adenovirus type 2 Miridae
Subjects: organism description > virus > viral transfection
CSHL Authors:
Communities: CSHL labs > Trotman lab
Depositing User: Brian Soldo
Date: 2005
Date Deposited: 23 Mar 2012 16:08
Last Modified: 08 May 2013 16:42
PMCID: PMC1142442
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