![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on June 1, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 11, 2005
Revised on March 24, 2005
Accepted on March 29, 2005
University of Zürich, Institute of Zoology, CH-8057 Zürich, Switzerland
Monitoring Editor: Karsten Weis
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.
Present address: Molecular and Developmental Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Address correspondence to:
Urs F. Greber (ufgreber{at}zool.unizh.ch)
This article has been cited by other articles:
|
|
 |
|
  J. G. Smith, A. Cassany, L. Gerace, R. Ralston, and G. R. Nemerow Neutralizing Antibody Blocks Adenovirus Infection by Arresting Microtubule-Dependent Cytoplasmic Transport J. Virol., July 1, 2008; 82(13): 6492 - 6500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Yea, J. Dembowy, L. Pacione, and M. Brown Microtubule-Mediated and Microtubule-Independent Transport of Adenovirus Type 5 in HEK293 Cells J. Virol., July 1, 2007; 81(13): 6899 - 6908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Shyu, T.-L. Lee, S.-C. Wen, H. Chen, W.-Y. Hsiao, X. Chen, J. Hwang, and C.-K. J. Shen Subcellular Transport of EKLF and Switch-On of Murine Adult {beta}maj Globin Gene Transcription Mol. Cell. Biol., March 15, 2007; 27(6): 2309 - 2323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Leopold, R. L. Wendland, T. Vincent, and R. G. Crystal Neutralized Adenovirus-Immune Complexes Can Mediate Effective Gene Transfer via an Fc Receptor-Dependent Infection Pathway. J. Virol., October 1, 2006; 80(20): 10237 - 10247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-T. Dinh, T. Theofanous, and S. Mitragotri A Model for Intracellular Trafficking of Adenoviral Vectors Biophys. J., September 1, 2005; 89(3): 1574 - 1588. [Abstract] [Full Text] [PDF]
|
|
