This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kelkar, S. A. Articles by Leopold, P. L. Search for Related Content PubMed PubMed Citation Articles by Kelkar, S. A. Articles by Leopold, P. L.

 Previous Article  |  Next Article 

Journal of Virology, September 2004, p. 10122-10132, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10122-10132.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Cytoplasmic Dynein Mediates Adenovirus Binding to Microtubules

Department of Genetic Medicine,¹ Graduate Program in Physiology and Biophysics and Systems Biology, Weill Medical College of Cornell University, New York, New York,² Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia³

Received 29 September 2003/ Accepted 27 April 2004

During infection, adenovirus (Ad) capsids undergo microtubule-dependent retrograde transport as part of a program of vectorial transport of the viral genome to the nucleus. The microtubule-associated molecular motor, cytoplasmic dynein, has been implicated in the retrograde movement of Ad. We hypothesized that cytoplasmic dynein constituted the primary mode of association of Ad with microtubules. To evaluate this hypothesis, an Ad-microtubule binding assay was established in which microtubules were polymerized with taxol, combined with Ad in the presence or absence of microtubule-associated proteins (MAPs), and centrifuged through a glycerol cushion. The addition of purified bovine brain MAPs increased the fraction of Ad in the microtubule pellet from 17.3% ± 3.5% to 80.7% ± 3.8% (P < 0.01). In the absence of tubulin polymerization or in the presence of high salt, no Ad was found in the pellet. Ad binding to microtubules was not enhanced by bovine brain MAPs enriched for tau protein or by the addition of bovine serum albumin. Enhanced Ad-microtubule binding was also observed by using a fraction of MAPs purified from lung A549 epithelial cell lysate which contained cytoplasmic dynein. Ad-microtubule interaction was sensitive to the addition of ATP, a hallmark of cytoplasmic dynein-dependent microtubule interactions. Immunodepletion of cytoplasmic dynein from the A549 cell lysate abolished the MAP-enhanced Ad-microtubule binding. The interaction of Ad with both dynein and dynactin complexes was demonstrated by coimmunoprecipitation. Partially uncoated capsids isolated from cells 40 min after infection also exhibited microtubule binding. In summary, the primary mode of Ad attachment to microtubules occurs though cytoplasmic dynein-mediated binding.

This article has been cited by other articles:

• Smith, J. G., Cassany, A., Gerace, L., Ralston, R., Nemerow, G. R. (2008). Neutralizing Antibody Blocks Adenovirus Infection by Arresting Microtubule-Dependent Cytoplasmic Transport. J. Virol. 82: 6492-6500 [Abstract] [Full Text]  
• Wodrich, H., Cassany, A., D'Angelo, M. A., Guan, T., Nemerow, G., Gerace, L. (2006). Adenovirus Core Protein pVII Is Translocated into the Nucleus by Multiple Import Receptor Pathways. J. Virol. 80: 9608-9618 [Abstract] [Full Text]  
• Kelkar, S., De, B. P., Gao, G., Wilson, J. M., Crystal, R. G., Leopold, P. L. (2006). A Common Mechanism for Cytoplasmic Dynein-Dependent Microtubule Binding Shared among Adeno-Associated Virus and Adenovirus Serotypes.. J. Virol. 80: 7781-7785 [Abstract] [Full Text]  
• Warren, J. C., Rutkowski, A., Cassimeris, L. (2006). Infection with Replication-deficient Adenovirus Induces Changes in the Dynamic Instability of Host Cell Microtubules. Mol. Biol. Cell 17: 3557-3568 [Abstract] [Full Text]  
• McConnell, M. J., Danthinne, X., Imperiale, M. J. (2006). Characterization of a permissive epitope insertion site in adenovirus hexon.. J. Virol. 80: 5361-5370 [Abstract] [Full Text]  
• Citterio, C., Jones, H. D., Pacheco-Rodriguez, G., Islam, A., Moss, J., Vaughan, M. (2006). Effect of protein kinase A on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei. Proc. Natl. Acad. Sci. USA 103: 2683-2688 [Abstract] [Full Text]  
• Dinh, A.-T., Theofanous, T., Mitragotri, S. (2005). A Model for Intracellular Trafficking of Adenoviral Vectors. Biophys. J 89: 1574-1588 [Abstract] [Full Text]  
• Salman, H., Abu-Arish, A., Oliel, S., Loyter, A., Klafter, J., Granek, R., Elbaum, M. (2005). Nuclear Localization Signal Peptides Induce Molecular Delivery along Microtubules. Biophys. J 89: 2134-2145 [Abstract] [Full Text]  
• Strunze, S., Trotman, L. C., Boucke, K., Greber, U. F. (2005). Nuclear Targeting of Adenovirus Type 2 Requires CRM1-mediated Nuclear Export. Mol. Biol. Cell 16: 2999-3009 [Abstract] [Full Text]  
• Kosturko, L. D., Maggipinto, M. J., D'Sa, C., Carson, J. H., Barbarese, E. (2005). The Microtubule-associated Protein Tumor Overexpressed Gene Binds to the RNA Trafficking Protein Heterogeneous Nuclear Ribonucleoprotein A2. Mol. Biol. Cell 16: 1938-1947 [Abstract] [Full Text]