This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wölk, B.
Right arrow Articles by Rice, C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wölk, B.
Right arrow Articles by Rice, C. M.

 Previous Article  |  Next Article 

Journal of Virology, November 2008, p. 10519-10531, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00640-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Dynamic View of Hepatitis C Virus Replication Complexes{triangledown} ,{ddagger}

Benno Wölk,1,2,3,{dagger} Benjamin Büchele,2,{dagger},§ Darius Moradpour,2,4* and Charles M. Rice1*

Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, New York, New York 10065,1 Department of Medicine II, University of Freiburg, D-79106 Freiburg, Germany,2 Department of Virology, Hannover Medical School, D-30625 Hannover, Germany,3 Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, CH-1011 Lausanne, Switzerland4

Received 21 March 2008/ Accepted 12 August 2008

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex (RC). Specific membrane alterations, designated membranous webs, represent predominant sites of HCV RNA replication. The principles governing HCV RC and membranous web formation are poorly understood. Here, we used replicons harboring a green fluorescent protein (GFP) insertion in nonstructural protein 5A (NS5A) to study HCV RCs in live cells. Two distinct patterns of NS5A-GFP were observed. (i) Large structures, representing membranous webs, showed restricted motility, were stable over many hours, were partitioned among daughter cells during cell division, and displayed a static internal architecture without detectable exchange of NS5A-GFP. (ii) In contrast, small structures, presumably representing small RCs, showed fast, saltatory movements over long distances. Both populations were associated with endoplasmic reticulum (ER) tubules, but only small RCs showed ER-independent, microtubule (MT)-dependent transport. We suggest that this MT-dependent transport sustains two distinct RC populations, which are both required during the HCV life cycle.

* Corresponding authors. Mailing address for D. Moradpour: Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. Phone: 41 21 314 47 23. Fax: 41 21 314 47 18. E-mail: Darius.Moradpour{at}chuv.ch. Mailing address for C. M. Rice: Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Avenue, Box 64, New York, NY 10065. Phone: (212) 327-7046. Fax: (212) 327-7048. E-mail: ricec{at}rockefeller.edu

{triangledown} Published ahead of print on 20 August 2008.

{ddagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} B.W. and B.B. contributed equally to this study.

§ Present address: Neurologische Klinik des Städtischen Klinikums Karlsruhe, 76133 Karlsruhe, Germany.

Journal of Virology, November 2008, p. 10519-10531, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.00640-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cotton, S., Grangeon, R., Thivierge, K., Mathieu, I., Ide, C., Wei, T., Wang, A., Laliberte, J.-F. (2009). Turnip Mosaic Virus RNA Replication Complex Vesicles Are Mobile, Align with Microfilaments, and Are Each Derived from a Single Viral Genome. J. Virol. 83: 10460-10471 [Abstract] [Full Text]  
  • Taguwa, S., Kambara, H., Omori, H., Tani, H., Abe, T., Mori, Y., Suzuki, T., Yoshimori, T., Moriishi, K., Matsuura, Y. (2009). Cochaperone Activity of Human Butyrate-Induced Transcript 1 Facilitates Hepatitis C Virus Replication through an Hsp90-Dependent Pathway. J. Virol. 83: 10427-10436 [Abstract] [Full Text]  
  • Roohvand, F., Maillard, P., Lavergne, J.-P., Boulant, S., Walic, M., Andreo, U., Goueslain, L., Helle, F., Mallet, A., McLauchlan, J., Budkowska, A. (2009). Initiation of Hepatitis C Virus Infection Requires the Dynamic Microtubule Network: ROLE OF THE VIRAL NUCLEOCAPSID PROTEIN. J. Biol. Chem. 284: 13778-13791 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»