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 Zhong, J.
Right arrow Articles by Chisari, F. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhong, J.
Right arrow Articles by Chisari, F. V.

 Previous Article  |  Next Article 

Journal of Virology, November 2006, p. 11082-11093, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01307-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Persistent Hepatitis C Virus Infection In Vitro: Coevolution of Virus and Host{triangledown},{dagger}

Jin Zhong,1 Pablo Gastaminza,1 Josan Chung,1 Zania Stamataki,1 Masanori Isogawa,2 Guofeng Cheng,2 Jane A. McKeating,2 and Francis V. Chisari1*

Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037,1 Division of Immunity and Infection, Institute of Biomedical Research, Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom2

Received 21 June 2006/ Accepted 29 August 2006

The virological and cellular consequences of persistent hepatitis C virus (HCV) infection have been elusive due to the absence of the requisite experimental systems. Here, we report the establishment and the characteristics of persistent in vitro infection of human hepatoma-derived cells by a recently described HCV genotype 2a infectious molecular clone. Persistent in vitro infection was characterized by the selection of viral variants that displayed accelerated expansion kinetics, higher peak titers, and increased buoyant densities. Sequencing analysis revealed the selection of a single adaptive mutation in the HCV E2 envelope protein that was largely responsible for the variant phenotype. In parallel, as the virus became more aggressive, cells that were resistant to infection emerged, displaying escape mechanisms operative at the level of viral entry, HCV RNA replication, or both. Collectively, these results reveal the existence of coevolutionary events during persistent HCV infection that favor survival of both virus and host.

* Corresponding author. Mailing address: Department of Molecular and Experimental Medicine, SBR-10, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037. Phone: (858) 784-8228. Fax: (858) 784-2160. E-mail: fchisari{at}scripps.edu.

{triangledown} Published ahead of print on 6 September 2006.

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

Journal of Virology, November 2006, p. 11082-11093, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01307-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bungyoku, Y., Shoji, I., Makine, T., Adachi, T., Hayashida, K., Nagano-Fujii, M., Ide, Y.-H., Deng, L., Hotta, H. (2009). Efficient production of infectious hepatitis C virus with adaptive mutations in cultured hepatoma cells. J. Gen. Virol. 90: 1681-1691 [Abstract] [Full Text]  
  • Grove, J., Nielsen, S., Zhong, J., Bassendine, M. F., Drummer, H. E., Balfe, P., McKeating, J. A. (2008). Identification of a Residue in Hepatitis C Virus E2 Glycoprotein That Determines Scavenger Receptor BI and CD81 Receptor Dependency and Sensitivity to Neutralizing Antibodies. J. Virol. 82: 12020-12029 [Abstract] [Full Text]  
  • Ma, Y., Yates, J., Liang, Y., Lemon, S. M., Yi, M. (2008). NS3 Helicase Domains Involved in Infectious Intracellular Hepatitis C Virus Particle Assembly. J. Virol. 82: 7624-7639 [Abstract] [Full Text]  
  • Woodhouse, S. D., Smith, C., Michelet, M., Branza-Nichita, N., Hussey, M., Dwek, R. A., Zitzmann, N. (2008). Iminosugars in Combination with Interferon and Ribavirin Permanently Eradicate Noncytopathic Bovine Viral Diarrhea Virus from Persistently Infected Cells. Antimicrob. Agents Chemother. 52: 1820-1828 [Abstract] [Full Text]  
  • Russell, R. S., Meunier, J.-C., Takikawa, S., Faulk, K., Engle, R. E., Bukh, J., Purcell, R. H., Emerson, S. U. (2008). Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus. Proc. Natl. Acad. Sci. USA 105: 4370-4375 [Abstract] [Full Text]  
  • Gastaminza, P., Cheng, G., Wieland, S., Zhong, J., Liao, W., Chisari, F. V. (2008). Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion. J. Virol. 82: 2120-2129 [Abstract] [Full Text]  
  • Scheel, T. K. H., Gottwein, J. M., Jensen, T. B., Prentoe, J. C., Hoegh, A. M., Alter, H. J., Eugen-Olsen, J., Bukh, J. (2008). Development of JFH1-based cell culture systems for hepatitis C virus genotype 4a and evidence for cross-genotype neutralization. Proc. Natl. Acad. Sci. USA 105: 997-1002 [Abstract] [Full Text]  
  • Herrera, M., Grande-Perez, A., Perales, C., Domingo, E. (2008). Persistence of foot-and-mouth disease virus in cell culture revisited: implications for contingency in evolution. J. Gen. Virol. 89: 232-244 [Abstract] [Full Text]  
  • Shavinskaya, A., Boulant, S., Penin, F., McLauchlan, J., Bartenschlager, R. (2007). The Lipid Droplet Binding Domain of Hepatitis C Virus Core Protein Is a Major Determinant for Efficient Virus Assembly. J. Biol. Chem. 282: 37158-37169 [Abstract] [Full Text]  
  • Kaul, A., Woerz, I., Meuleman, P., Leroux-Roels, G., Bartenschlager, R. (2007). Cell Culture Adaptation of Hepatitis C Virus and In Vivo Viability of an Adapted Variant. J. Virol. 81: 13168-13179 [Abstract] [Full Text]  
  • Delgrange, D., Pillez, A., Castelain, S., Cocquerel, L., Rouille, Y., Dubuisson, J., Wakita, T., Duverlie, G., Wychowski, C. (2007). Robust production of infectious viral particles in Huh-7 cells by introducing mutations in hepatitis C virus structural proteins. J. Gen. Virol. 88: 2495-2503 [Abstract] [Full Text]  
  • Tellinghuisen, T. L., Evans, M. J., von Hahn, T., You, S., Rice, C. M. (2007). Studying Hepatitis C Virus: Making the Best of a Bad Virus. J. Virol. 81: 8853-8867 [Full Text]  
  • Tani, H., Komoda, Y., Matsuo, E., Suzuki, K., Hamamoto, I., Yamashita, T., Moriishi, K., Fujiyama, K., Kanto, T., Hayashi, N., Owsianka, A., Patel, A. H., Whitt, M. A., Matsuura, Y. (2007). Replication-Competent Recombinant Vesicular Stomatitis Virus Encoding Hepatitis C Virus Envelope Proteins. J. Virol. 81: 8601-8612 [Abstract] [Full Text]  
  • Akazawa, D., Date, T., Morikawa, K., Murayama, A., Miyamoto, M., Kaga, M., Barth, H., Baumert, T. F., Dubuisson, J., Wakita, T. (2007). CD81 Expression Is Important for the Permissiveness of Huh7 Cell Clones for Heterogeneous Hepatitis C Virus Infection. J. Virol. 81: 5036-5045 [Abstract] [Full Text]  
  • Schaller, T., Appel, N., Koutsoudakis, G., Kallis, S., Lohmann, V., Pietschmann, T., Bartenschlager, R. (2007). Analysis of Hepatitis C Virus Superinfection Exclusion by Using Novel Fluorochrome Gene-Tagged Viral Genomes. J. Virol. 81: 4591-4603 [Abstract] [Full Text]  
  • Tscherne, D. M., Evans, M. J., von Hahn, T., Jones, C. T., Stamataki, Z., McKeating, J. A., Lindenbach, B. D., Rice, C. M. (2007). Superinfection Exclusion in Cells Infected with Hepatitis C Virus. J. Virol. 81: 3693-3703 [Abstract] [Full Text]  
  • Grove, J., Huby, T., Stamataki, Z., Vanwolleghem, T., Meuleman, P., Farquhar, M., Schwarz, A., Moreau, M., Owen, J. S., Leroux-Roels, G., Balfe, P., McKeating, J. A. (2007). Scavenger Receptor BI and BII Expression Levels Modulate Hepatitis C Virus Infectivity. J. Virol. 81: 3162-3169 [Abstract] [Full Text]  
  • Travers, S. A. A., Fares, M. A. (2007). Functional Coevolutionary Networks of the Hsp70-Hop-Hsp90 System Revealed through Computational Analyses. Mol Biol Evol 24: 1032-1044 [Abstract] [Full Text]  
  • Ciupe, S. M., Ribeiro, R. M., Nelson, P. W., Dusheiko, G., Perelson, A. S. (2007). The role of cells refractory to productive infection in acute hepatitis B viral dynamics. Proc. Natl. Acad. Sci. USA 104: 5050-5055 [Abstract] [Full Text]  
  • Gastaminza, P., Kapadia, S. B., Chisari, F. V. (2006). Differential Biophysical Properties of Infectious Intracellular and Secreted Hepatitis C Virus Particles. J. Virol. 80: 11074-11081 [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»