This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Fournillier, A.
Right arrow Articles by Inchauspé, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fournillier, A.
Right arrow Articles by Inchauspé, G.

 Previous Article  |  Next Article 

Journal of Virology, December 2001, p. 12088-12097, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12088-12097.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Induction of Hepatitis C Virus E1 Envelope Protein-Specific Immune Response Can Be Enhanced by Mutation of N-Glycosylation Sites

A. Fournillier,1,2 C. Wychowski,3 D. Boucreux,2 T. F. Baumert,4 J.-C. Meunier,3 D. Jacobs,5 S. Muguet,2 E. Depla,5 and G. Inchauspé2,*

Unité Mixte CNRS/BioMérieux, 69364 Lyon Cédex 07,1 INSERM U271, Virus des Hépatites, Rétrovirus Humains et Pathologies Associées, 69424 Lyon Cédex 03,2 and CNRS, FRE 2369, IBL/Institut Pasteur de Lille, 59021 Lille Cedex,3 France; Department of Medicine, University of Freiburg, Freiburg, Germany4; and Hepatitis Program, Innogenetics, B-9052 Ghent, Belgium5

Received 11 June 2001/Accepted 6 September 2001

Deglycosylation of viral glycoproteins has been shown to influence the number of available epitopes and to modulate immune recognition of antigens. We investigated the role played by N-glycans in the immunogenicity of hepatitis C virus (HCV) E1 envelope glycoprotein, a naturally poor immunogen. Eight plasmids were engineered, encoding E1 protein mutants in which the four N-linked glycosylation sites of the protein were mutated separately or in combination. In vitro expression studies showed an influence of N-linked glycosylation on expression efficiency, instability, and/or secretion of the mutated proteins. Immunogenicity of the E1 mutants was studied in BALB/c mice following intramuscular and intraepidermal injection of the plasmids. Whereas some mutations had no or only minor effects on the antibody titers induced, mutation of the fourth glycosylation site (N4) significantly enhanced the anti-E1 humoral response in terms of both seroconversion rates and antibody titers. Moreover, antibody induced by the N4 mutant was able to recognize HCV-like particles with higher titers than those induced by the wild-type construct. Epitope mapping indicated that the E1 mutant antigens induced antibody directed at two major domains: one, located at amino acids (aa) 313 to 332, which is known to be reactive with sera from HCV patients, and a second one, located in the N-terminal domain of E1 (aa 192 to 226). Analysis of the induced immune cellular response confirmed the induction of gamma interferon-producing cells by all mutants, albeit to different levels. These results show that N-linked glycosylation can limit the antibody response to the HCV E1 protein and reveal a potential vaccine candidate with enhanced immunogenicity.

* Corresponding author. Mailing address: Unité Mixte CNRS/Bio-Mérieux, 69364 Lyon Cédex 07, France. Phone: 33.4.72.72.85.90. Fax: 33.4.72.72.85.33. E-mail: genevieve.inchauspe{at}ens-lyon.fr.

Journal of Virology, December 2001, p. 12088-12097, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12088-12097.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Humphreys, I., Fleming, V., Fabris, P., Parker, J., Schulenberg, B., Brown, A., Demetriou, C., Gaudieri, S., Pfafferott, K., Lucas, M., Collier, J., Huang, K.-H. G., Pybus, O. G., Klenerman, P., Barnes, E. (2009). Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection. J. Virol. 83: 11456-11466 [Abstract] [Full Text]  
  • Sugimoto, C., Nakayama, E. E., Shioda, T., Villinger, F., Ansari, A. A., Yamamoto, N., Suzuki, Y., Nagai, Y., Mori, K. (2008). Impact of glycosylation on antigenicity of simian immunodeficiency virus SIV239: induction of rapid V1/V2-specific non-neutralizing antibody and delayed neutralizing antibody following infection with an attenuated deglycosylated mutant. J. Gen. Virol. 89: 554-566 [Abstract] [Full Text]  
  • Helle, F., Goffard, A., Morel, V., Duverlie, G., McKeating, J., Keck, Z.-Y., Foung, S., Penin, F., Dubuisson, J., Voisset, C. (2007). The Neutralizing Activity of Anti-Hepatitis C Virus Antibodies Is Modulated by Specific Glycans on the E2 Envelope Protein. J. Virol. 81: 8101-8111 [Abstract] [Full Text]  
  • Brown, R. J. P., Tarr, A. W., McClure, C. P., Juttla, V. S., Tagiuri, N., Irving, W. L., Ball, J. K. (2007). Cross-genotype characterization of genetic diversity and molecular adaptation in hepatitis C virus envelope glycoprotein genes. J. Gen. Virol. 88: 458-469 [Abstract] [Full Text]  
  • Brown, R. J. P., Juttla, V. S., Tarr, A. W., Finnis, R., Irving, W. L., Hemsley, S., Flower, D. R., Borrow, P., Ball, J. K. (2005). Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection. J. Gen. Virol. 86: 1931-1942 [Abstract] [Full Text]  
  • Genovese, D., Dettori, S., Argentini, C., Villano, U., Chionne, P., Angelico, M., Rapicetta, M. (2005). Molecular Epidemiology of Hepatitis C Virus Genotype 4 Isolates in Egypt and Analysis of the Variability of Envelope Proteins E1 and E2 in Patients with Chronic Hepatitis. J. Clin. Microbiol. 43: 1902-1909 [Abstract] [Full Text]  
  • Zhang, M., Gaschen, B., Blay, W., Foley, B., Haigwood, N., Kuiken, C., Korber, B. (2004). Tracking global patterns of N-linked glycosylation site variation in highly variable viral glycoproteins: HIV, SIV, and HCV envelopes and influenza hemagglutinin. Glycobiology 14: 1229-1246 [Abstract] [Full Text]  
  • Karayiannis, P., Main, J., Thomas, H. C. (2004). Hepatitis vaccines. Br Med Bull 70: 29-49 [Full Text]  
  • Sheridan, I., Pybus, O. G., Holmes, E. C., Klenerman, P. (2004). High-Resolution Phylogenetic Analysis of Hepatitis C Virus Adaptation and Its Relationship to Disease Progression. J. Virol. 78: 3447-3454 [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»