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 Balzarini, J.
Right arrow Articles by Schols, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Balzarini, J.
Right arrow Articles by Schols, D.

 Previous Article  |  Next Article 

Journal of Virology, September 2006, p. 8411-8421, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00369-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mutational Pathways, Resistance Profile, and Side Effects of Cyanovirin Relative to Human Immunodeficiency Virus Type 1 Strains with N-Glycan Deletions in Their gp120 Envelopes

Jan Balzarini,1* Kristel Van Laethem,1 Willy J. Peumans,2 Els J. M. Van Damme,2 Anders Bolmstedt,3 Federico Gago,4 and Dominique Schols1

Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium,1 Ghent University, Ghent, Belgium,2 Department of Clinical Virology, University of Göteborg, Göteborg, Sweden,3 Department of Pharmacology, University of Alcalá, Madrid, Spain4

Received 22 February 2006/ Accepted 5 June 2006

Limited data are available on the genotypic and phenotypic resistance profile of the {alpha}-(1-2)mannose oligomer-specific prokaryotic lectin cyanovirin (CV-N). Therefore, a more systematic investigation was carried out to obtain a better view of the interaction between CV-N and human immunodeficiency virus type 1 (HIV-1) gp120. When HIV-1-infected CEM cell cultures were exposed to CV-N in a dose-escalating manner, a total of eight different amino acid mutations exclusively located at N-glycosylation sites in the envelope surface gp120 were observed. Six of the eight mutations resulted in the deletion of high-mannose type N-glycans (i.e., at amino acid positions 230, 332, 339, 386, 392, and 448). Two mutations (i.e., at position 136 and 160) deleted a complex type N-glycan in the variable V1/V2 domain of gp120. The level of phenotypic resistance of the mutated virus strains against CV-N generally correlated with the number of glycan deletions in gp120, although deletion of the glycans at N-230, N-392, and N-448 generally afforded a more pronounced CV-N resistance than other N-glycan deletions. However, the extent of the decrease of antiviral activity of CV-N against the mutated virus strains was markedly less pronounced than observed for {alpha}(1-3)- and {alpha}(1-6)-mannose-specific plant lectins Hippeastrum hybrid agglutinin (HHA) and Galanthus nivalis agglutinin (GNA), which points to the existence of a higher genetic barrier for CV-N. This is in agreement with a more consistent suppression of a wider variety of HIV-1 clades by CV-N than by HHA and GNA. Whereas the antiviral and in vitro antiproliferative activity of CV-N can be efficiently reversed by mannan, the pronounced mitogenic activity of CV-N on peripheral blood mononuclear cells was unaffected by mannan, indicating that some of the observed side effects of CV-N are unrelated to its carbohydrate specificity/activity.

* Corresponding author. Mailing address: Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32 16 337352. Fax: 32 16 337340. E-mail: jan.balzarini{at}rega.kuleuven.be.

Journal of Virology, September 2006, p. 8411-8421, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00369-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vermeire, K., Van Laethem, K., Janssens, W., Bell, T. W., Schols, D. (2009). Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol. 83: 9577-9583 [Abstract] [Full Text]  
  • Tanaka, H., Chiba, H., Inokoshi, J., Kuno, A., Sugai, T., Takahashi, A., Ito, Y., Tsunoda, M., Suzuki, K., Takenaka, A., Sekiguchi, T., Umeyama, H., Hirabayashi, J., Omura, S. (2009). Mechanism by which the lectin actinohivin blocks HIV infection of target cells. Proc. Natl. Acad. Sci. USA 106: 15633-15638 [Abstract] [Full Text]  
  • Benoist, H., Culerrier, R., Poiroux, G., Segui, B., Jauneau, A., Van Damme, E. J. M., Peumans, W. J., Barre, A., Rouge, P. (2009). Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death. J. Leukoc. Biol. 86: 103-114 [Abstract] [Full Text]  
  • Buffa, V., Stieh, D., Mamhood, N., Hu, Q., Fletcher, P., Shattock, R. J. (2009). Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models. J. Gen. Virol. 90: 234-243 [Abstract] [Full Text]  
  • van der Meer, F. J. U. M., de Haan, C. A. M., Schuurman, N. M. P., Haijema, B. J., Verheije, M. H., Bosch, B. J., Balzarini, J., Egberink, H. F. (2007). The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins. J Antimicrob Chemother 60: 741-749 [Abstract] [Full Text]  
  • Balzarini, J., Van Laethem, K., Daelemans, D., Hatse, S., Bugatti, A., Rusnati, M., Igarashi, Y., Oki, T., Schols, D. (2007). Pradimicin A, a Carbohydrate-Binding Nonpeptidic Lead Compound for Treatment of Infections with Viruses with Highly Glycosylated Envelopes, Such as Human Immunodeficiency Virus. J. Virol. 81: 362-373 [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»