dc.contributor.author | Balzarini, Jan | |
dc.contributor.author | Laethem, Kristel van | |
dc.contributor.author | Peumans, Willy J. | |
dc.contributor.author | Damme, Els J. M. van | |
dc.contributor.author | Bolmstedt, Anders | |
dc.contributor.author | Gago Badenas, Federico | |
dc.contributor.author | Schols, Dominique | |
dc.date.accessioned | 2009-11-25T13:09:25Z | |
dc.date.available | 2009-11-25T13:09:25Z | |
dc.date.issued | 2006 | |
dc.identifier.bibliographicCitation | JOURNAL OF VIROLOGY, Sept. 2006, p. 8411-8421 | en_US |
dc.identifier.uri | http://hdl.handle.net/10017/5045 | |
dc.description.abstract | 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. | en_US |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en_US |
dc.publisher | American Society for Microbiology | en_US |
dc.title | 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 | en_US |
dc.type | info:eu-repo/semantics/article | en |
dc.subject.eciencia | Ciencia | es_ES |
dc.subject.eciencia | Farmacología | es_ES |
dc.subject.eciencia | Science | en |
dc.subject.eciencia | Pharmacology | en |
dc.contributor.affiliation | Universidad de Alcalá. Departamento de Farmacología | |
dc.relation.publisherversion | http://dx.doi.org/10.1128/JVI.00369-06 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | en_US |
dc.identifier.doi | 10.1128/JVI.00369-06 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | en |