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ORIGINAL ARTICLE

Marked Depletion of Glycosylation Sites in HIV-1 gp120 under Selection Pressure by the Mannose-Specific Plant Lectins of Hippeastrum Hybrid and Galanthus nivalis

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium (J.B., K.V.L., S.H., M.F., E.D.C., D.S.); University Hospitals Leuven, Leuven, Belgium (K.V.L.); Department of Clinical Virology, University of Göteborg, Göteborg, Sweden (A.B.); and Department of Molecular Biotechnology, Ghent University, Ghent, Belgium (E.V.D., W.P.)

Abstract

The plant lectins from Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA) are 50,000-D tetramers showing specificity for -(1,3) and/or -(1,6)-mannose oligomers. They inhibit HIV-1 infection at a 50% effective concentration of 0.2 to 0.3 µg/ml. Escalating HHA or GNA concentrations (up to 500 µg/ml) led to the isolation of three HIV-1(III_B) strains in CEM T cell cultures that were highly resistant to HHA and GNA, several other related mannose-specific plant lectins, and the monoclonal antibody 2G12, modestly resistant to the mannose-specific cyanovirin, which is derived from a blue-green alga, but fully susceptible to other HIV entry inhibitors as well as HIV reverse transcriptase inhibitors. These mutant virus strains were devoid of up to seven or eight of 22 glycosylation sites in the viral envelope glycoprotein gp120 because of mutations at the Asn or Thr/Ser sites of the N-glycosylation motifs. In one of the strains, a novel glycosylation site was created near a deleted glycosylation site. The affected glycosylation sites were predominantly clustered in regions of gp120 that are not involved in the direct interaction with either CD4, CCR5, CXCR4, or gp41. The mutant viruses containing the deleted glycosylation sites were markedly more infectious in CEM T-cell cultures than wild-type virus.

Address correspondence to: Prof. J. Balzarini, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. E-mail: jan.balzarini{at}rega.kuleuven.ac.be

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