RT Journal Article
SR Electronic
T1 Marked Depletion of Glycosylation Sites in HIV-1 gp120 under Selection Pressure by the Mannose-Specific Plant Lectins of <em>Hippeastrum</em> Hybrid and <em>Galanthus nivalis</em>
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1556
OP 1565
DO 10.1124/mol.104.005082
VO 67
IS 5
A1 Balzarini, Jan
A1 Van Laethem, Kristel
A1 Hatse, Sigrid
A1 Froeyen, Matheus
A1 Van Damme, Els
A1 Bolmstedt, Anders
A1 Peumans, Willy
A1 De Clercq, Erik
A1 Schols, Dominique
YR 2005
UL http://molpharm.aspetjournals.org/content/67/5/1556.abstract
AB The plant lectins from Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA) are 50,000-D tetramers showing specificity for α-(1,3) and/or α-(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(IIIB) 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.