Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis.
The plant lectins from Hippeastrum hybrid (HHA) and Galanthus nivalis (GNA) are 50,000-D tetramers showing specificity for alpha-(1,3) and/or alpha-(1,6)-mannose oligomers. They inhibit HIV-1 infection at a 50% effective concentration of 0.2 to 0.3 microg/ml. Escalating HHA or GNA concentrations (up to 500 microg/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.
Balzarini
Jan
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. jan.balzarini@rega.kuleuven.ac.be
Van Laethem
Kristel
K
Hatse
Sigrid
S
Froeyen
Matheus
M
Van Damme
Els
E
Bolmstedt
Anders
A
Peumans
Willy
W
De Clercq
Erik
E
Schols
Dominique
D
D019380:Anti-HIV Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D027801:Galanthus; D006031:Glycosylation / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D019668:Liliaceae; D037241:Mannose-Binding Lectins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D037241:Mannose-Binding Lectins