Concanavalin A binding to HIV envelope protein is less sensitive to mutations in glycosylation sites than monoclonal antibody 2G12.
Many mannose-binding proteins inhibit divergent strains of human immunodeficiency virus type 1 (HIV-1) in in vitro models of viral infectivity, suggesting that targeting mannose residues in vaccine applications might offset the strain restriction typically observed in antibody responses to HIV vaccine preparations. Concanavalin A (ConA) behaves like neutralizing antibodies that do not interfere with CD4 binding of gp120 but rather with later events in virus entry. The design of mannose-based vaccines, therefore, depends on understanding the mode of binding of ConA to the envelope protein in comparison with other mannose-binding proteins. Here, we further compare the binding affinity and fine specificity of ConA for the envelope protein to that of the human antibody 2G12. The 2G12 antibody is of unusual structure recognizing a cluster of 12 linked mannose residues associated with Man9GlcNAc2. Molecular structure comparison for Man9GlcNAc2 recognition by ConA and 2G12 indicates that 2G12 has a more restricted specificity to high mannose glycans of gp120 which correlates with kinetic analysis assessed by surface plasmon resonance (SPR) and ConA inhibits 2G12 binding to gp120 but 2G12 does not inhibit ConA binding to gp120. ConA binding to Env proteins from four different HIV strains proves significantly less sensitive to mutations in the glycosylation sites than 2G12 binding to the proteins. Thus, antibodies directed toward mannose epitopes reactive with ConA may prove to be more effective in the long run to thwart HIV infection and transmission.
Pashov
Anastas
A
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
MacLeod
Stewart
S
Saha
Rinku
R
Perry
Marty
M
VanCott
Thomas C
TC
Kieber-Emmons
Thomas
T
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002240:Carbohydrate Sequence; D003208:Concanavalin A / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000235:genetics; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008358:Mannose / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D003208:Concanavalin A; D008358:Mannose