Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120.
During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope (Env) with various receptors, we assessed the inhibitory properties of various anti-Env monoclonal antibodies (mAbs) in binding assays. To assist in detecting Env in attachment assays, we generated Fc fusions of full-length wild-type gp120 and several variable loop-deleted gp120s. Through investigation of the inhibition of Env binding to cell lines expressing CD4, CCR5, DC-SIGN, syndecans or combinations thereof, we found that the broadly neutralizing mAb, 2G12, directed to a unique carbohydrate epitope of gp120, inhibited Env-CCR5 binding, partially inhibited Env-DC-SIGN binding, but had no effect on Env-syndecan association. Furthermore, 2G12 inhibited Env attachment to primary monocyte-derived dendritic cells, that expressed CD4 and CCR5 primary HIV receptors, as well as DC-SIGN, and suggested that the dual activities of 2G12 could be valuable in vivo for inhibiting initial virus dissemination and propagation.
Binley
James M
JM
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego CA 92121, USA. jbinley@tpims.org
Ngo-Abdalla
Stacie
S
Moore
Penny
P
Bobardt
Michael
M
Chatterji
Udayan
U
Gallay
Philippe
P
Burton
Dennis R
DR
Wilson
Ian A
IA
Elder
John H
JH
de Parseval
Aymeric
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D006367:HeLa Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D019812:Heparan Sulfate Proteoglycans; D037181:Lectins, C-Type; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D015728:Receptors, HIV; D011993:Recombinant Fusion Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin