title: An N-glycan within the human immunodeficiency virus type 1 gp120 V3 loop affects virus neutralization.
abstract: Carbohydrate side chains of envelope glycoproteins of HIV-1 and other viruses have been postulated to interfere with binding of neutralizing antibodies. So far, however, little evidence for interference of specific N-glycans with virus neutralization has been provided. We used four infectious HIV-1 molecular clones chimeric for their gp 120 V3 domains to study the influence on HIV-1 neutralization of an N-glycan localized within the V3 loop. Two clones lacking the 301N-glycan were at least 8-fold more sensitive to neutralization by two V3-specific monoclonal antibodies (MAbs) and 2- to 10-fold more sensitive to neutralization by a CD4-binding-site-specific human MAb than two HIV-1 clones glycosylated at this site. The affinity of the V3 MAbs for soluble gp120 of the four clones was similar. However, a decreased binding of these MAbs to the gp120 of the two 301N-glycosylated clones was observed when the majority of gp120 was virion-associated during the initial binding step. These findings indicate that the 301N-glycan may interfere with the binding of neutralizing antibodies by limiting the accessibility of neutralization sites or by inducing conformational changes in the HIV-1 gp120 molecule.
authors.affiliation: Department of Virology, University of Amsterdam, Academic Medical Center, The Netherlands.
authors.forename: N K
authors.initials: NK
authors.lastname: Back
authors.forename: L
authors.initials: L
authors.lastname: Smit
authors.forename: J J
authors.initials: JJ
authors.lastname: De Jong
authors.forename: W
authors.initials: W
authors.lastname: Keulen
authors.forename: M
authors.initials: M
authors.lastname: Schutten
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: M
authors.initials: M
authors.lastname: Tersmette
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000276:immunology*; D003001:Cloning, Molecular; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011134:Polysaccharides / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins