An N-glycan within the human immunodeficiency virus type 1 gp120 V3 loop affects virus neutralization.
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.
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N K
NK
Department of Virology, University of Amsterdam, Academic Medical Center, The Netherlands.
Smit
L
L
De Jong
J J
JJ
Keulen
W
W
Schutten
M
M
Goudsmit
J
J
Tersmette
M
M
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
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins