BIOMAT Database Logo BIOMAT Database Logo

Probability of N332 glycan occupancy on HIV-1 gp120 modulates sensitivity to broadly neutralizing antibodies. 2016

Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
aDepartment of Medical Microbiology bDepartment of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam cJanssen Pharmaceuticals, Leiden, The Netherlands dDepartment of Microbiology and Immunology, Weill Medical College, Cornell University, New York City, New York, USA.

The glycan shield of the HIV-1 envelope glycoprotein complex (Env), in particular the glycan at position 332 in gp120, is frequently targeted by broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals. We investigated the role of the second amino acid position of the N332 glycosylation motif Asn-X-Ser in HIV-1 evolution and neutralization sensitivity. Viral variants harbouring glycosylation motifs with different probabilities of glycan occupancy were tested for their sensitivity to a subset of N332-dependent bNAbs. Furthermore, longitudinal Env sequences of 37 HIV-1 infected individuals were used to analyse the evolution of the N332 glycosylation motif within these individuals. Finally, early Env sequences from 31 historical and 21 contemporaneous seroconverters were compared to analyse this evolution on a population level. Viral variants with a higher probability of N332 occupancy were more sensitive to neutralization by some N332-dependent bNAbs. Furthermore, the longitudinal analyses revealed an increase in probability of glycan occupancy of the N332 site over time, both within patients, and at the population level over the course of 20 years of HIV-1 epidemic. These observations suggest that modulation of N332 glycan occupancy by the second amino acid position of the canonical glycosylation motif Asn-X-Ser plays a previously unappreciated role in viral escape from immune responses, and should be considered in Env-based vaccine design.

UI MeSH Term Description Entries
D011134 Polysaccharides Long chain polymeric CARBOHYDRATES composed of MONOSACCHARIDES linked by glycosidic bonds. Glycan,Glycans,Polysaccharide
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015483 HIV Antibodies Antibodies reactive with HIV ANTIGENS. AIDS Antibodies,HIV-Associated Antibodies,HTLV-III Antibodies,HTLV-III-LAV Antibodies,LAV Antibodies,Lymphadenopathy-Associated Antibodies,T-Lymphotropic Virus Type III Antibodies, Human,HIV Associated Antibodies,HTLV III Antibodies,HTLV III LAV Antibodies,Lymphadenopathy Associated Antibodies,T Lymphotropic Virus Type III Antibodies, Human,Antibodies, AIDS,Antibodies, HIV,Antibodies, HIV Associated,Antibodies, HIV-Associated,Antibodies, HTLV III,Antibodies, HTLV-III,Antibodies, HTLV-III-LAV,Antibodies, LAV,Antibodies, Lymphadenopathy Associated,Antibodies, Lymphadenopathy-Associated
D015699 HIV Envelope Protein gp120 External envelope protein of the human immunodeficiency virus which is encoded by the HIV env gene. It has a molecular weight of 120 kDa and contains numerous glycosylation sites. Gp120 binds to cells expressing CD4 cell-surface antigens, most notably T4-lymphocytes and monocytes/macrophages. Gp120 has been shown to interfere with the normal function of CD4 and is at least partly responsible for the cytopathic effect of HIV. Envelope Glycoprotein gp120, HIV,HTLV-III gp120,env Protein gp120, HIV,gp120(HIV),HIV Envelope Glycoprotein gp120,gp120 Envelope Glycoprotein, HIV,HTLV III gp120,gp120, HTLV-III
D057131 Immune Evasion Methods used by pathogenic organisms to evade a host's immune system. Evasion, Immune,Evasions, Immune,Immune Evasions
D057134 Antibodies, Neutralizing Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus. Neutralizing Antibodies,Antibody, Neutralizing,Neutralizing Antibody

Related Publications

Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Alternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan.
November 2023, bioRxiv : the preprint server for biology,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Alternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan.
March 2024, mBio,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
HIV-1 clade C escapes broadly neutralizing autologous antibodies with N332 glycan specificity by distinct mechanisms.
August 2016, Retrovirology,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.
March 2017, Science translational medicine,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted / founder sensitivity to broadly neutralizing antibodies.
December 2023, bioRxiv : the preprint server for biology,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies.
August 2024, Nature communications,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Broadly neutralizing antibodies to prevent HIV-1.
October 2017, Science (New York, N.Y.),
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Rapid elicitation of a new class of neutralizing N332-glycan independent V3-glycan antibodies against HIV-1 in nonhuman primates.
September 2025, bioRxiv : the preprint server for biology,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Polyfunctionality of broadly neutralizing HIV-1 antibodies.
July 2023, Current opinion in HIV and AIDS,
Tom L G M van den Kerkhof, and Marit J van Gils, and Brigitte D Boeser-Nunnink, and Judith A Burger, and Hanneke Schuitemaker, and Rogier W Sanders
Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies.
June 2015, Nature communications,
Copied contents to your clipboard!