title: Chinks in the armor of the HIV-1 Envelope glycan shield: Implications for immune escape from anti-glycan broadly neutralizing antibodies.
abstract: Glycans on HIV-1 Envelope serve multiple functions including blocking epitopes from antibodies. We show that removal of glycan 301, a major target of anti-V3/glycan antibodies, has substantially different effects in two viruses. While glycan 301 on Du156.12 blocks epitopes commonly recognized by sera from chronically HIV-1-infected individuals, it does not do so on CAP45.G3, suggesting that removing the 301 glycan has a smaller effect on the integrity of the glycan shield in CAP45.G3. Changes in sensitivity to broadly neutralizing monoclonal antibodies suggest that the interaction between glycan 301 and the CD4 binding site differ substantially between these 2 viruses. Molecular modeling suggests that removal of glycan 301 likely exposes a greater surface area of the V3 and C4 regions in Du156.12. Our data indicate that the contribution of the 301 glycan to resistance to common neutralizing antibodies varies between viruses, allowing for easier selection for its loss in some viruses.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Thandeka
authors.initials: T
authors.lastname: Moyo
authors.affiliation: South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa.
authors.forename: Roux-Cil
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Reyaaz
authors.initials: R
authors.lastname: Davids
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa.
authors.forename: Zarinah
authors.initials: Z
authors.lastname: Sonday
authors.affiliation: University of the Witwatersrand and National Institute for Communicable Disease, Johannesburg, South Africa.
authors.forename: Penny L
authors.initials: PL
authors.lastname: Moore
authors.affiliation: South African National Bioinformatics Institute, University of the Western Cape, Cape Town, South Africa.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Travers
authors.affiliation: Computational Biology Division, Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Natasha T
authors.initials: NT
authors.lastname: Wood
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa. Electronic address: jeffrey.dorfman@uct.ac.za.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Dorfman
mesh_terms: D020816:Amino Acid Motifs; D057134:Antibodies, Neutralizing / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides
keywords: HIV-1; HIV-1 selection pressure; Neutralizing antibodies; V3 glycans; V3 loop