Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers
Laura K. Pritchard,
Snezana Vasiljevic,
Gabriel Ozorowski,
Gemma E. Seabright,
Albert Cupo,
Rajesh Ringe,
Helen J. Kim,
Rogier W. Sanders,
Katie J. Doores,
Dennis R. Burton,
Ian A. Wilson,
Andrew B. Ward,
John P. Moore,
Max Crispin
Affiliations
Laura K. Pritchard
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Snezana Vasiljevic
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Gabriel Ozorowski
Department of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and the collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Gemma E. Seabright
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
Albert Cupo
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, NY 10021, USA
Rajesh Ringe
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, NY 10021, USA
Helen J. Kim
Department of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and the collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Rogier W. Sanders
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, NY 10021, USA
Katie J. Doores
King’s College London School of Medicine at Guy’s, King’s and St. Thomas’ Hospitals, Guy’s Hospital, Great Maze Pond, London SE1 9RT, UK
Dennis R. Burton
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA
Ian A. Wilson
Department of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and the collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Andrew B. Ward
Department of Integrative Structural and Computational Biology, IAVI Neutralizing Antibody Center and the collaboration for AIDS Vaccine Discovery, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
John P. Moore
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, NY 10021, USA
Max Crispin
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
A highly glycosylated, trimeric envelope glycoprotein (Env) mediates HIV-1 cell entry. The high density and heterogeneity of the glycans shield Env from recognition by the immune system, but paradoxically, many potent broadly neutralizing antibodies (bNAbs) recognize epitopes involving this glycan shield. To better understand Env glycosylation and its role in bNAb recognition, we characterized a soluble, cleaved recombinant trimer (BG505 SOSIP.664) that is a close structural and antigenic mimic of native Env. Large, unprocessed oligomannose-type structures (Man8-9GlcNAc2) are notably prevalent on the gp120 components of the trimer, irrespective of the mammalian cell expression system or the bNAb used for affinity purification. In contrast, gp41 subunits carry more highly processed glycans. The glycans on uncleaved, non-native oligomeric gp140 proteins are also highly processed. A homogeneous, oligomannose-dominated glycan profile is therefore a hallmark of a native Env conformation and a potential Achilles’ heel that can be exploited for bNAb recognition and vaccine design.
