Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer

• Published in: Nature communications Vol. 9; no. 1; pp. 3693 - 14
• Main Authors: Cao, Liwei, Pauthner, Matthias, Andrabi, Raiees, Rantalainen, Kimmo, Berndsen, Zachary, Diedrich, Jolene K., Menis, Sergey, Sok, Devin, Bastidas, Raiza, Park, Sung-Kyu Robin, Delahunty, Claire M., He, Lin, Guenaga, Javier, Wyatt, Richard T., Schief, William R., Ward, Andrew B., Yates, John R., Burton, Dennis R., Paulson, James C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.09.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 631/250/590; 631/92/221; 692/699/255/1901; 82/58; Antibodies; Antibodies, Neutralizing - immunology; Antigenicity; Epitopes; Epitopes - immunology; Glycoproteins; Glycosylation; HIV; HIV Antibodies - immunology; HIV-1 - immunology; HIV-1 - metabolism; HIV-1 - pathogenicity; Human immunodeficiency virus; Humanities and Social Sciences; Humans; multidisciplinary; N-glycans; Polysaccharides; Polysaccharides - immunology; Polysaccharides - metabolism; Protein Multimerization; Science; Science (multidisciplinary); Trimers; Vaccination; Vaccines; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06121-4

As the sole target of broadly neutralizing antibodies (bnAbs) to HIV, the envelope glycoprotein (Env) trimer is the focus of vaccination strategies designed to elicit protective bnAbs in humans. Because HIV Env is densely glycosylated with 75–90 N-glycans per trimer, most bnAbs use or accommodate them in their binding epitope, making the glycosylation of recombinant Env a key aspect of HIV vaccine design. Upon analysis of three HIV strains, we here find that site-specific glycosylation of Env from infectious virus closely matches Envs from corresponding recombinant membrane-bound trimers. However, viral Envs differ significantly from recombinant soluble, cleaved (SOSIP) Env trimers, strongly impacting antigenicity. These results provide a benchmark for virus Env glycosylation needed for the design of soluble Env trimers as part of an overall HIV vaccine strategy. HIV envelope (Env) is a potential vaccine antigen and its N-glycans are part of the epitope of broadly neutralizing antibodies. Here, the authors show that glycosylation of Env from infectious virus closely matches Env from recombinant membrane-bound trimers, while it differs significantly from recombinant soluble, cleaved Env trimers.