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

Liwei Cao, Matthias Pauthner, Raiees Andrabi, Kimmo Rantalainen, Zachary Berndsen, Jolene K. Diedrich, Sergey Menis, Devin Sok, Raiza Bastidas, Sung-Kyu Robin Park, Claire M. Delahunty, Lin He, Javier Guenaga, Richard T. Wyatt, William R. Schief, Andrew B. Ward, John R. Yates, Dennis R. Burton and James C. Paulson ()
Additional contact information
Liwei Cao: The Scripps Research Institute
Matthias Pauthner: The Scripps Research Institute
Raiees Andrabi: The Scripps Research Institute
Kimmo Rantalainen: The Scripps Research Institute
Zachary Berndsen: The Scripps Research Institute
Jolene K. Diedrich: The Scripps Research Institute
Sergey Menis: The Scripps Research Institute
Devin Sok: The Scripps Research Institute
Raiza Bastidas: The Scripps Research Institute
Sung-Kyu Robin Park: The Scripps Research Institute
Claire M. Delahunty: The Scripps Research Institute
Lin He: The Scripps Research Institute
Javier Guenaga: The Scripps Research Institute
Richard T. Wyatt: The Scripps Research Institute
William R. Schief: The Scripps Research Institute
Andrew B. Ward: The Scripps Research Institute
John R. Yates: The Scripps Research Institute
Dennis R. Burton: The Scripps Research Institute
James C. Paulson: The Scripps Research Institute

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06121-4

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