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

Author

Listed:
  • Liwei Cao

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Matthias Pauthner

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Raiees Andrabi

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Kimmo Rantalainen

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Zachary Berndsen

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Jolene K. Diedrich

    (The Scripps Research Institute)

  • Sergey Menis

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Devin Sok

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Raiza Bastidas

    (The Scripps Research Institute
    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
    The Scripps Research Institute)

  • Richard T. Wyatt

    (The Scripps Research Institute
    The Scripps Research Institute)

  • William R. Schief

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Andrew B. Ward

    (The Scripps Research Institute
    The Scripps Research Institute)

  • John R. Yates

    (The Scripps Research Institute)

  • Dennis R. Burton

    (The Scripps Research Institute
    The Scripps Research Institute
    Ragon Institute of MGH, MIT and Harvard)

  • James C. Paulson

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

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.

Suggested Citation

  • 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, 2018. "Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06121-4
    DOI: 10.1038/s41467-018-06121-4
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    Cited by:

    1. Annemart Koornneef & Kanika Vanshylla & Gijs Hardenberg & Lucy Rutten & Nika M. Strokappe & Jeroen Tolboom & Jessica Vreugdenhil & Karin Feddes-de Boer & Aditya Perkasa & Sven Blokland & Judith A. Bur, 2024. "CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.

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