IDEAS home Printed from https://ideas.repec.org/a/plo/ppat00/1009185.html
   My bibliography  Save this article

Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes

Author

Listed:
  • Chitra Upadhyay
  • Roya Feyznezhad
  • Liwei Cao
  • Kun-Wei Chan
  • Kevin Liu
  • Weiming Yang
  • Hui Zhang
  • Jason Yolitz
  • James Arthos
  • Arthur Nadas
  • Xiang-Peng Kong
  • Susan Zolla-Pazner
  • Catarina E Hioe

Abstract

HIV-1 envelope (Env) is a trimer of gp120-gp41 heterodimers, synthesized from a precursor gp160 that contains an ER-targeting signal peptide (SP) at its amino-terminus. Each trimer is swathed by ~90 N-linked glycans, comprising complex-type and oligomannose-type glycans, which play an important role in determining virus sensitivity to neutralizing antibodies. We previously examined the effects of single point SP mutations on Env properties and functions. Here, we aimed to understand the impact of the SP diversity on glycosylation of virus-derived Env and virus neutralization by swapping SPs. Analyses of site-specific glycans revealed that SP swapping altered Env glycan content and occupancy on multiple N-linked glycosites, including conserved N156 and N160 glycans in the V1V2 region at the Env trimer apex and N88 at the trimer base. Virus neutralization was also affected, especially by antibodies against V1V2, V3, and gp41. Likewise, SP swaps affected the recognition of soluble and cell-associated Env by antibodies targeting distinct V1V2 configurations, V3 crown, and gp41 epitopes. These data highlight the contribution of SP sequence diversity in shaping the Env glycan content and its impact on the configuration and accessibility of V1V2 and other Env epitopes.Author summary: HIV-1 Env glycoprotein is produced by a precursor gp160 that has a signal peptide at its N-terminus. The SP is highly diverse among the HIV-1 isolates. This study presents site-specific analyses of N-linked glycosylation on HIV-1 envelope glycoproteins from infectious viruses produced with different envelope signal peptides. We show that signal peptide swapping alters the envelope glycan shield, including the conserved N156 and N160 glycans located in the V1V2 region on the trimer apex, to impact Env recognition and virus neutralization by antibodies. The data offer crucial insights into the role of signal peptide in the interplay between HIV-1 and antibodies and its potential utility to control Env glycosylation in the development of Env-based HIV-1 vaccine.

Suggested Citation

  • Chitra Upadhyay & Roya Feyznezhad & Liwei Cao & Kun-Wei Chan & Kevin Liu & Weiming Yang & Hui Zhang & Jason Yolitz & James Arthos & Arthur Nadas & Xiang-Peng Kong & Susan Zolla-Pazner & Catarina E Hio, 2020. "Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes," PLOS Pathogens, Public Library of Science, vol. 16(12), pages 1-31, December.
  • Handle: RePEc:plo:ppat00:1009185
    DOI: 10.1371/journal.ppat.1009185
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009185
    Download Restriction: no

    File URL: https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009185&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.ppat.1009185?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:ppat00:1009185. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plospathogens (email available below). General contact details of provider: https://journals.plos.org/plospathogens .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.