Discovery of O-Linked Carbohydrate on HIV-1 Envelope and Its Role in Shielding against One Category of Broadly Neutralizing Antibodies

Zachary A. Silver, Aristotelis Antonopoulos, Stuart M. Haslam, Anne Dell, Gordon M. Dickinson, Michael S. Seaman, Ronald C. Desrosiers

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Approximately 50% of the mass of the Envelope (Env) glycoprotein surface subunit (gp120) of human immunodeficiency virus type 1 (HIV-1) is composed of N-linked carbohydrate. Until now, the dogma has been that HIV-1 lacks O-linked carbohydrate on Env. Here we show that a subset of patient-derived HIV-1 isolates contain O-linked carbohydrate on the variable 1 (V1) domain of Env gp120. We demonstrate the presence of this O-glycosylation both on virions and on gp120 expressed as a secreted protein. Further, we establish that these O-linked glycans can confer a more than 1,000-fold decrease in neutralization sensitivity (IC50) to V3-glycan broadly neutralizing antibodies. These findings uncover a structural modification to the HIV-1 Env and suggest a functional role in promoting viral escape from one category of broadly neutralizing antibodies.

Original languageEnglish (US)
Pages (from-to)1862-1869.e4
JournalCell Reports
Volume30
Issue number6
DOIs
StatePublished - Feb 11 2020

Keywords

  • Envelope
  • HIV-1
  • O-glycosylation
  • V1 domain
  • broadly neutralizing antibodies
  • escape mechanism
  • gp120
  • immune evasion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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