Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens

Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13800-5. doi: 10.1073/pnas.1006498107. Epub 2010 Jul 19.


The envelope spike of HIV is one of the most highly N-glycosylated structures found in nature. However, despite extensive research revealing essential functional roles in infection and immune evasion, the chemical structures of the glycans on the native viral envelope glycoprotein gp120--as opposed to recombinantly generated gp120--have not been described. Here, we report on the identity of the N-linked glycans from primary isolates of HIV-1 (clades A, B, and C) and from the simian immunodeficiency virus. MS analysis reveals a remarkably simple and highly conserved virus-specific glycan profile almost entirely devoid of medial Golgi-mediated processing. In stark contrast to recombinant gp120, which shows extensive exposure to cellular glycosylation enzymes (>70% complex type glycans), the native envelope shows barely detectable processing beyond the biosynthetic intermediate Man5GlcNAc2 (<2% complex type glycans). This oligomannose (Man5-9GlcNAc2) profile is conserved across primary isolates and geographically divergent clades but is not reflected in the current generation of gp120 antigens used for vaccine trials. In the context of vaccine design, we also note that Manalpha1-->2Man-terminating glycans (Man6-9GlcNAc2) of the type recognized by the broadly neutralizing anti-HIV antibody 2G12 are 3-fold more abundant on the native envelope than on the recombinant monomer and are also found on isolates not neutralized by 2G12. The Manalpha1-->2Man residues of gp120 therefore provide a vaccine target that is physically larger and antigenically more conserved than the 2G12 epitope itself. This study revises and extends our understanding of the glycan shield of HIV with implications for AIDS vaccine design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • Antigens, Viral / metabolism
  • Cell Line
  • Glycosylation
  • Golgi Apparatus / metabolism
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / chemistry
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • Humans
  • Kinetics
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Oligosaccharides / chemistry
  • Oligosaccharides / immunology*
  • Oligosaccharides / metabolism
  • Polysaccharides / chemistry
  • Polysaccharides / immunology
  • Polysaccharides / metabolism
  • Simian Immunodeficiency Virus / chemistry
  • Simian Immunodeficiency Virus / immunology
  • Simian Immunodeficiency Virus / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism
  • Virion / chemistry
  • Virion / immunology*
  • Virion / metabolism


  • Antigens, Viral
  • HIV Envelope Protein gp120
  • Membrane Glycoproteins
  • Oligosaccharides
  • Polysaccharides
  • Viral Envelope Proteins
  • gp120 protein, Human immunodeficiency virus 1
  • gp120 protein, Simian immunodeficiency virus
  • oligomannoside