The HIV-1 envelope glycoprotein structure: nailing down a moving target

Immunol Rev. 2017 Jan;275(1):21-32. doi: 10.1111/imr.12507.


Structure determination of the HIV-1 envelope glycoprotein (Env) presented a number of challenges, but several high-resolution structures have now become available. In 2013, cryo-EM and x-ray structures of soluble, cleaved SOSIP Env trimers from the clade A BG505 strain provided the first glimpses into the Env trimer fold as well as more the variable regions. A recent cryo-EM structure of a native full-length trimer without any stabilizing mutations had the same core structure, but revealed new insights and features. A more comprehensive and higher resolution understanding of the glycan shield has also emerged, enabling a more complete representation of the Env glycoprotein structure. Complexes of Env trimers with broadly neutralizing antibodies have surprisingly illustrated that most of the Env surface can be targeted in natural infection and that the neutralizing epitopes are almost all composed of both peptide and glycan components. These structures have also provided further evidence of the inherent plasticity of Env and how antibodies can exploit this flexibility by perturbing or even stabilizing the trimer to facilitate neutralization. These breakthroughs have stimulated further design and stabilization of Env trimers as well as other platforms to generate trimers that now span multiple subtypes. These Env trimers when used as immunogens, have led to the first vaccine-induced neutralizing antibodies for structural and functional analyses.

Keywords: HIV envelope structure; cryo-electron microscopy; epitope mapping; glycan shield; structure-based vaccine design; x-ray crystallography.

Publication types

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

MeSH terms

  • AIDS Vaccines / immunology*
  • Animals
  • Antibodies, Neutralizing / metabolism
  • Crystallography, X-Ray
  • Epitopes / chemistry*
  • Epitopes / immunology
  • HIV Antibodies / metabolism
  • HIV Antigens / chemistry*
  • HIV Antigens / immunology
  • HIV Infections / immunology*
  • HIV-1 / chemistry*
  • HIV-1 / immunology
  • Humans
  • Protein Conformation
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / immunology


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Antigens
  • Viral Envelope Proteins