The Conformational States of the HIV-1 Envelope Glycoproteins

Trends Microbiol. 2020 Aug;28(8):655-667. doi: 10.1016/j.tim.2020.03.007. Epub 2020 May 14.


During HIV-1 entry into target cells, binding of the virus to host receptors, CD4 and CCR5/CXCR4, triggers serial conformational changes in the envelope glycoprotein (Env) trimer that result in the fusion of the viral and cell membranes. Recent discoveries have refined our knowledge of Env conformational states, allowing characterization of the targets of small-molecule HIV-1 entry inhibitors and neutralizing antibodies, and identifying a novel off-pathway conformation (State 2A). Here, we provide an overview of the current understanding of these conformational states, focusing on (i) the events during HIV-1 entry; (ii) conformational preferences of HIV-1 Env ligands; (iii) evasion of the host antibody response; and (iv) potential implications for therapy and prevention of HIV-1 infection.

Keywords: ADCC; HIV-1 Env; bNAbs; conformational states; entry inhibitors; vaccine design.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • CD4 Antigens / metabolism*
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Humans
  • Immune Evasion / immunology
  • Protein Conformation
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / metabolism*
  • Receptors, Virus / metabolism*
  • Virus Attachment*
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • CCR5 protein, human
  • CD4 Antigens
  • CXCR4 protein, human
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Virus
  • env Gene Products, Human Immunodeficiency Virus