Patterns of conserved gp120 epitope presentation on attached HIV-1 virions

Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9893-E9902. doi: 10.1073/pnas.1705074114. Epub 2017 Oct 30.


A complete picture of HIV antigenicity during early replication is needed to elucidate the full range of options for controlling infection. Such information is frequently gained through analyses of isolated viral envelope antigens, host CD4 receptors, and cognate antibodies. However, direct examination of viral particles and virus-cell interactions is now possible via advanced microscopy techniques and reagents. Using such methods, we recently determined that CD4-induced (CD4i) transition state epitopes in the HIV surface antigen, gp120, while not exposed on free particles, rapidly become immunoreactive upon virus-cell binding. Here, we use 3D direct stochastic optical reconstruction microscopy (dSTORM) to show that certain CD4i epitopes specific to transition state structures are exposed across the surface of cell-bound virions, thus explaining their immunoreactivity. Moreover, such structures and their marker epitopes are dispersed to regions of virions distal to CD4 contact. We further show that the appearance and positioning of distal CD4i exposures is partially dependent on Gag maturation and intact matrix-gp41 interactions within the virion. Collectively, these observations provide a unique perspective of HIV during early replication. These features may define unique insights for understanding how humoral responses target virions and for developing related antiviral countermeasures.

Keywords: HIV antigenicity; cell attachment; epitope positions; transition state conformation; virion structure.

Publication types

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

MeSH terms

  • CD4 Antigens / metabolism
  • CD4 Lymphocyte Count
  • Cell Line
  • Epitopes / chemistry
  • Epitopes / immunology*
  • HIV Antibodies / immunology
  • HIV Antigens / immunology
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp41 / chemistry
  • HIV Envelope Protein gp41 / immunology
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / chemistry
  • HIV-1 / immunology*
  • Humans
  • Virion / chemistry
  • Virion / immunology*
  • Virion / metabolism
  • Virus Attachment*


  • CD4 Antigens
  • Epitopes
  • HIV Antibodies
  • HIV Antigens
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41