Antibody-induced internalization of HIV-1 Env proteins limits surface expression of the closed conformation of Env

Sai Priya Anand, Jonathan R. Grover, William D. Tolbert, Jérémie Prévost, Jonathan Richard, Shilei Ding, Sophie Baril, Halima Medjahed, David T. Evans, Marzena Pazgier, Walther Mothes, Andrés Finzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


To minimize immune responses against infected cells, HIV-1 limits the surface expression of its envelope glycoprotein (Env). Here, we demonstrate that this mechanism is specific for the Env conformation and affects the efficiency of antibody-dependent cellular cytotoxicity (ADCC). Using flow cytometry and confocal microscopy, we show that broadly neutralizing antibodies (bNAbs) targeting the “closed” conformation of Env induce its internalization from the surface. In contrast, non-neutralizing antibodies (nNAbs) are displayed on the cell surface for prolonged period of times. The bNAb-induced Env internalization can be decreased by blocking dynamin function, which translates into higher susceptibilities of infected cells to ADCC. Our results suggest that antibody-mediated Env internalization is a mechanism used by HIV-1 to evade immune responses against the “closed” conformation of Env expressed on HIV-1-infected cells. IMPORTANCE HIV-1 has evolved to acquire several strategies to limit the exposure of its envelope glycoproteins (Env) on the surface of infected cells. In this study, we show that antibody-induced Env internalization is conformation specific and reduces the susceptibility of infected cells to antibody-dependent cellular cytotoxicity (ADCC). Thus, a better understanding of this mechanism might help develop antibodies with improved capacities to mediate ADCC.

Original languageEnglish
Article numbere0029319
JournalJournal of Virology
Issue number11
StatePublished - 2019
Externally publishedYes


  • ADCC
  • BNAbs
  • Dynamin
  • Env
  • Env conformation
  • HIV-1
  • Internalization
  • Nonneutralizing antibodies


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