CD4 incorporation into HIV-1 viral particles exposes envelope epitopes recognized by CD4-induced antibodies

Shilei Ding, Romain Gasser, Gabrielle Gendron-Lepage, Halima Medjahed, William D. Tolbert, Joseph Sodroski, Marzena Pazgier, Andrés Finzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


CD4 downregulation on infected cells is a highly conserved function of primate lentiviruses. It has been shown to positively impact viral replication by a variety of mechanisms, including enhanced viral release and infectivity, decrease of cell reinfection, and protection from antibody-dependent cellular cytotoxicity (ADCC), which is often mediated by antibodies that require CD4 to change envelope (Env) conformation. Here, we report that incorporation of CD4 into HIV-1 viral particles affects Env conformation resulting in the exposure of occluded epitopes recognized by CD4-induced antibodies. This translates into enhanced neutralization susceptibility by these otherwise nonneutralizing antibodies but is prevented by the HIV-1 Nef accessory protein. Altogether, these findings suggest that another functional consequence of Nef-mediated CD4 downregulation is the protection of viral particles from neutralization by commonly elicited CD4-induced antibodies. IMPORTANCE It has been well established that Env-CD4 complexes expose epitopes recognized by commonly elicited CD4-induced antibodies at the surface of HIV-1- infected cells, rendering them vulnerable to ADCC responses. Here, we show that CD4 incorporation has a profound impact on Env conformation at the surface of viral particles. Incorporated CD4 exposes CD4-induced epitopes on Env, rendering HIV-1 susceptible to neutralization by otherwise nonneutralizing antibodies.

Original languageEnglish
Article numbere01403-19
JournalJournal of Virology
Issue number22
StatePublished - 1 Nov 2019
Externally publishedYes


  • CD4
  • CD4-induced antibodies
  • Cold inactivation
  • Env
  • Env conformation
  • HIV-1
  • HIV-1
  • Incorporation
  • Neutralization
  • Nonneutralizing antibodies
  • Virus capture assay


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