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Related Experiment Video

Updated: Aug 22, 2025

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HIV-1 Vpu restricts Fc-mediated effector functions in vivo.

Jérémie Prévost1, Sai Priya Anand2, Jyothi Krishnaswamy Rajashekar3

  • 1Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H2X 0A9, Canada.

Cell Reports
|November 9, 2022
PubMed
Summary

Non-neutralizing antibodies (nnAbs) fight HIV-1 by triggering cell killing. Restoring the Vpu protein in HIV-1 prevents nnAbs from eliminating infected cells, highlighting Vpu's role in immune evasion.

Keywords:
ADCCCD4 mimeticsCP: ImmunologyEnvFc-effector functionsHIV-1Vpubroadly neutralizing antibodieshumanized miceimmune evasionnon-neutralizing antibodies

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Area of Science:

  • Immunology
  • Virology
  • Vaccinology

Background:

  • Non-neutralizing antibodies (nnAbs) mediate antibody-dependent cellular cytotoxicity (ADCC) against HIV-1-infected cells.
  • nnAbs were identified as a correlate of protection in the RV144 vaccine trial.
  • Fc-mediated effector functions of nnAbs alter HIV-1 infection in vivo, particularly with Vpu-defective viruses.

Purpose of the Study:

  • To investigate the role of HIV-1 Vpu protein in nnAbs-mediated ADCC.
  • To determine if Vpu expression affects the susceptibility of HIV-1-infected cells to nnAbs.
  • To assess the impact of Vpu on the efficacy of nnAbs in vivo.

Main Methods:

  • Restoring Vpu expression in HIV-1-infected cells and assessing nnAbs recognition and ADCC.
  • Administering nnAbs to humanized mice infected with either Vpu-defective or wild-type HIV-1.
  • Using CD4-mimetics to expose viral envelope glycoprotein (Env) epitopes and evaluate nnAbs sensitivity.

Main Results:

  • Restoring Vpu expression significantly reduces nnAbs recognition and renders infected cells resistant to ADCC.
  • nnAbs administration reduced viral loads in mice infected with Vpu-defective HIV-1 but not wild-type HIV-1.
  • CD4-mimetics treatment sensitized wild-type HIV-1 to nnAbs Fc-effector functions.

Conclusions:

  • HIV-1 Vpu plays a critical role in evading humoral immune responses by downregulating CD4 and preventing nnAbs-mediated ADCC.
  • Vpu expression is a key factor determining the efficacy of nnAbs against HIV-1 infection.
  • Targeting Vpu-mediated immune evasion strategies could enhance the effectiveness of antibody-based HIV-1 therapies and vaccines.