HIV-1 Env- and Vpu-specific antibody-dependent cellular cytotoxicity responses associated with elite control of HIV

Vijaya Madhavi, Bruce D. Wines, Janaki Amin, Sean Emery, Ester Lopez, Anthony Kelleher, Rob J. Center, P. Mark Hogarth, Amy W. Chung, Stephen J. Kent, Ivan Stratov, ENCORE1 Study Group, Sydney LTNP Study Group

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28 Citations (Scopus)

Abstract

Studying HIV-infected individuals who control HIV replication (elite controllers [ECs]) enables exploration of effective anti-HIV immunity. HIV Env-specific and non- Env-specific antibody-dependent cellular cytotoxicity (ADCC) may contribute to protection from progressive HIV infection, but the evidence is limited. We recruited 22 ECs and matched them with 44 viremic subjects. HIV Env- and Vpu-specific ADCC responses in sera were studied using a novel enzyme-linked immunosorbent assay (ELISA)-based dimeric recombinant soluble FcγRIIIa (rsFcγRIIIa)-binding assay, surface plasmon resonance, antibody-dependent natural killer (NK) cell activation assays, and ADCC-mediated killing assays. ECs had higher levels of HIV Env-specific antibodies capable of binding FcγRIIIa, activating NK cells, and mediating granzyme B activity (all P < 0.01) than viremic subjects. ECs also had higher levels of antibodies against a C-terminal 13-mer Vpu peptide capable of mediating FcγRIIIa binding and NK cell activation than viremic subjects (both P < 0.05). Our data associate Env-specific and Vpu epitope-specific ADCC in effective immune responses against HIV among ECs. Our findings have implications for understanding the role of ADCC in HIV control.

Original languageEnglish
Article numbere00700-17
Number of pages16
JournalJournal of Virology
Volume91
Issue number18
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • ADCC
  • Elite controller
  • FcγR
  • Vpu

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