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J Virol. 2017 Aug 24;91(18). pii: e00700-17. doi: 10.1128/JVI.00700-17. Print 2017 Sep 15.

HIV-1 Env- and Vpu-Specific Antibody-Dependent Cellular Cytotoxicity Responses Associated with Elite Control of HIV.

Author information

1
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia.
2
Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
3
Department of Immunology, Monash University Central Clinical School, Melbourne, Victoria, Australia.
4
Department of Pathology, The University of Melbourne, Victoria, Australia.
5
Kirby Institute, University of New South Wales, Sydney, Australia.
6
St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.
7
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia skent@unimelb.edu.au.
8
Melbourne Sexual Health Clinic and Infectious Diseases Department, Alfred Hospital, Monash University Central Clinical School, Carlton, Victoria, Australia.
9
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, Australia.

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.IMPORTANCE Understanding immune responses associated with elite control of HIV may aid the development of immunotherapeutic and vaccine strategies for controlling HIV infection. Env is a major HIV protein target of functional antibody responses that are heightened in ECs. Interestingly, EC antibodies also target Vpu, an accessory protein crucial to HIV, which degrades CD4 and antagonizes tetherin. Antibodies specific to Vpu are a common feature of the immune response of ECs that may prove to be of functional importance to the design of improved ADCC-based immunotherapy and preventative HIV vaccines.

KEYWORDS:

ADCC; FcγR; Vpu; elite controller

PMID:
28701393
PMCID:
PMC5571238
DOI:
10.1128/JVI.00700-17
[Indexed for MEDLINE]
Free PMC Article

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