title: Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG.
abstract: HIV-1 viremic controllers (VC) spontaneously control infection without antiretroviral treatment. Several studies indicate that IgG Abs from VCs induce enhanced responses from immune effector cells. Since signaling through Fc-γ receptors (FCGRs) modulate these Ab-driven responses, here we examine if enhanced FCGR activation is a common feature of IgG from VCs. Using an infected cell-based system, we observed that VC IgG stimulated greater FCGR2A and FCGR3A activation as compared with noncontrollers, independent of the magnitude of HIV-specific Ab binding or virus neutralization activities. Multivariate regression analysis showed that enhanced FCGR signaling was a significant predictor of VC status as compared with chronically infected patients (CIP) on highly active antiretroviral therapy (HAART). Unsupervised hierarchical clustering of patient IgG functions primarily grouped VC IgG profiles by enhanced FCGR2A, FCGR3A, or dual signaling activity. Our findings demonstrate that enhanced FCGR signaling is a common and significant predictive feature of VC IgG, with VCs displaying a distinct spectrum of FCGR activation profiles. Thus, profiling FCGR activation may provide a useful method for screening and distinguishing protective anti-HIV IgG responses in HIV-infected patients and in monitoring HIV vaccination regimens.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Alvarez
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Maestre
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Law
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Natasha D
authors.initials: ND
authors.lastname: Durham
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.|Department of Microbiology, University of Concepcion, Concepcion, Chile.
authors.forename: Maria Ines
authors.initials: MI
authors.lastname: Barria
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishii-Watabe
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tada
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Manav
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Hotta
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rodriguez-Caprio
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Fierer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez-Sesma
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.|Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Viviana
authors.initials: V
authors.lastname: Simon
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Chen
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D060467:Disease Resistance; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017452:Receptors, IgG / Q000276:immunology*; D015398:Signal Transduction; D014766:Viremia / Q000276:immunology*
chemical_list: C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D007074:Immunoglobulin G; D017452:Receptors, IgG