title: Beyond Viral Neutralization.
abstract: It has been known for more than 30 years that HIV-1 infection drives a very potent B cell response resulting in the production of anti-HIV-1 antibodies targeting several viral proteins, particularly its envelope glycoproteins (Env). Env epitopes are exposed on the surfaces of viral particles and infected cells where they are targets of potentially protective antibodies. These antibodies can interdict infection by neutralization and there is strong evidence suggesting that Fc-mediated effector function can also contribute to protection. Current evidence suggests that Fc-mediated effector function plays a role in protection against infection by broadly neutralizing antibodies and it might be important for protection by non-neutralizing antibodies. Fc-mediated effector function includes diverse mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), antibody-mediated complement activation, antibody-dependent cellular phagocytosis, antibody-dependent cell-mediated virus inhibition, antibody-mediated trancytosis inhibition, and antibody-mediated virus opsonization. All these functions could be beneficial in fighting viral infections, including HIV-1. In this perspective, we discuss the latest developments in ADCC research discussed at the HIVR4P satellite session on non-neutralizing antibodies, with emphasis on the mechanisms of ADCC resistance used by HIV-1, the structural basis of epitopes recognized by antibodies that mediate ADCC, natural killer-cell education and ADCC, and murine models to study ADCC against HIV-1.
authors.affiliation: 1 Division of Vaccine Research of Institute of Human Virology, University of Maryland School of Medicine , Baltimore, Maryland.|2 Department of Microbiology and Immunology, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: George K
authors.initials: GK
authors.lastname: Lewis
authors.affiliation: 1 Division of Vaccine Research of Institute of Human Virology, University of Maryland School of Medicine , Baltimore, Maryland.|3 Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Pazgier
authors.affiliation: 4 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison , Madison, Wisconsin.|5 Wisconsin National Primate Research Center, University of Wisconsin-Madison , Madison, Wisconsin.
authors.forename: David T
authors.initials: DT
authors.lastname: Evans
authors.affiliation: 6 Duke Human Vaccine Institute, Duke University Medical Center , Durham, North Carolina.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: 7 Laboratory of Molecular Genetics and Immunology, The Rockefeller University , New York, New York.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Bournazos
authors.affiliation: 8 Department of Microbiology and Immunology, University of Melbourne , Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia .
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.affiliation: 9 Research Institute of the McGill University Health Centre, Division of Experimental Medicine, McGill University , Quebec, Canada .
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
authors.affiliation: 10 Centre de Recherche du CHUM, Université de Montréal , Quebec, Canada .|11 Department of Microbiology, Infectiology and Immunology, Université de Montréal , Quebec, Canada .|12 Department of Microbiology and Immunology, McGill University , Quebec, Canada .
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D003167:Complement Activation; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D010587:Phagocytosis
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: ADCC; Env; Fc; HIV-1; KIR; NK; humanized mouse models; neutralization; non-neutralizing antibodies