Journal
AIDS RESEARCH AND HUMAN RETROVIRUSES
Volume 33, Issue 8, Pages 760-764Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/aid.2016.0299
Keywords
HIV-1; Env; ADCC; non-neutralizing antibodies; neutralization; humanized mouse models; Fc; KIR; NK
Categories
Funding
- NIAID NIH HHS [R01 AI098485, R01 AI129769, R01 AI116274, R01 AI095098, R01 AI121135, P01 AI124912] Funding Source: Medline
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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.
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