SPECTRUM OF HIV ANTIBODIES IN VACCINE AND DISEASE: Edited by Georgia D. Tomaras and David C. MontefioriEpitope target structures of Fc-mediated effector function during HIV-1 acquisitionLewis, George K.a; Guan, Yongjuna; Kamin-Lewis, Robertaa; Sajadi, Mohammadb; Pazgier, Marzenaa; Devico, Anthony L.aAuthor Information aDivision of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine bDivision of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA Correspondence to George K. Lewis, PhD, Division of Basic Science and Vaccine Research, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA. Tel: +1 410 706 4688; e-mail: [email protected] Current Opinion in HIV and AIDS: May 2014 - Volume 9 - Issue 3 - p 263-270 doi: 10.1097/COH.0000000000000055 Buy Metrics Abstract Purpose of review This review analyzes recent studies suggesting that highly conserved epitopes in the HIV-1 Env trimer are targets of potentially protective nonneutralizing antibodies that mediate antibody-dependent cellular cytotoxicity. Recent findings Recent studies in both non-human primates and humans suggest that nonneutralizing antibodies play a role in blocking infection with hybrid simian HIV (SHIV)/simian immunodeficiency virus (SIV) or HIV-1 by Fc-mediated effector function, in particular antibody-dependent cellular cytotoxicity. Further, several studies implicate highly conserved epitopes in the C1 region of gp120 as targets of these antibodies. However, these suggestions are controversial, as passive immunization studies do not indicate that such antibodies can block acquisition in non-human primates. Potential reasons for this discrepancy are discussed in the structural context of potent antibody-dependent cellular cytotoxicity epitopes on target cells during the narrow window of opportunity when antibodies can block HIV-1 acquisition. Summary Cumulative evidence suggests that, in addition to virus neutralization, Fc-mediated effector responses to highly conserved epitopes in the HIV-1 trimer play distinct as well as overlapping roles in blocking HIV-1 acquisition. Evidence will be discussed as to whether nonneutralizing antibodies specific for epitopes on the HIV-1 Env trimer that become exposed during viral entry contribute significantly to blocking HIV-1 acquisition. © 2014 Lippincott Williams & Wilkins, Inc.