title: Epitope target structures of Fc-mediated effector function during HIV-1 acquisition.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: George K
authors.initials: GK
authors.lastname: Lewis
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guan
authors.forename: Roberta
authors.initials: R
authors.lastname: Kamin-Lewis
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sajadi
authors.forename: Marzena
authors.initials: M
authors.lastname: Pazgier
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Devico
mesh_terms: D000939:Epitopes; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D000939:Epitopes; D015483:HIV Antibodies; D007141:Immunoglobulin Fc Fragments; D054299:env Gene Products, Human Immunodeficiency Virus