Impact of HIV-1 Envelope Conformation on ADCC Responses

Trends Microbiol. 2018 Apr;26(4):253-265. doi: 10.1016/j.tim.2017.10.007. Epub 2017 Nov 20.

Abstract

HIV-1 envelope glycoproteins (Env) represent the only virus-specific antigen exposed at the surface of infected cells. In its unliganded form, Env from primary viruses samples a 'closed' conformation (State 1), which is preferentially recognized by broadly neutralizing antibodies (bNAbs). CD4 engagement drives Env into an intermediate 'partially open' (State 2) and then into the 'open' CD4-bound conformation (State 3). Emerging evidence suggests a link between Env conformation and Ab-dependent cellular cytotoxicity (ADCC). HIV-1-infected cells exposing Env in the CD4-bound conformation are susceptible to ADCC mediated by CD4-induced Abs and HIV+sera. Cells exposing State 1 Env are susceptible to ADCC mediated by bNAbs. Here, we discuss how Env conformation affects ADCC responses and in vitro measurements.

Keywords: ADCC; CD4; HIV-1; Nef; Vpu; envelope glycoproteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Neutralizing
  • Antibody-Dependent Cell Cytotoxicity / physiology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Epitopes, T-Lymphocyte / immunology
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • HIV-1 / metabolism*
  • HIV-1 / pathogenicity
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Protein Conformation
  • Viral Regulatory and Accessory Proteins
  • env Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • Antibodies, Neutralizing
  • Epitopes, T-Lymphocyte
  • Human Immunodeficiency Virus Proteins
  • KLRK1 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Viral Regulatory and Accessory Proteins
  • env Gene Products, Human Immunodeficiency Virus
  • vpu protein, Human immunodeficiency virus 1

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