CMV-encoded Fcγ receptors: modulators at the interface of innate and adaptive immunity

Semin Immunopathol. 2014 Nov;36(6):627-40. doi: 10.1007/s00281-014-0448-2. Epub 2014 Oct 7.

Abstract

The constant region of IgG antibodies mediates antiviral activities upon engaging host Fcγ receptors (FcγRs) expressed by a variety of immune cells, such as antibody-dependent cellullar cytotoxcity (ADCC) executed by natural killer (NK)cells. Human cytomegalovirus (HCMV) is unique among viruses by encoding also an array of several Fcγ-binding glycoproteins with cell surface disposition and concomitant incorporation into the virion. Evidence is increasing that the virus-encoded Fcγ receptors differ in their Fcγ binding mode but effectively operate as adversaries of host FcγRs since they are able to prevent IgG-mediated triggering of activating host FcγRs, i.e., FcγRI, FcγRIIA, and FcγRIIIA. Here we discuss virus-encoded FcγRs as the first known HCMV inhibitors of IgG-mediated immunity which could account for the limited efficacy of HCMV hyperimmune globulin in clinical settings. A better understanding of their molecular mode of action opens up new perspectives for improving IgG therapies against HCMV disease.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antibodies, Viral / immunology
  • Carrier Proteins / metabolism
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / genetics
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / therapy
  • Humans
  • Immunity, Innate
  • Immunoglobulin G / immunology
  • Immunomodulation
  • Immunotherapy
  • Ligands
  • Protein Binding
  • Receptors, IgG / chemistry
  • Receptors, IgG / genetics*
  • Receptors, IgG / metabolism
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • Antibodies, Viral
  • Carrier Proteins
  • Immunoglobulin G
  • Ligands
  • Receptors, IgG
  • Viral Proteins