UL74 of human cytomegalovirus reduces the inhibitory effect of gH-specific and gB-specific antibodies

Arch Virol. 2011 Dec;156(12):2145-55. doi: 10.1007/s00705-011-1105-x. Epub 2011 Sep 22.

Abstract

The human cytomegalovirus (HCMV) glycoproteins gH (UL75) and gL (UL115) can form complexes with gO (UL74) or with proteins of the UL128-UL131A locus. Deletion of gO abolishes cell-free virus transmission and renders cell-associated virus transmission in fibroblasts more sensitive to inhibition by human anti-HCMV serum. To test whether the latter effect is specific for gO, we compared mutants with deletions in UL74, UL99 and the UL128-131A locus regarding their sensitivity to anti-HCMV antibodies. UL74 deletion mutants were more sensitive to a further restriction by polyspecific or gH-specific antibodies than control mutants, showing that gO specifically protects focal growth against inhibitory antibodies. This effect was not confined to gH-specific antibodies, as UL74 deletion mutants were also inhibited by an anti-gB antibody. In conclusion, gO specifically promotes focal spread in the presence of gH and gB antibodies, thus contributing to the ability of HCMV to resist the host's immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • Antibody Specificity
  • Base Sequence
  • Cells, Cultured
  • Chromosomes, Artificial, Bacterial / genetics
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus / ultrastructure
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / virology
  • DNA, Viral / genetics
  • Fibroblasts / virology
  • Genes, Viral
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Mutation
  • Sequence Deletion
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Virulence / genetics
  • Virulence / immunology

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Membrane Glycoproteins
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus
  • glycoprotein H, Cytomegalovirus
  • glycoprotein O, cytomegalovirus