Functions of the unique N-terminal region of glycoprotein E in the pathogenesis of varicella-zoster virus infection

Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):282-7. doi: 10.1073/pnas.0912373107. Epub 2009 Dec 4.


Varicella-zoster virus (VZV) is an alphaherpesvirus that infects skin, lymphocytes, and sensory ganglia. VZV glycoprotein E (gE) has a unique N-terminal region (aa1-188), which is required for replication and includes domains involved in secondary envelopment, efficient cell-cell spread, and skin infection in vivo. The nonconserved N-terminal region also mediates binding to the insulin-degrading enzyme (IDE), which is proposed to be a VZV receptor. Using viral mutagenesis to make the recombinant rOka-DeltaP27-G90, we showed that amino acids in this region are required for gE/IDE binding in infected cells; this deletion reduced cell-cell spread in vitro and skin infection in vivo. However, a gE point mutation, linker insertions, and partial deletions in the aa27-90 region, and deletion of a large portion of the unique N-terminal region, aa52-187, had similar or more severe effects on VZV replication in vitro and in vivo without disrupting the gE/IDE interaction. VZV replication in T cells in vivo was not impaired by deletion of gE aa27-90, suggesting that these gE residues are not essential for VZV T cell tropism. However, the rOka-DeltaY51-P187 mutant failed to replicate in T cell xenografts as well as skin in vivo. VZV tropism for T cells and skin, which is necessary for its life cycle in the human host, requires this nonconserved region of the N-terminal region of VZV gE.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chickenpox / metabolism
  • Chickenpox / physiopathology*
  • Herpesvirus 3, Human / genetics
  • Herpesvirus 3, Human / pathogenicity*
  • Herpesvirus 3, Human / physiology
  • Humans
  • Mice
  • Mice, SCID
  • Mutagenesis
  • Protein Structure, Tertiary
  • Skin / cytology
  • Skin / pathology
  • Skin / virology
  • Skin Diseases / pathology
  • Skin Diseases / virology
  • Skin Transplantation
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Transplantation, Heterologous
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virus Replication / genetics


  • Viral Envelope Proteins
  • glycoprotein E, varicella-zoster virus