N- and C-terminal external domains of human herpesvirus-6 glycoprotein H affect a fusion-associated conformation mediated by glycoprotein L binding the N terminus

J Gen Virol. 1999 Jun;80 ( Pt 6):1485-1494. doi: 10.1099/0022-1317-80-6-1485.

Abstract

Human herpesvirus-6 (HHV-6), like other betaherpesviruses, shows cell fusion with wild-type strains, and this cellular spread is mediated by the glycoprotein gH/gL complex. Anti-fusion monoclonal antibodies (MAbs) specific for HHV-6 glycoprotein gH inhibit infection and prevent cellular spread by syncytia formation. Reactivity of these MAbs with gH deletion mutants suggests a conserved C-terminal fusion-associated domain. A conserved motif here has an N-glycosylation site and characteristics of a beta turn. Motif deletion abrogated MAb recognition while co-expression with glycoprotein gL restored this conformational epitope, indicating the importance of folding and not glycosylation at this site. Our previous studies showed gL binding to gH at an N-terminal domain specific for betaherpesviruses. To further examine the function of this N-terminal domain, a betaherpesvirus-specific motif was deleted. This mutant gH still bound gL, and was recognized by the anti-fusion MAbs; however, recognition was now primarily in the immature form and reduced during processing to the mature form. A model is discussed whereby gL binding gH at the N-terminal domain acts to draw together the C-terminal extracellular domain and this interaction affects a functional conformation during glycoprotein maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Chlorocebus aethiops
  • Epitopes / immunology
  • Herpesvirus 6, Human / chemistry
  • Herpesvirus 6, Human / genetics
  • Herpesvirus 6, Human / metabolism*
  • Herpesvirus 6, Human / pathogenicity
  • Humans
  • Membrane Fusion / physiology*
  • Mutagenesis, Site-Directed
  • Plasmids
  • Precipitin Tests
  • Protein Conformation
  • Structure-Activity Relationship
  • Vero Cells
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*

Substances

  • Antibodies, Monoclonal
  • Epitopes
  • Viral Envelope Proteins
  • glycoprotein H, herpesvirus 6