Journal of General Virology, Vol 80, 1485-1494, Copyright © 1999 by Society for General Microbiology

ARTICLES

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

RA Anderson and UA Gompels
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, University of London, Keppel Street, London WC1E 7HT, UK

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.

This article has been cited by other articles:

				S. M. Pedersen, B. Oster, B. Bundgaard, and P. Hollsberg Induction of Cell-Cell Fusion from Without by Human Herpesvirus 6B J. Virol., October 1, 2006; 80(19): 9916 - 9920. [Abstract] [Full Text] [PDF]

				L. Wu, C. M. Borza, and L. M. Hutt-Fletcher Mutations of Epstein-Barr Virus gH That Are Differentially Able To Support Fusion with B Cells or Epithelial Cells J. Virol., September 1, 2005; 79(17): 10923 - 10930. [Abstract] [Full Text] [PDF]

				F. Santoro, H. L. Greenstone, A. Insinga, M. K. Liszewski, J. P. Atkinson, P. Lusso, and E. A. Berger Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46 J. Biol. Chem., July 3, 2003; 278(28): 25964 - 25969. [Abstract] [Full Text] [PDF]

				Y. Mori, X. Yang, P. Akkapaiboon, T. Okuno, and K. Yamanishi Human Herpesvirus 6 Variant A Glycoprotein H-Glycoprotein L-Glycoprotein Q Complex Associates with Human CD46 J. Virol., April 15, 2003; 77(8): 4992 - 4999. [Abstract] [Full Text] [PDF]

				Y. Mori, T. Seya, H. L. Huang, P. Akkapaiboon, P. Dhepakson, and K. Yamanishi Human Herpesvirus 6 Variant A but Not Variant B Induces Fusion from Without in a Variety of Human Cells through a Human Herpesvirus 6 Entry Receptor, CD46 J. Virol., June 5, 2002; 76(13): 6750 - 6761. [Abstract] [Full Text] [PDF]