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.
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.
Anderson
R A
RA
Gompels
U A
UA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010957:Plasmids; D011233:Precipitin Tests; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D014759:Viral Envelope Proteins; C070917:glycoprotein H, herpesvirus 6