Interaction of glycoprotein H of human herpesvirus 6 with the cellular receptor CD46.
Human herpesvirus 6 (HHV-6) employs the complement regulator CD46 (membrane cofactor protein) as a receptor for fusion and entry into target cells. Like other known herpesviruses, HHV-6 encodes multiple glycoproteins, several of which have been implicated in the entry process. In this report, we present evidence that glycoprotein H (gH) is the viral component responsible for binding to CD46. Antibodies to CD46 co-immunoprecipitated an approximately 110-kDa protein band specifically associated with HHV-6-infected cells. This protein was identified as gH by selective depletion with an anti-gH monoclonal antibody, as well as by immunoblot analysis with a rabbit hyperimmune serum directed against a gH synthetic peptide. In reciprocal experiments, a monoclonal antibody against HHV-6 gH was found to co-immunoprecipitate CD46. Studies using monoclonal antibodies directed against specific CD46 domains, as well as engineered constructs lacking defined CD46 regions, demonstrated a close correspondence between the CD46 domains involved in the interaction with gH and those previously shown to be critical for HHV-6 fusion (i.e. short consensus repeats 2 and 3).
Laboratory of Viral Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
Fabio
F
Santoro
Heather L
HL
Greenstone
Alessandra
A
Insinga
M Kathryn
MK
Liszewski
John P
JP
Atkinson
Paolo
P
Lusso
Edward A
EA
Berger
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014162:Transfection; D014759:Viral Envelope Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010455:Peptides; D014759:Viral Envelope Proteins; C070917:glycoprotein H, herpesvirus 6