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Originally published In Press as doi:10.1074/jbc.M302373200 on April 29, 2003
J. Biol. Chem., Vol. 278, Issue 28, 25964-25969, July 11, 2003
Interaction of Glycoprotein H of Human Herpesvirus 6 with the Cellular Receptor CD46*
Fabio Santoro ,
Heather L. Greenstone ,
Alessandra Insinga ,
M. Kathryn Liszewski ¶,
John P. Atkinson ¶,
Paolo Lusso || and
Edward A. Berger **
From the
Laboratory of Viral Diseases, NIAID,
National Institutes of Health, Bethesda, Maryland 20892, the
Unit of Human Virology, Department of Biological
and Technical Research, San Raffaele Scientific Institute, 20132 Milano,
Italy, the ¶Division of Rheumatology, Department
of Medicine, Washington University School of Medicine, St. Louis, Missouri
63110 and the ||Department of Medical Sciences,
University of Cagliari Medical School, 09100 Cagliari, Italy
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 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).
Received for publication, March 7, 2003
, and in revised form, April 29, 2003.
* This work was supported in part by Grants 50C17 and 50D17 from the Third
and Fourth AIDS Projects, Instituto Superiore di Sanit (National Institute of
Health), Rome and by National Institutes of Health Grant R01 AI37618. The
costs of publication of this article were defrayed in part by the payment of
page charges. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section 1734
solely to indicate this fact.
**
To whom correspondence should be addressed: Bldg. 4, Rm. 237, National
Institutes of Health, Bethesda, MD 20892. Tel.: 301-402-2481; Fax:
301-480-1147; E-mail:
edward_berger{at}nih.gov.

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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
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