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Molecular and Cellular Biology, May 1999, p. 3607-3613, Vol. 19, No. 5
Department of Medical Microbiology and
Immunology, University of Wisconsin
Received 17 December 1998/Returned for modification 21 January
1999/Accepted 2 February 1999
Cells respond to contact with human cytomegalovirus (HCMV) virions
by initiating intracellular signaling and gene expression characteristic of the interferon (IFN)-responsive pathway. Herein, we
demonstrate that a principal mechanism of HCMV-induced signal transduction is via an interaction of the primary viral ligand, glycoprotein B (gB), with its cellular receptor. Cells incubated with a
purified, soluble form of gB resulted in the transcriptional upregulation of IFN-responsive genes OAS and ISG54 (encoding 2'-5' oligoadenylate synthetase and an IFN-stimulated gene product of 54 kDa)
to a comparable level as virions or IFN. Gene induction was an
immediate and direct response to gB which did not require de novo
protein synthesis. Neither the initial virus attachment site, heparan
sulfate proteoglycans, nor the IFN-
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Engagement of the Cellular Receptor for
Glycoprotein B of Human Cytomegalovirus Activates the
Interferon-Responsive Pathway
Madison, Madison, Wisconsin
53706-1532
/
or IFN-
receptors are
involved in the response. Pleotropic protein phosphorylation was
required for cellular gene induction, and the mitogen-activated protein
kinases ERK1 and ERK2 were activated in response to the ligand.
Together these data indicate that a principal means by which
cytomegalovirus induces intracellular signaling and activation of the
interferon-responsive pathway is via an interaction of gB with an as
yet unidentified, likely novel cellular receptor that interfaces with
the IFN signaling pathway.
*
Corresponding author. Mailing address: Department of
Medical Microbiology and Immunology, 1300 University Ave., MS493,
University of Wisconsin
Madison Medical School, Madison, WI
53706-1532. Phone: (608) 262-1474. Fax: (608) 262-8418. E-mail:
tcompton{at}facstaff.wisc.edu.
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