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PMID: 10207084 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Engagement of the cellular receptor for glycoprotein B of human cytomegalovirus activates the interferon-responsive pathway.

Molecular and cellular biology ·Vol. 19 ·No. 5 ·1999-05-00 ·Pages 3607-13

Boyle KA, Pietropaolo RL, Compton T

Abstract

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-alpha/beta or IFN-gamma 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.

MeSH Terms
2',5'-Oligoadenylate Synthetase/genetics Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Gene Expression Regulation/genetics Heparitin Sulfate/metabolism Humans Interferons/metabolism Phosphorylation Protein Denaturation RNA, Messenger/metabolism Receptors, Cell Surface/metabolism Signal Transduction/physiology Transcriptional Activation Up-Regulation/genetics Viral Envelope Proteins/metabolism Viral Proteins/metabolism
Chemicals
RNA, Messenger Receptors, Cell Surface Viral Envelope Proteins Viral Proteins glycoprotein B, Simplexvirus Interferons Heparitin Sulfate Calcium-Calmodulin-Dependent Protein Kinases 2',5'-Oligoadenylate Synthetase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Boyle K A
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin 53706-1532, USA.
Pietropaolo R L
Compton T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.5.3607
Published
1999-05-00
Pages
3607-13
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84158
Subset
IM
Grants
NIAID NIH HHS · R01 AI034998 · United States
NIAID NIH HHS · R01 AI-34998 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.5.3607 PMC Full Text View journal details
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