Engagement of the cellular receptor for glycoprotein B of human cytomegalovirus activates the interferon-responsive pathway. Mol Cell Biol 1999 May;19(5):3607-13
Date
04/17/1999Pubmed ID
10207084Pubmed Central ID
PMC84158DOI
10.1128/MCB.19.5.3607Scopus ID
2-s2.0-0032931994 (requires institutional sign-in at Scopus site) 178 CitationsAbstract
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.
Author List
Boyle KA, Pietropaolo RL, Compton TMESH terms used to index this publication - Major topics in bold
2',5'-Oligoadenylate SynthetaseCalcium-Calmodulin-Dependent Protein Kinases
Cell Line
Gene Expression Regulation
Heparitin Sulfate
Humans
Interferons
Phosphorylation
Protein Denaturation
RNA, Messenger
Receptors, Cell Surface
Signal Transduction
Transcriptional Activation
Up-Regulation
Viral Envelope Proteins
Viral Proteins
