The human cytomegalovirus-encoded chemokine receptor US28 induces caspase-dependent apoptosis.

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Serval ID
serval:BIB_CCBF6F5B954D
Type
Article: article from journal or magazin.
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Publications
Institution
Title
The human cytomegalovirus-encoded chemokine receptor US28 induces caspase-dependent apoptosis.
Journal
FEBS Journal
Author(s)
Pleskoff O., Casarosa P., Verneuil L., Ainoun F., Beisser P., Smit M., Leurs R., Schneider P., Michelson S., Ameisen J.C.
ISSN
1742-464X (Print)
ISSN-L
1742-464X
Publication state
Published
Issued date
2005
Volume
272
Number
16
Pages
4163-4177
Language
english
Abstract
Viral subversion of apoptosis regulation plays an important role in the outcome of host/virus interactions. Although human cytomegalovirus (HCMV) encodes several immediate early (IE) antiapoptotic proteins (IE1, IE2, vMIA and vICA), no proapoptotic HCMV protein has yet been identified. Here we show that US28, a functional IE HCMV-encoded chemokine receptor, which may be involved in both viral dissemination and immune evasion, constitutively induces apoptosis in several cell types. In contrast, none of nine human cellular chemokine receptors, belonging to three different subfamilies, induced any significant level of apoptosis. US28-induced cell death involves caspase 10 and caspase 8 activation, but does not depend on the engagement of cell-surface death receptors of the tumour necrosis factor receptor/CD95 family. US28 cell-death induction is prevented by coexpression of C-FLIP, a protein that inhibits Fas-associated death domain protein (FADD)-mediated activation of caspase 10 and caspase 8, and by coexpression of the HCMV antiapoptotic protein IE1. The use of US28 mutants indicated that the DRY sequence of its third transmenbrane domain, required for constitutive G-protein signalling, and the US28 intracellular terminal domain required for constitutive US28 endocytosis, are each partially required for cell-death induction. Thus, in HCMV-infected cells, US28 may function either as a chemokine receptor, a phospholipase C activator, or a proapoptotic factor, depending on expression levels of HCMV and/or cellular antiapoptotic proteins.
Keywords
Apoptosis/physiology, CASP8 and FADD-Like Apoptosis Regulating Protein, Caspases/metabolism, Cell Line, Enzyme Activation, Humans, Immediate-Early Proteins/physiology, Intracellular Signaling Peptides and Proteins/physiology, Receptors, Chemokine/physiology, Viral Proteins/physiology
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 17:30
Last modification date
20/08/2019 15:47
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