Linked Life Data

21248029

Source:http://linkedlifedata.com/resource/pubmed/id/21248029

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-3-16
pubmed:abstractText
Dendritic cells are sentinels in innate and adaptive immunity. Upon virus infection, a complex program is in operation, which activates I?B kinase (IKK), a key regulator of inflammatory cytokines and costimulatory molecules. Here we show that the ?(1)34.5 protein, a virulence factor of herpes simplex viruses, blocks Toll-like receptor-mediated dendritic cell maturation. While the wild-type virus inhibits the induction of major histocompatibility complex (MHC) class II, CD86, interleukin-6 (IL-6), and IL-12, the ?(1)34.5-null mutant does not. Notably, ?(1)34.5 works in the absence of any other viral proteins. When expressed in mammalian cells, including dendritic cells, ?(1)34.5 associates with IKK?/? and inhibits NF-?B activation. This is mirrored by the inhibition of IKK?/? phosphorylation, p65/RelA phosphorylation, and nuclear translocation in response to lipopolysaccharide or poly(I:C) stimulation. Importantly, ?(1)34.5 recruits both IKK?/? and protein phosphatase 1, forming a complex that dephosphorylates two serine residues within the catalytic domains of I?B kinase. The amino-terminal domain of ?(1)34.5 interacts with IKK?/?, whereas the carboxyl-terminal domain binds to protein phosphatase 1. Deletions or mutations in either domain abolish the activity of ?(1)34.5. These results suggest that the control of I?B kinase dephosphorylation by ?(1)34.5 represents a critical viral mechanism to disrupt dendritic cell functions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3397-407
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A herpesvirus virulence factor inhibits dendritic cell maturation through protein phosphatase 1 and Ikappa B kinase.
pubmed:affiliation
Department of Microbiology and Immunology (M/C 790), College of Medicine, University of Illinois, Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural