Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-3-13
pubmed:abstractText
Herpes simplex viruses (HSVs) are able to hijack the host-cell IkappaB kinase (IKK)/NF-kappaB pathway, which regulates critical cell functions from apoptosis to inflammatory responses; however, the molecular mechanisms involved and the outcome of the signaling dysregulation on the host-virus interaction are mostly unknown. Here we show that in human keratinocytes HSV-1 attains a sophisticated control of the IKK/NF-kappaB pathway, inducing two distinct temporally controlled waves of IKK activity and disrupting the NF-kappaB autoregulatory mechanism. Using chromatin immunoprecipitation we demonstrate that dysregulation of the NF-kappaB-response is mediated by a virus-induced block of NF-kappaB recruitment to the promoter of the IkappaBalpha gene, encoding the main NF-kappaB-inhibitor. We also show that HSV-1 redirects NF-kappaB recruitment to the promoter of ICP0, an immediate-early viral gene with a key role in promoting virus replication. The results reveal a new level of control of cellular functions by invading viruses and suggest that persistent NF-kappaB activation in HSV-1-infected cells, rather than being a host response to the virus, may play a positive role in promoting efficient viral replication.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7110-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16407234-Blotting, Western, pubmed-meshheading:16407234-Cell Line, pubmed-meshheading:16407234-Chromatin Immunoprecipitation, pubmed-meshheading:16407234-DNA Primers, pubmed-meshheading:16407234-Gene Expression Regulation, pubmed-meshheading:16407234-Genes, Viral, pubmed-meshheading:16407234-Herpesvirus 1, Human, pubmed-meshheading:16407234-Humans, pubmed-meshheading:16407234-I-kappa B Proteins, pubmed-meshheading:16407234-Immediate-Early Proteins, pubmed-meshheading:16407234-Inflammation, pubmed-meshheading:16407234-Keratinocytes, pubmed-meshheading:16407234-Models, Genetic, pubmed-meshheading:16407234-NF-kappa B, pubmed-meshheading:16407234-Plasmids, pubmed-meshheading:16407234-Promoter Regions, Genetic, pubmed-meshheading:16407234-Prostaglandins A, pubmed-meshheading:16407234-RNA, Messenger, pubmed-meshheading:16407234-Signal Transduction, pubmed-meshheading:16407234-Simplexvirus, pubmed-meshheading:16407234-Time Factors, pubmed-meshheading:16407234-Transcription, Genetic, pubmed-meshheading:16407234-Transfection, pubmed-meshheading:16407234-Ubiquitin-Protein Ligases, pubmed-meshheading:16407234-Ultraviolet Rays
pubmed:year
2006
pubmed:articleTitle
Herpes simplex virus disrupts NF-kappaB regulation by blocking its recruitment on the IkappaBalpha promoter and directing the factor on viral genes.
pubmed:affiliation
Department of Biology and Dermatology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't