Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-8-9
pubmed:abstractText
Latency-associated nuclear antigen 1 (LANA-1) of Kaposi's sarcoma-associated herpesvirus (KSHV) is the major viral latent protein and functions as a multifaceted protein. Here, we report that LANA-1 attenuates the endothelial response to tumor necrosis factor alpha (TNF-?) stimulation and inhibits consequent neutrophil chemotaxis. Reporter assays showed that LANA-1 constantly repressed nuclear factor (NF)-?B transactivity upon TNF-? stimulation. We also found that LANA-1 decreased nuclear p65 protein levels through enhancement of polyubiquitylation-mediated p65 degradation and that an elongin B/elongin C-cullin 5-LANA-1-p65 complex assembled by LANA-1 was responsible for this enhanced p65 degradation. In telomerase-immortalized human umbilical vein endothelial cells, LANA-1 was demonstrated to repress interleukin-8 expression, which was involved in neutrophil recruitment to the inflammatory site. Through an in vitro transmigration assay, we determined a suppressive effect of LANA-1 on neutrophil chemotaxis. Our work suggests that KSHV LANA-1 is a negative modulator of acute inflammation and sheds light on a new mechanism by which KSHV during the latent life cycle evades the host innate immune response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8606-15
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen reduces interleukin-8 expression in endothelial cells and impairs neutrophil chemotaxis by degrading nuclear p65.
pubmed:affiliation
Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai 200025, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't