Linked Life Data

11675348

Source:http://linkedlifedata.com/resource/pubmed/id/11675348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-10-24
pubmed:abstractText
Monocytes/macrophages play a predominant role in the immunologic network by secreting and reacting to a wide range of soluble factors. Human immunodeficiency virus (HIV) infection leads to deep immunologic dysfunctions, also as a consequence of alterations in the pattern of cytokine release. Recent studies on in vivo models demonstrated that the expression of HIV Nef alone mimics many pathogenetic effects of HIV infection. In particular, Nef expression in monocytes/macrophages has been correlated with remarkable modifications in the pattern of secreted soluble factors, suggesting that the interaction of Nef with monocytes/macrophages plays a role in the pathogenesis of acquired immunodeficiency syndrome (AIDS). This study sought to define possible alterations in intracellular signaling induced by Nef in monocytes/macrophages. Results demonstrate that HIV-1 Nef specifically activates both alpha and beta isoforms of the signal transducer and activator of transcription 1 (STAT1). This was observed both by infecting human monocyte-derived macrophages (MDMs) with HIV-1 deletion mutants, and by exploiting the ability of MDMs to internalize soluble, recombinant Nef protein (rNef). STAT1-alpha activation occurs on phosphorylation of both C-terminal Tyr701 and Ser727 and leads to a strong binding activity. Nef-dependent STAT1 activation is followed by increased expression of both STAT1 and interferon regulatory factor-1, a transcription factor transcriptionally regulated by STAT1 activation. It was also established that Nef-induced STAT1- alpha/beta activation occurs through the secretion of soluble factors. Taken together, the results indicate that HIV-1 Nef could interfere with STAT1-governed intracellular signaling in human monocytes/macrophages.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2752-61
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11675348-Acquired Immunodeficiency Syndrome, pubmed-meshheading:11675348-Adult, pubmed-meshheading:11675348-Cytokines, pubmed-meshheading:11675348-DNA-Binding Proteins, pubmed-meshheading:11675348-Gene Products, nef, pubmed-meshheading:11675348-HIV-1, pubmed-meshheading:11675348-Humans, pubmed-meshheading:11675348-Interferon Regulatory Factor-1, pubmed-meshheading:11675348-Macrophages, pubmed-meshheading:11675348-Male, pubmed-meshheading:11675348-Monocytes, pubmed-meshheading:11675348-Phosphoproteins, pubmed-meshheading:11675348-Phosphorylation, pubmed-meshheading:11675348-Protein Binding, pubmed-meshheading:11675348-Protein Isoforms, pubmed-meshheading:11675348-STAT1 Transcription Factor, pubmed-meshheading:11675348-Sequence Deletion, pubmed-meshheading:11675348-Signal Transduction, pubmed-meshheading:11675348-Trans-Activators, pubmed-meshheading:11675348-nef Gene Products, Human Immunodeficiency Virus
pubmed:year
2001
pubmed:articleTitle
HIV-1 Nef activates STAT1 in human monocytes/macrophages through the release of soluble factors.
pubmed:affiliation
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy. federico@iss.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't