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- W2037334416 endingPage "2761" @default.
- W2037334416 startingPage "2752" @default.
- W2037334416 abstract "Abstract 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 α and β 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-α 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- α/β 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." @default.
- W2037334416 created "2016-06-24" @default.
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- W2037334416 creator A5090289772 @default.
- W2037334416 date "2001-11-01" @default.
- W2037334416 modified "2023-10-12" @default.
- W2037334416 title "HIV-1 Nef activates STAT1 in human monocytes/macrophages through the release of soluble factors" @default.
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- W2037334416 doi "https://doi.org/10.1182/blood.v98.9.2752" @default.
- W2037334416 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11675348" @default.
- W2037334416 hasPublicationYear "2001" @default.
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