The viral protein Nef is a virulence factor that plays multiple roles during the HIV replication cycle. Nef expression regulates cell surface expression of critical proteins, inducing downregulation of CD4 and MIC-I, T cell receptor signaling and apoptosis, inducing pro-apoptotic effects in uninfected bystander cells and anti-apoptotic effects in infected cells [1]. The exogenous Nef treatment of cells in culture has several effects ranging from induction of apoptosis in uninfected T cells, maturation in dendritic cells and suppression of CD40-dependent immunoglobulin class switching in B cells. We have previously observed that Nef treatment of monocyte-derived macrophages (MDM) induces a pro-inflammatory state characterized by the activation of NF-KB pathway and the release of a set of chemo- and cytokines. Analyses performed on treated MDM showed that Nef is able to up-regulate the expression of IFN beta mRNA. The induction of IFN beta mRNA is correlated to the phosphorylation of IRF-3 and is followed by the synthesis and the release of this cytokine leading to the activation of STAT2 and the induction of IRF-7.

In vitro treatment of human monocyte-derived macrophages with HIV-1 protein nef activates cellular signaling pathways leading to type IIFN production

MANGINO, GIORGIO;ROMEO, Giovanna;
2006

Abstract

The viral protein Nef is a virulence factor that plays multiple roles during the HIV replication cycle. Nef expression regulates cell surface expression of critical proteins, inducing downregulation of CD4 and MIC-I, T cell receptor signaling and apoptosis, inducing pro-apoptotic effects in uninfected bystander cells and anti-apoptotic effects in infected cells [1]. The exogenous Nef treatment of cells in culture has several effects ranging from induction of apoptosis in uninfected T cells, maturation in dendritic cells and suppression of CD40-dependent immunoglobulin class switching in B cells. We have previously observed that Nef treatment of monocyte-derived macrophages (MDM) induces a pro-inflammatory state characterized by the activation of NF-KB pathway and the release of a set of chemo- and cytokines. Analyses performed on treated MDM showed that Nef is able to up-regulate the expression of IFN beta mRNA. The induction of IFN beta mRNA is correlated to the phosphorylation of IRF-3 and is followed by the synthesis and the release of this cytokine leading to the activation of STAT2 and the induction of IRF-7.
88-7587-278-3
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/690897
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