The Human Immunodeficiency Virus Type 1 Vpu Protein Inhibits NF-κB Activation by Interfering with βTrCP-mediated Degradation of IκB

Bour, Stephan; Perrin, Christèle; Akari, Hirofumi; Strebel, Klaus

doi:10.1074/jbc.m010533200

Cited by 165 publications

(194 citation statements)

References 63 publications

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“…Conversely, the function of bTrCP/HOS can be readily inhibited by expression of a pseudo-substrate (Vpu; Bour et al, 2001) or the substrate-mimicking phosphopeptides (Yaron et al, 1997) or dominant negative constructs lacking F-box (Fuchs et al, 1999;Hart et al, 1999;Kitagawa et al, 1999;Kroll et al, 1999;Latres et al, 1999;Spencer et al, 1999;Suzuki et al, 1999;Winston et al, 1999b;Yaron et al, 1998). These observations suggest that regulation of bTrCP and HOS levels will contribute to the outcome of Wnt/b-catenin/Tcf and NF-kB signaling pathways.…”

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confidence: 87%

Inhibition of HOS expression and activities by Wnt pathway

Spiegelman

Tang

Katoh³

et al. 2002

Oncogene

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bTrCP and HOS are closely related F-box proteins, which play key roles in ubiquitination and degradation of b-catenin and IkB through associating with those phosphorylated substrates and recruiting SCF E3 ubiquitin ligase. Here we report that activation of Wnt/b-catenin signal transduction pathway elevates bTrCP levels but inhibits expression of HOS in 293T cells. Similar disparity is likely to exist in human colorectal tumors. In the NIH3T3 cells, which express HOS, but not bTrCP, Wnt/b-catenin signaling leads to inhibition of HOS promoter activity and NF-kB-driven transcription as well as to stabilization of b-catenin. These results indicate that expression and activities of HOS are negatively regulated by Wnt/b-catenin pathway.

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mentioning

confidence: 87%

Inhibition of HOS expression and activities by Wnt pathway

Spiegelman

Tang

Katoh³

et al. 2002

Oncogene

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“…In contrast, the present results suggest that HLA-G1 molecules may be degraded before their transport to the membrane, reducing HLA-G1 expression at the cell surface. Indeed, Vpu interacts with various molecules within the endoplasmic reticulum, including CD4, and alters their transport to the membrane by directing them to the degradation pathway (Lenburg & Landau, 1993;Bour et al, 2001). In the case of Vpu-mediated CD4 degradation, Vpu interacts with a discrete amino acid sequence in the cytoplasmic tail of CD4 containing a dilysine motif (EKKT) (Lenburg & Landau, 1993;Bour et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1

Derrien

Pizzato

Dolcini

et al. 2004

Journal of General Virology

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Human immunodeficiency virus 1 (HIV-1) downregulates cell surface expression of HLA-A and HLA-B but not HLA-C or HLA-E to ultimately escape immune defences. Here, it is shown that cell surface expression of the non-classical HLA-G1 is also downregulated by HIV-1, by using co-transfection experiments and infection with cell-free HIV-1 of HLA-G1-expressing U87 glioma cells or macrophages in primary culture. Moreover, co-transfection experiments using proviruses deleted in either nef or vpu or plasmids encoding HIV-1 Nef and Vpu mixed together with a HLA-G1-expressing construct demonstrated that HLA-G1 downregulation is Nef-independent and Vpu-dependent, contrasting with the Nef-and Vpu-dependent HLA-A2 downregulation. Together, these results show that the decrease of HLA-A2 and HLA-G1 caused by HIV-1 occurs through distinct mechanisms. INTRODUCTIONExpression of major histocompatibility class I (MHC-I) molecules is required to initiate and sustain an efficient anti-viral immunity (Tortorella et al., 2000). Human immunodeficiency virus 1 (HIV-1) has evolved multiple immunoevasive strategies to escape the host immune response (Collins & Baltimore, 1999). This includes downregulation of cell surface MHC-I, which could induce the decline of HIV-specific CD8 + T cells and modulation of the function of natural killer cells (Collins & Baltimore, 1999). MHC-I downregulation was shown to be dependent on HIV Nef mainly, affecting endocytosis of classical HLA-A and HLA-B, but not that of HLA-C or of non-classical HLA-E (Cohen et al., 1999;Blagoveshchenskaya et al., 2002). Unlike other MHC-I molecules, HLA-G is characterized by a low polymorphism and a restricted tissue distribution, being found mostly in placental trophoblasts, thymic epithelial cells (Le Bouteiller & Blaschitz, 1999) and macrophages (Mw) (Yang et al., 1996). Moreover, HLA-G is transcribed and translated into multiple membrane-bound and soluble isoforms, as a result of alternative splicing (Ishitani & Geraghty, 1992). The soluble HLA-G1 isoform was shown to induce apoptosis of activated CD8 + T cells (Fournel et al., 2000) and to suppress the allo-proliferative response of CD4 + T cells (Lila et al., 2001). Recent studies suggest that, in pathological conditions, HLA-G1 expression could be either induced in cells that do not usually express this MHC-I, such as in certain tumours (Lefebvre et al., 2002;Wiendl et al., 2002), or upregulated in monocytes/Mw during the chronic phase of viral infections (Onno et al., 2000;Lozano et al., 2002). In addition, HLA-G1 has the ability to present viral peptides to cytotoxic CD8 + T cells (Lenfant et al., 2003), suggesting that this class Ib molecule could also play a role during early phases of viral infections.In this report, we asked whether acute HIV-1 infection could modulate cell surface expression of HLA-G1. We found that HIV-1 decreases cell surface expression of HLA-G1 through a Nef-independent and Vpu-dependent mechanism, whereas both proteins affect HLA-A2 expression. METHODSCells and cell lines. A U87 cell lin...

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“…HIV-1 tat may down-regulate mannose receptor transcription (Caldwell et al, 2000). HIV-1 vpu impedes NF-B activation by inhibiting I-B degradation (Bour et al, 2001) in T-cell lines. HIV-1 nef may alter ASK1 signal transduction pathways (Geleziunas et al, 2001) and down-regulate NF-B signaling in T-cell lines (Bandres and Ratner, 1994), reduce mannose receptor surface expression on dendritic cells (Quaranta et al, 2002), and down-modulate Fc␥-R expression on monocyte-derived macrophages (De et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

Zhang

Zhu

et al. 2005

MBoC

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Human alveolar macrophages (AMs) phagocytose Pneumocystis (Pc) organisms predominantly through mannose receptors, although the molecular mechanism mediating this opsonin-independent process is not known. In this study, using AMs from healthy individuals, Pc phagocytosis was associated with focal F-actin polymerization and Cdc42, Rac1, and Rho activation in a time-dependent manner. Phagocytosis was primarily dependent on Cdc42 and RhoB activation (as determined by AM transfection with Cdc42 and RhoB dominant-negative alleles) and mediated predominantly through mannose receptors (as determined by siRNA gene silencing of AM mannose receptors). Pc also promoted PAK-1 phosphorylation, which was also dependent on RhoGTPase activation. HIV infection of AMs (as a model for reduced mannose receptor expression and function) was associated with impaired F-actin polymerization, reduced Cdc42 and Rho activation, and markedly reduced PAK-1 phosphorylation in response to Pc organisms. In healthy AMs, Pc phagocytosis was partially dependent on PAK activation, but dependent on the Rho effector molecule ROCK. These data provide a molecular mechanism for AM mannose receptor-mediated phagocytosis of unopsonized Pc organisms that appears distinct from opsonin-dependent phagocytic receptors. Reduced AM mannose receptor-mediated Cdc42 and Rho activation in the context of HIV infection may represent a mechanism that contributes to the pathogenesis of opportunistic pneumonia.

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The Human Immunodeficiency Virus Type 1 Vpu Protein Inhibits NF-κB Activation by Interfering with βTrCP-mediated Degradation of IκB

Cited by 165 publications

References 63 publications

Inhibition of HOS expression and activities by Wnt pathway

Inhibition of HOS expression and activities by Wnt pathway

Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1

Cdc42 and RhoB Activation Are Required for Mannose Receptor-mediated Phagocytosis by Human Alveolar Macrophages

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