CD95/phosphorylated ezrin association underlies HIV-1 GP120/IL-2-induced susceptibility to CD95(APO-1/Fas)-mediated apoptosis of human resting CD4+T lymphocytes

Luciani, Francesca; Matarrese, Paola; Giammarioli, Anna Maria; Lugini, Luana; Lozupone, Francesco; Federici, Cristina; Iessi, Elisabetta; Malorni, Walter; Fais, Stefano

doi:10.1038/sj.cdd.4401374

Cited by 33 publications

(33 citation statements)

References 56 publications

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“…Similarly, a lower level of VEGFR-3 activation by fibronectin as compared with VEGF-C was observed in prior studies (35,36). Likewise, modest stimulation of receptor tyrosine kinases by other viral proteins, as compared with their natural ligands, has been observed in T cells and endothelial cells (52)(53)(54). However, a significantly enhanced association of VEGFR-3 and ␣ 3 was observed in cells stimulated with gB (Fig.…”

Section: The Gb-induced Activation Of Vegfr-3 Is Inhibited By Blockinsupporting

confidence: 73%

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Zhang¹,

Wang²,

Chandran

et al. 2005

Journal of Biological Chemistry

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Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8) is the etiologic agent of Kaposi's sarcoma, an endothelial neoplasm. This ␥-herpesvirus encodes for several unique proteins that alter target cell function, including the virion envelope-associated glycoprotein B (gB). Glycoprotein B has an RGD (Arg-Gly-Asp) motif at the extracellular amino terminus region and binds to the ␣ 3 ␤ 1 surface integrin, which enhances virus entry. We now report that gB can activate the vascular endothelial growth factor receptor 3 (VEGFR-3) on the surface of microvascular endothelial cells and trigger receptor signaling, which can modulate endothelial migration and proliferation. Furthermore, we observed that VEGFR-3 expression and activation enhance KSHV infection and participate in KSHV-mediated transformation. These functional changes in the endothelium may contribute to the pathogenesis of Kaposi's sarcoma and suggest that interventions that inhibit gB activation of VEGFR-3 could be useful in the treatment of this neoplasm.

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Section: The Gb-induced Activation Of Vegfr-3 Is Inhibited By Blockinsupporting

confidence: 73%

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Zhang¹,

Wang²,

Chandran

et al. 2005

Journal of Biological Chemistry

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“…Importantly, in vitro treatment with HIV-1 gp120 can induce: (i) lymphocyte polarization with uropod formation; (ii) CD95/ezrin colocalization on lymphocyte uropods and (iii) a stable ezrin phosphorylation, with the presence of an 80 kDa tyrosinephosphorylated protein corresponding to ezrin in CD95 immunoprecipitates (Figure 3a). 92 All these events determine a high susceptibility to CD95-mediated apoptosis (Figure 3b). Thus, gp120/gp41 complexes, shed from both infected cells and HIV-1 virions, may interact with receptor molecules expressed also on uninfected cells and contribute in this way to the depletion of both infected and bystander CD4 þ cells in acquired immunodeficiency syndrome (AIDA).…”

Section: Gp120-induced Cytoskeleton-mediated T-cell Polarizationmentioning

confidence: 99%

Human immunodeficiency virus (HIV)-1 proteins and cytoskeleton: partners in viral life and host cell death

Matarrese

Malorni

2005

Cell Death Differ

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Cytoskeletal components play a major role in the human immunodeficiency virus-1 (HIV-1) infection. A wide variety of molecules belonging to the microfilament system, including actin filaments and actin binding proteins, as well as microtubules have a key role in regulating both cell life and death. Cell shape maintenance, cell polarity and cell movements as well as cytoplasmic trafficking of molecules determining cell fate, including apoptosis, are in fact instructed by the cytoskeleton components. HIV infection and viral particle production seem to be controlled by cytoskeleton as well. Furthermore, HIV-associated apoptosis failure can also be regulated by the actin network function. In fact, HIV protein gp120 is able to induce cytoskeleton-driven polarization, thus sensitizing T cells to CD95/Fas-mediated apoptosis. The microfilament system seems thus to be a sort of cytoplasmic supervisor of the viral particle, the host cell and the bystander cell's very fate. Cell Death and Differentiation (2005) 12, 932-941.

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“…In addition to FasL regulation, several HIVencoded molecules have been shown to induce apoptosis of both infected and uninfected T cells by triggering death receptor-mediated or mitochondrial apoptotic pathways in vitro (17). Interestingly, HIV gp120 shares the ability of IL-7 or TCR triggering to induce Fas-ezrin association on T cells, and this mechanism might play an important role in inducing apoptosis sensitivity in bystander T cells (53).…”

Section: Discussionmentioning

confidence: 99%

Potential Role for IL-7 in Fas-Mediated T Cell Apoptosis During HIV Infection

Fluur

Milito

Fry

et al. 2007

The Journal of Immunology

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IL-7 promotes survival of resting T lymphocytes and induces T cell proliferation in lymphopenic conditions. As elevated IL-7 levels occur in HIV-infected individuals in addition to high Fas expression on T cells and increased sensitivity to Fas-induced apoptosis, we analyzed whether IL-7 has a regulatory role in Fas-mediated T cell apoptosis. We show that IL-7 up-regulates Fas expression on naive and memory T cells through a mechanism that involves translocation of Fas molecules from intracellular compartments to the cell membrane. IL-7 induced the association of Fas with the cytoskeletal component ezrin and a polarized Fas expression on the cell surface. The potential role of IL-7 in Fas up-regulation in vivo was verified in IL-7-treated macaques and in HIV-infected or chemotherapy treated patients by the correlation between serum IL-7 levels and Fas expression on T cells. IL-7 treatment primed T cells for Fas-induced apoptosis in vitro and serum IL-7 levels correlated with the sensitivity of T cells to Fas-induced apoptosis in HIV-infected individuals. Our data suggest an important role for IL-7 in Fas-mediated regulation of T cell homeostasis. Elevated IL-7 levels associated with lymphopenic conditions, including HIV-infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis.

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CD95/phosphorylated ezrin association underlies HIV-1 GP120/IL-2-induced susceptibility to CD95(APO-1/Fas)-mediated apoptosis of human resting CD4+T lymphocytes

Cited by 33 publications

References 56 publications

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Human immunodeficiency virus (HIV)-1 proteins and cytoskeleton: partners in viral life and host cell death

Potential Role for IL-7 in Fas-Mediated T Cell Apoptosis During HIV Infection

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