The HIV-1 vpr protein induces anoikis-resistance by modulating cell adhesion process and microfilament system assembly

Abstract

We have previously shown that CD4 + T Jurkat cells constitutively expressing low levels of the human immunodeficiency virus 1 (HIV-1) vpr protein were less susceptible to undergo apoptosis than control cells.1 In this study we have investigated the role of vpr in affecting mechanisms of importance in the control of apoptosis. Vpr-expressing clones consistently aggregated in clusters with time in culture, whereas mock-transfected cells grew as dispersed cultures. The analysis of adhesion molecules involved in cell-to-cell as well as in cell-substrate interactions showed a higher expression of cadherin and integrins a5 and a6 in vprtransfected clones with respect to mock-transfected cells. This up-modulation was specifically blocked by cell exposure to antisense oligonucleotides targeted at the vpr. In addition, F-actin microfilament cytoskeletal organization, known to be involved in cell-cell interaction pathways and in the modulation of cell surface molecule expression, was significantly improved in vpr-expressing clones, in which filament polymerization was increased. We thus envisage that vpr viral protein can maintain cell survival via a specific activity on cytoskeleton-dependent cell adhesion pathways, i.e. by inducing anoikis-resistance. These particular effects of vpr might enhance the homing, spreading and survival of the infected lymphocytes, thus contributing to virus persistence in the course of acute HIV-1 infection. Cell Death and Differentiation (2000) 7, 25 ± 36.

Cooperative Control of Akt Phosphorylation, bcl-2 Expression, and Apoptosis by Cytoskeletal Microfilaments and Microtubules in Capillary Endothelial Cells

“…Thus, a change in cell shape that alters cytoskeletal structure can itself be a signal for apoptosis. These findings are consistent with the observation that HIV-1 vpr protein appears to prevent anoikis by promoting actin microfilament assembly (Matarrese et al, 2000) and that microtubule disassembly similarly induces apoptosis in fibroblasts (Kook et al, 2000).…”

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

“…[104][105][106][107] Some results clearly associate the subcellular effects of vpr with actin cytoskeleton integrity and function. For instance, vpr expression in Jurkat cells results in remarkable modification of cell-to-cell and cell-to-substrate 108,109 interactions by specifically modifying the actin cytoskeleton, including cortical meshwork, and the expression of certain adhesion molecules (i.e. cadherin and integrins a5 and a6) at the cell surface.…”

“…cadherin and integrins a5 and a6) at the cell surface. 109 In turn, integrins mediate cell migration and cell adhesion, and regulate cell proliferation and apoptosis. Hence, vpr protein could act, via cytoskeleton, as a viral modulator of cell behavior and cell fate.…”

Autoantibodies specific to D4GDI modulate Rho GTPase mediated cytoskeleton remodeling and induce autophagy in T lymphocytes

“…For evaluation of cytoskeleton organization, cells were fixed with 3.7% formaldehyde in PBS with 2% BSA and permeated with 0.5% Triton X-100 in PBS for 10 min at room temperature. For F-actin and G-actin detection, cells were stained at 37 C for 30 min with FITC-phalloidin (SigmaeAldrich), or FITC-DNase I, respectively [30]. For detection of the total amount (F þ G) of actin, cells were incubated with mAb to actin (Chemicon) for 1 h at 4 C.…”