Abstract

Keywords

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

P Matarrese¹, L Conti², B Varano², MC Gauzzi², F Belardelli², S Gessani² & W Malorni¹

Correspondence to: W Malorni, Dept. of Ultrastructures, Instituto Superiore di Sanità, V.le Regina Elena, 299 00161 Rome, Italy. Tel: ++39 06 49902905; Fax: ++39 06 49387140; E-mail: Malorni@mclink.it

Edited by ML Gougeon

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 5 and 6 in vpr-transfected 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.

^© Macmillan Publishers Ltd 2000