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

We have previously shown that CD4(+) T Jurkat cells constitutively expressi ng low levels of the human immunodeficiency virus 1 (HIV-1) vpr protein wer e less susceptible to undergo apoptosis than control cells.(1) In this stud y we have investigated the role of vpr in affecting mechanisms of importanc e in the control of apoptosis, Vpr-expressing clones consistently aggregate d 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 o f cadherin and integrins alpha 5 and alpha 6 in vpr-transfected clones with respect to mock-transfected cells. This up-modulation was specifically blo cked by cell exposure to antisense oligonucleotides targeted at the vpr, In addition, F-actin microfilament cytoskeletal organization, known to be inv olved in cell-cell interaction pathways and in the modulation of cell surfa ce 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 cytosk eleton-dependent cell adhesion pathways, i.e. by inducing anoikis-resistanc e, These particular effects of vpr might enhance the homing, spreading and survival of the infected lymphocytes, thus contributing to virus persistenc e in the course of acute HIV-I infection.