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 α5 and α6 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.
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Abbreviations
- HIV-1:
-
human immunodeficiency virus 1
- SIV:
-
simian immunodeficiency virus
- FCS:
-
foetal calf serum
- AO:
-
antisense phosphorothioate oligodeoxynucleotides
- SO:
-
sense phosphorothioate oligodeoxynucleotides
- CHX:
-
cycloheximide
- TNF-α:
-
tumor necrosis factor-α
- EDTA:
-
ethylenediamine tetraacetate
- PBS:
-
phosphate buffered saline
- BSA:
-
bovine serum albumin
- SEM:
-
scanning electron microscopy
- ECM:
-
extra cellular matrix
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Acknowledgements
This work was partially supported by X and XI AIDS Project to W Malorni and F Belardelli. We thank Mrs Maria Letizia Semeraro and Mr Marco Sabatini for their helpful technical assistance.
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Matarrese, P., Conti, L., Varano, B. et al. The HIV-1 vpr protein induces anoikis-resistance by modulating cell adhesion process and microfilament system assembly. Cell Death Differ 7, 25–36 (2000). https://doi.org/10.1038/sj.cdd.4400616
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DOI: https://doi.org/10.1038/sj.cdd.4400616
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