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 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 alpha5 and alpha6 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.
Matarrese
P
P
Department of Ultrastructures, Instituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy.
Conti
L
L
Varano
B
B
Gauzzi
M C
MC
Belardelli
F
F
Gessani
S
S
Malorni
W
W
D008841:Actin Cytoskeleton / Q000502:physiology*; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton; D015870:Gene Expression; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D039482:Integrin alpha5; D039503:Integrin alpha6; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology; D019169:Jurkat Cells; D008928:Mitochondria / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014162:Transfection; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D015820:Cadherins; D016336:Gene Products, vpr; D039482:Integrin alpha5; D039503:Integrin alpha6; D019253:Proto-Oncogene Proteins c-bcl-2; D054325:vpr Gene Products, Human Immunodeficiency Virus