Visna/maedi virus-induced apoptosis involves the intrinsic mitochondrial pathway.
Visna/maedi virus (VMV) infection in sheep choroid plexus cells was associated with the appearance of apoptosis and the implication of a caspase-dependent mechanism. Sheep choroid plexus cells were mock-infected or infected with VMV to examine the time course of activation of the intrinsic pathway of apoptosis. The role of mitochondria and related apoptotic events were evaluated. A drop in mitochondrial potential was observed following mitochondrial membrane permeabilization using JC-1, a fluorescent probe, which shifted its fluorescence emission from green to red. Apoptosis Inducing Factor translocated to the nucleus of infected-cells and this translocation was concomitant with the release of cytochrome c in the cytosol of infected-cells and mitochondrial membrane permeabilization which seemed to be regulated by the p53 pathway. Following phosphorylated p53 induced downregulation of bcl-2. In addition, DNA flow cytometric analyses revealed a sub-G peak characteristic of an apoptotic population that gradually appeared as virus infection progressed. No cell cycle arrest was detected in infected cells while p21 expression increased. It was concluded that VMV apoptosis is mediated in part by the activation of p53 and the intrinsic mitochondrial apoptotic pathway.
Bellet
V
V
Laboratoire de Microbiologie, Faculté de Pharmacie, Limoges, France.
Delebassée
S
S
Bosgiraud
C
C
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D001562:Benzimidazoles / Q000494:pharmacology; D002232:Carbocyanines / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005420:Flavoproteins / Q000032:analysis; D005456:Fluorescent Dyes / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000032:analysis; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D010539:Permeability; D012756:Sheep; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014790:Visna-maedi virus / Q000472:pathogenicity*
D051033:Apoptosis Inducing Factor; D001562:Benzimidazoles; D002232:Carbocyanines; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005420:Flavoproteins; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D045304:Cytochromes c; D004247:DNA