Small ruminant lentivirus Tat protein induces apoptosis in caprine cells in vitro by the intrinsic pathway.
The small ruminant lentiviruses, caprine arthritis-encephalitis virus (CAEV) and maedi visna virus (MVV) naturally cause inflammatory disease in goats and sheep, provoking chronic lesions in several different organs. We have previously demonstrated that in vitro infection of caprine cells by CAEV induces apoptosis through the intrinsic pathway (Rea-Boutrois, A., Pontini, G., Greenland, T., Mehlen, P., Chebloune, Y., Verdier, G. and Legras-Lachuer, C. 2008). In the present study, we used Tat deleted viruses and SLRV Tat-expression vectors to show that the SRLV Tat proteins are responsible for this apoptosis. We have also studied the activation of caspases-3, -8 and -9 by fluorescent assays in caprine cells expressing SRLV Tat proteins, and the effects of transfected dominant negative variants of these caspases, to show that Tat-associated apoptosis depends on activation of caspases-3 and -9, but not -8. A simultaneous disruption of mitochondrial membrane potential indicates an involvement of the mitochondrial pathway.
Rea-Boutrois
Angela
A
Université de Lyon, INRA, UMR754, Université Lyon 1, Ecole Nationale Vétérinaire de Lyon, Ecole Pratique des Hautes Etudes, IFR 128, 50 avenue Tony Garnier, 69 366 Lyon cedex 07, France.
Villet
Stéphanie
S
Greenland
Tim
T
Mehlen
Patrick
P
Chebloune
Yahia
Y
Verdier
Gérard
G
Legras-Lachuer
Catherine
C
D000818:Animals; D017209:Apoptosis; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics / Q000472:pathogenicity*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D017353:Gene Deletion; D015696:Gene Products, tat / Q000235:genetics / Q000633:toxicity*; D006041:Goats; D053078:Membrane Potential, Mitochondrial / Q000502:physiology
D015696:Gene Products, tat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9