Bluetongue virus infection: activation of the MAP kinase-dependent pathway is required for apoptosis.
Bluetongue virus (BTV) is a double-stranded RNA virus that induces apoptosis both in mammalian cell cultures and in target tissues. Based on information that members of the mitogen-activated protein kinase family (MAPKs) are mediators of apoptosis, we have examined in detail the MAPK-dependent apoptosis in BTV infection. Previously, we have shown that apoptosis in BTV infection requires the participation of mitochondrial apoptotic pathways. In addition, we demonstrated that NF-κB is activated and that its inhibition substantially reduces cellular apoptosis. For the first time, here we demonstrated the activation of MAPKs after BTV infection. Moreover, by pre-treatment with MAPK inhibitors, c-Jun N-terminal kinases (JNKs) and p38 MAPK, but not extracellular signal-related kinase (ERK), significantly decreased the induction of apoptosis. JNK and p38 activation regulated the cytochrome c released from mitochondria and caspase 3 activation. These results strengthen the understanding of BTV infection and contribute to our previous data confirming that BTV infection induces robust apoptosis in mammalian cells and is likely to play a primary role in BTV pathophysiology.
Mortola
Eduardo
E
Inmunología Veterinaria, Facultad de Cs. Veterinarias, Universidad Nacional de La Plata, 60 y 118, 1900 La Plata, Argentina. mortola@fcv.unlp.edu.ar
Larsen
Alejandra
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western / Q000662:veterinary; D001819:Bluetongue / Q000201:enzymology* / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D012756:Sheep; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology
D002070:Butadienes; D009570:Nitriles; C113580:U 0126; D045304:Cytochromes c; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3