JNK phosphorylation, induced during dengue virus infection, is important for viral infection and requires the presence of cholesterol.
Infection with a broad diversity of viruses often activates host cell signaling pathways including the mitogen-activated protein kinase pathway. The present study established that dengue virus infection of human macrophages activates Jun NH(2)-terminal kinase (JNK) and the p38 MAPKs pathways. The activation was observed at early times after infection and occurs when either infectious or UV-inactivated dengue virus was used. The role of these activated kinases in dengue virus infection was evaluated using specific inhibitors. Inhibition of JNK and p38 kinases did result in a significant reduction in viral protein synthesis and in viral yield. Additionally, lipid rafts disruption induced a strong inhibition of JNK activation. These results suggest that, at early stages after dengue virus infection, MAPKs are activated and that activation of JNK and p38 is required for dengue virus infection.
Ceballos-Olvera
Ivonne
I
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Av. IPN 2508. Col. San Pedro Zacatenco, México City, D.F. C.P. 07360, México.
Chávez-Salinas
Salvador
S
Medina
Fernando
F
Ludert
Juan E
JE
del Angel
Rosa M
RM
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000502:physiology*; D003715:Dengue / Q000209:etiology*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018808:Transcription Factor AP-1; D002784:Cholesterol; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases