JNK phosphorylation, induced during dengue virus infection, is important for viral infection and requires the presence of cholesterol

Abstract

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.

Virus-Induced Ca 2+ Influx Extends Survival of West Nile Virus-Infected Cells

“…Consistent with what has previously been reported for UV-inactivated enveloped virions (9,27,36,39,52), the data obtained in this study indicate that UV-inactivated WNV attaches to unknown receptors and activates early signaling events, but only transiently.…”

Micronutrients and Dengue

“…27 The activation of MAPKs c-Jun N-terminal kinase (JNK) and p38 pathways is necessary for the virus to successfully replicate and infect macrophages that release proinflammatory cytokines, which are associated with the disease manifestations of capillary leak syndrome and hemorrhagic tendencies. 28,29 Therefore, down-regulation of this pathway by vitamin D3 would result in the reduction of the numbers of infected cells and specific proinflammatory cytokines that were observed in this study as well as hypothetically, a reduction in clinical severity of the disease.…”

Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner

“…Previous reports have demonstrated the activation of two MAPKs, p38 and ERK1/2, in DENV-infected endothelial cells, leading to the up-regulation of protease-activated receptor type-1 and tissue factor receptor via phosphorylation and suggesting an involvement in DENV pathogenesis (41). Interestingly, a recent report showed a link between cholesterol and JNK signaling and demonstrated its importance for DENV replication in infected macrophages (42). In addition, several studies on WNV have reported the cellular redistribution of cholesterol and its requirement for viral entry and replication (43,44).…”