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. 2011 Nov;204 Suppl 3(Suppl 3):S953-6.
doi: 10.1093/infdis/jir325.

The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase

Peter Halfmann  1 , Gabriele Neumann, Yoshihiro Kawaoka
Affiliations

The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase

Peter Halfmann et al. J Infect Dis. 2011 Nov.

Abstract

Type I interferon (IFN) signaling is mediated through several signaling pathways, including the Janus kinase and signal transducer and activator (JAK-STAT) and p38 mitogen-activated protein (MAP) kinase pathways. The VP24 protein of Ebolavirus is an IFN antagonist, blocking type I IFN signaling through the JAK-STAT pathway. Here, we show that, in 293 cells, VP24 also interferes with the p38 MAP kinase pathway by blocking IFN-β-stimulated phosphorylation of p38-α. Similar inhibition was not observed in HeLa cells, suggesting cell type-specific differences in signal transduction.

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Figures

Figure 1.
Figure 1.
Phosphorylation of p38α and ATF-2 in interferon β (IFN-β)–stimulated human embryonic 293 cells. The 293 cells were stimulated with 1000 units/mL of IFN-β for the indicated times. Western blot analysis was performed by using antibodies against phosphorylated p38-α (Thr180/Tyr182), phosphorylated ATF-2 (Thr71), and total cellular p38. The data shown are representative of 2 independent experiments.
Figure 2.
Figure 2.
Zaire ebolavirus (ZEBOV) VP24 prevents p38 mitogen-activated protein (MAP) kinase and ATF-2 phosphorylation in interferon β (IFN-β)–stimulated human embryonic 293 cells. A, ZEBOV VP24 prevents p38 MAP kinase phosphorylation. Cells were transfected with a plasmid encoding ZEBOV VP24 or an empty control vector. Twenty-four hours after transfection, cells were treated with an inhibitor to p38 or JNK or with an equal volume of DMSO. One hour later, cells were stimulated with 1000 units/mL of IFN-β for 30 minutes or remained unstimulated. Western blot analysis was performed by using antibodies against phosphorylated p38α (Thr180/Tyr182) or total cellular p38. B, ZEBOV VP24 prevents ATF-2 phosphorylation. Cells were treated as indicated and described in A. Cell lysates were incubated with an immobilized monoclonal antibody to phosphorylated p38 MAP kinase (Thr180/Tyr182); an in vitro kinase assay was then performed with purified ATF-2 as a substrate. ATF-2 phosphorylation was detected by using Western blot analysis with an antibody to the phosphorylated form of ATF-2 (Thr71).
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