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Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection

2014; National Academy of Sciences; Volume: 111; Issue: 10 Linguagem: Inglês

10.1073/pnas.1400593111

1091-6490

John R. Teijaro, Kevin B. Walsh, Stephanie Rice, Hugh Rosen, Michael B. A. Oldstone,

Viral Infections and Vectors

Significance Cytokine storm plays an essential and commanding role in the clinical outcome and pathogenesis of influenza virus infection. We previously documented that a small molecule that activates sphingosine-1-phosphate-1 receptor (S1P 1 R) signaling is primarily responsible for blunting cytokine storm to protect the infected host from the consequences of influenza infection. In the present study, we map host innate signaling pathways of cytokine storm and chart where along those pathways the drug is effective. We find that the efficacy of S1P 1 R agonist in blunting cytokine storm is through global inhibition downstream of myeloid differentiation primary response gene 88 and IFN-β promoter stimulator-1 signaling.