An Antiviral Sterol

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Science  18 Jan 2013:
Vol. 339, Issue 6117, pp. 253
DOI: 10.1126/science.339.6117.253-a

After viral infection, the production of type I interferons (IFNs) induces an antiviral state through the induction of a large network of genes. How these different pathways induce viral control, however, is incompletely characterized. By using microarray analysis to look for genes induced in response to IFN treatment of mouse macrophages, Liu et al. identified Ch25h, which encodes cholesterol-25-hydroxylase, as an IFN-stimulated gene with antiviral activity. CH25H mediates these effects by catalyzing the oxidation of cholesterol to the soluble oxysterol 25-hydroxycholesterol (25HC). Pretreatment of cells with 25HC was able to protect these cells against infection with a variety of enveloped viruses, including HIV-1. Further characterization of the mechanism of inhibition revealed that 25HC blocked membrane fusion between the virus and host cells. Viral infection of Ch25h-deficient mice and treatment of HIV-1–infected humanized mice with 25HC confirmed the physiological relevance of the authors' findings. Similar findings were reported by Blanc et al., who also revealed that the transcription factor Stat1 was required for IFN-dependent induction of 25HC.

Immunity 10.1016/j.immuni.2012.11.005; 10.1016/j.immuni.2012.11.004 (2012).

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