How interferon throttles sterol synthesis in antiviral defense

Type I interferon couples viral sensing to down-regulation of the sterol pathway’s mevalonate–isoprenoid arm, limiting viral growth.

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What host pathway did type I IFN couple to upon viral infection?

The sterol biosynthesis pathway, especially the mevalonate–isoprenoid arm.

What metabolite rescue blocked antiviral effects of sterol down-regulation?

Excess mevalonate (not cholesterol).

What fraction of IFNγ down-regulated lipogenic transcripts were sterol-related?

40% (14/35).

Which receptor was required for sterol down-regulation after infection?

Type I interferon receptor (IFNAR1).

What happens to SREBP2 with infection/IFN?

Mature SREBP2 protein and Srebf2 transcription fall in an IFNAR-dependent manner.

Which cytokine class specifically down-regulated sterol genes among those tested?

IFNβ (and IFNγ), not IL1β, TNF, or IL6.

What in vivo intervention reduced mCMV titres?

Simvastatin treatment lowered viral titres in multiple organs.

Is the antiviral effect explained by cholesterol starvation alone?

No—cholesterol/squalene feeding failed to rescue, while geranylgeraniol did.

What cellular model was central?

Primary bone-marrow–derived macrophages infected with murine CMV.

What signaling kinase was required for transcriptional sterol down-regulation?

Tyk2.

How large were transcript reductions for sterol genes?

Modest (~1.3- to 5-fold with infection over 24 h).