XRN1-dependent RNA homeostasis regulates hepatitis D virus

XRN1 loss in hepatoma cells increases dsRNA and ISGs, limiting hepatitis delta virus (HDV) replication, with type I IFN signaling required for the restriction.

• Why it matters: HDV triggers strong interferon programs yet replication is only weakly controlled, leaving the host RNA-sensing and restriction mechanisms unclear.
• What they did: The study used XRN1 knockdown, dsRNA and ISG readouts, type I IFN pathway inhibition, and transcriptomics plus siRNA screening to find anti-HDV effectors.
• The result: DUSP5 and SIRPA were identified as previously unrecognized ISGs with anti-HDV activity, and IFN pathway blockade restored MDA5 expression and rescued HDV replication in XRN1-deficient cells.

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