RNA structures regulate norovirus life cycle and enable rational attenuation in vivo.

Conserved structured RNA motifs across the murine norovirus genome regulate replication and gene expression, and targeted disruption reduces viral replication and viral RNA levels in infection models.

• Why it matters: Systematic mapping of viral RNA structures during infection and their in vivo roles in fitness and immune recognition remain limited, limiting rational antiviral vaccine or therapeutic design.
• What they did: The study orthogonally maps and functionally interrogates structured RNA elements across the murine norovirus genome using in-cell chemical probing, then tests targeted structural disruptions in cell culture and animal infection models.
• The result: Disrupting specific structural elements reduces viral replication in cell culture, modulates translation in cis, and decreases viral RNA levels in animal infection models, enabling a genetically stable attenuated virus that elicits protective immunity and limits replication upon secondary challenge.

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