Structural insights into West Nile virus programmed ribosomal frameshifting reveal coordinated regulation by RNA, ribosome, and nascent peptide.

Cryo-EM reveals a previously uncharacterized semi-rotated ribosomal translocation intermediate during West Nile virus -1 programmed ribosomal frameshifting, with 40S partial rotation while tRNAs stay near-canonical.

• Why it matters: How ribosomes traverse the WNV frameshift signal is incompletely understood, limiting mechanistic understanding of how NS1' production is regulated for viral replication and pathogenesis.
• What they did: The authors combined cryo-electron microscopy with RNA structural modeling, molecular dynamics simulations, and functional analyses, resolving a pre-frameshift complex plus four translocation intermediates.
• The result: The frameshift-stimulatory RNA is modeled as a compact, conformationally heterogeneous pseudoknot ensemble, and nascent peptide–exit tunnel interactions reduce frameshifting efficiency when disrupted.

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