IAV_KINKTURN / L7Ae

Scope

L7Ae/k-turn, influenza A virus splicing, viral ncRNA, svRNA, segment 7/8 RNA structure, viral RNA editing resistance, and kink-turn-mediated antiviral strategies.

Current Working Model

IAV and likely other orthomyxoviruses contain conserved structured RNA elements in segments 7 and 8 required for efficient viral splicing. L7Ae selectively perturbs this viral splicing system, blocking M2 and NS2/NEP splicing with unexpectedly little host-splicing disruption in remembered cell-based and long-read datasets.

People

• Raman Kaur: current senior scientist lead for L7Ae project.
• Ben tenOever
• Related to IAV FITNESS.

Major Data / Systems

• Doxycycline-inducible MDCK and A549 L7Ae cell lines.
• RNA-seq and proteome with little/no host transcript changes while IAV splicing is blocked.
• Cre/tamoxifen-inducible global L7Ae mouse phenotype: weight loss and sacrifice around day 4–5.
• ES-cell and fibroblast long-read sequencing after 12-hour Cre induction, reportedly minimal host splicing changes.
• IAV challenge with A/California/04/2009.
• pDZ-M1/M2 and pDZ-NS1/2 reporter/rescue constructs.
• L7Ae-ADAR mapping and RIP-seq/prioritization workflows.

Grants / Outputs

• Manuscript arc around native kink-turn in IAV segment 8 enabling L7Ae-mediated splicing blockade.
• ncRNA R01 focused on svRNAs and k-turn/splicing/replication mechanisms.
• Grant document references: 5259200_Egrant.pdf and 4652750_Egrant.pdf.

Pitfalls

• Do not assume L7Ae is a nonspecific global spliceosome inhibitor.
• Do not assume mouse toxicity mechanism is known.
• Do not assume L7Ae protection is interferon priming.

TODO

• Add final figure files, exact grant titles, raw RNA-seq/long-read paths, construct maps, and mouse model details.