This study investigates how influenza A virus mRNAs are exported from the nucleus to the cytoplasm by testing the involvement of the cellular NXF1/TAP export pathway. Influenza produces 10 different mRNAs with variable structures: most lack introns, while two segments contain introns but remain largely unspliced, and two are fully spliced. Using RNA interference and drug treatments, researchers found that individual viral mRNAs show differential dependence on NXF1. Late gene mRNAs (segments 4, 7, 8 encoding HA, M1/M2, and NS1/NS2) strongly require NXF1 for nuclear export, while early intronless gene mRNAs (particularly segment 5 encoding NP) show minimal NXF1 dependence. The helicase UAP56 is specifically required for segments 7 and 8 export but not others, while Aly shows minimal involvement. CRM1-dependent export was ruled out based on leptomycin B resistance. These findings demonstrate that influenza virus co-opts the primary cellular mRNA export machinery for a subset of its transcripts, particularly late genes, with recruitment mechanisms varying among different viral mRNAs.

Key findings

• Influenza A virus mRNAs display differential and selective dependence on the cellular NXF1/TAP export pathway, with late gene transcripts (HA, M1, M2, NS1) strongly requiring NXF1 and early intronless transcripts (especially NP) showing minimal dependence.
• The helicase UAP56 is specifically required for export of segments 7 and 8 mRNAs but not for segments 1, 4, or 5, indicating varied recruitment mechanisms among viral transcripts.
• NXF1 depletion reduces viral protein synthesis of late genes by >3-fold while having minimal effect on early gene products, correlating with mRNA nuclear export efficiency.
• The adaptor protein Aly plays little to no role in influenza mRNA export despite its importance in cellular mRNA export, suggesting alternative recruitment mechanisms for NXF1.
• CRM1-dependent export is not involved in influenza mRNA trafficking, as evidenced by leptomycin B resistance.