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TitleRegulatory hotspot on the influenza A virus polymerase revealed through the structure of the NEP-polymerase complex.
Journal, issue, pagesSci Adv, Vol. 12, Issue 4, Page eaeb4073, Year 2026
Publish dateJan 23, 2026
AuthorsAlison Rep / Fangzheng Wang / Kuang-Yu Chen / Loïc Carrique / Jane Sharps / Jonathan M Grimes / Ervin Fodor /
PubMed AbstractInfluenza A virus (IAV) transcribes and replicates its segmented RNA genome in the host nucleus within viral ribonucleoproteins (vRNPs), which are exported for virion assembly. The nuclear export ...Influenza A virus (IAV) transcribes and replicates its segmented RNA genome in the host nucleus within viral ribonucleoproteins (vRNPs), which are exported for virion assembly. The nuclear export protein (NEP) is essential for this process and also regulates viral RNA synthesis, implicating a direct interaction with the viral RNA polymerase. Here, we present a 2.5-Å cryogenic electron microscopy structure of NEP bound to the IAV polymerase and demonstrate that NEP alone is sufficient to promote vRNP export, with the viral matrix protein 1 enhancing export efficiency. NEP forms a four-helix bundle that binds at the interface of the PA C-terminal domain and PB1 N terminus of the polymerase. The NEP binding site at this interface overlaps with those for the host ANP32 and the C-terminal domain of RNA polymerase II, indicating that it functions as a regulatory hotspot coordinating transitions of the viral polymerase between RNA synthesis and nuclear export, revealing a critical layer of control in the IAV replication cycle.
External linksSci Adv / PubMed:41576158 / PubMed Central
MethodsEM (single particle)
Resolution2.53 - 2.93 Å
Structure data

54287

9rve

EMDB-54287, PDB-9rve:
Structure of human 1918 influenza A polymerase heterotrimer in complex with 1918 NEP.
Method: EM (single particle) / Resolution: 2.53 Å

54376

9ryc

EMDB-54376, PDB-9ryc:
Structure of human 1918 influenza A polymerase heterotrimer in complex with WSN NEP.
Method: EM (single particle) / Resolution: 2.93 Å

Source
  • influenza a virus (a/brevig mission/1/1918(h1n1))
KeywordsVIRAL PROTEIN / influenza virus / nuclear export / NEP / NS2 / 1918 polymerase / spanish Flu / viral polymerase / cryo-EM

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