The influenza virus RNA polymerase as an innate immune agonist and antagonist. Author Elizaveta Elshina, Aartjan Velthuis Publication Year 2021 Type Journal Article Abstract Influenza A viruses cause a mild-to-severe respiratory disease that affects millions of people each year. One of the many determinants of disease outcome is the innate immune response to the viral infection. While antiviral responses are essential for viral clearance, excessive innate immune activation promotes lung damage and disease. The influenza A virus RNA polymerase is one of viral proteins that affect innate immune activation during infection, but the mechanisms behind this activity are not well understood. In this review, we discuss how the viral RNA polymerase can both activate and suppress innate immune responses by either producing immunostimulatory RNA species or directly targeting the components of the innate immune signalling pathway, respectively. Furthermore, we provide a comprehensive overview of the polymerase residues, and their mutations, associated with changes in innate immune activation, and discuss their putative effects on polymerase function based on recent advances in our understanding of the influenza A virus RNA polymerase structure. Keywords RNA, Viral, Humans, Signal Transduction, Virus Replication, Viral Proteins, Immunity, Innate, Influenza A virus, Influenza, Human, Immunomodulation, Mitochondria, RNA-Dependent RNA Polymerase, Receptors, Retinoic Acid Journal Cell Mol Life Sci Volume 78 Issue 23 Pages 7237-7256 Date Published 2021 Dec ISSN Number 1420-9071 DOI 10.1007/s00018-021-03957-w Alternate Journal Cell Mol Life Sci PMCID PMC8532088 PMID 34677644 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML