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Transient RNA structures cause aberrant influenza virus replication and innate immune activation.

ABSTRACT: During infection, the influenza A virus RNA polymerase produces both full-length and aberrant RNA molecules, such as defective viral genomes (DVGs) and mini viral RNAs (mvRNAs). Subsequent innate immune activation involves the binding of host pathogen receptor retinoic acid-inducible gene I (RIG-I) to viral RNAs. However, it is not clear what factors determine which influenza A virus RNAs are RIG-I agonists. Here, we provide evidence that RNA structures, called template loops (t-loops), stall the viral RNA polymerase and contribute to innate immune activation by mvRNAs during influenza A virus infection. Impairment of replication by t-loops depends on the formation of an RNA duplex near the template entry and exit channels of the RNA polymerase, and this effect is enhanced by mutation of the template exit path from the RNA polymerase active site. Overall, these findings are suggestive of a mechanism involving polymerase stalling that links aberrant viral replication to the activation of the innate immune response.

SUBMITTER: French H

PROVIDER: S-EPMC9462681 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Transient RNA structures cause aberrant influenza virus replication and innate immune activation.

French Hollie H Pitré Emmanuelle E Oade Michael S MS Elshina Elizaveta E Bisht Karishma K King Alannah A Bauer David L V DLV Te Velthuis Aartjan J W AJW

Science advances 20220909 36

During infection, the influenza A virus RNA polymerase produces both full-length and aberrant RNA molecules, such as defective viral genomes (DVGs) and mini viral RNAs (mvRNAs). Subsequent innate immune activation involves the binding of host pathogen receptor retinoic acid-inducible gene I (RIG-I) to viral RNAs. However, it is not clear what factors determine which influenza A virus RNAs are RIG-I agonists. Here, we provide evidence that RNA structures, called template loops (t-loops), stall th ...[more]

PMID: 36083899

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Transient RNA structures cause aberrant influenza virus replication and innate immune activation.

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Transient RNA structures cause aberrant influenza virus replication and innate immune activation.

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