@article{179156,
  keywords = {Animals, Mutation, RNA, Viral, Cell Line, Female, Male, Interferon-beta, Viral Proteins, Virus Replication, Immunity, Innate, Cytokines, Influenza A virus, DEAD Box Protein 58, Ferrets, Orthomyxoviridae Infections},
  author = {Aartjan Te Velthuis and Joshua Long and David Bauer and Rebecca Fan and Hui-Ling Yen and Jane Sharps and Jurre Siegers and Marian Killip and Hollie French and Maria Jos{\'e} Oliva-Mart{\'\i}n and Richard Randall and de Emmie Wit and van Debby Riel and Leo Poon and Ervin Fodor},
  title = {Mini viral RNAs act as innate immune agonists during influenza virus infection},
  abstract = { The molecular processes that determine the outcome of influenza virus infection in humans are multifactorial and involve a complex interplay between host, viral and bacterial factors. However, it is generally accepted that a strong innate immune dysregulation known as {\textquoteright}cytokine storm{\textquoteright} contributes to the pathology of infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza viruses of the H5N1 subtype. The RNA sensor retinoic acid-inducible gene I (RIG-I) plays an important role in sensing viral infection and initiating a signalling cascade that leads to interferon expression. Here, we show that short aberrant RNAs (mini viral RNAs (mvRNAs)), produced by the viral RNA polymerase during the replication of the viral RNA genome, bind to and activate RIG-I and lead to the expression of interferon-β. We find that erroneous polymerase activity, dysregulation of viral RNA replication or the presence of avian-specific amino acids underlie mvRNA generation and cytokine expression in mammalian cells. By deep sequencing RNA samples from the lungs of ferrets infected with influenza viruses, we show that mvRNAs are generated during infection in vivo. We propose that mvRNAs act as the main agonists of RIG-I during influenza virus infection. },
  year = {2018},
  journal = {Nat Microbiol},
  volume = {3},
  pages = {1234-1242},
  month = {11/2018},
  issn = {2058-5276},
  doi = {10.1038/s41564-018-0240-5},
  language = {eng},
}