Mini viral RNAs act as innate immune agonists during influenza virus infection

Nature Microbiology
Aartjan J W Te VelthuisErvin Fodor

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 factors1. However, it is generally accepted that a strong innate immune dysregulation known as 'cytokine storm' contributes to the pathology of infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza viruses of the H5N1 subtype2-4. 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 expression5. 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 i...Continue Reading

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Citations

Feb 15, 2019·Journal of Virology·GuanQun Liu, Yan Zhou
Apr 28, 2019·Tropical Medicine and Infectious Disease·Kanta Subbarao
May 10, 2019·Journal of Virology·Alistair B RussellJesse D Bloom
Aug 14, 2020·PLoS Pathogens·Elizabeth J FayRyan A Langlois
Dec 25, 2019·Cold Spring Harbor Perspectives in Medicine·Ervin Fodor, Aartjan J W Te Velthuis
Oct 26, 2018·Nature Microbiology·William Riedl, Michaela U Gack
Jun 2, 2020·Frontiers in Cellular and Infection Microbiology·Lee K Campbell, Katharine E Magor
Aug 6, 2019·Frontiers in Immunology·Morgan Brisse, Hinh Ly
Mar 24, 2020·Nature Reviews. Immunology·Jan Rehwinkel, Michaela U Gack
May 22, 2020·PLoS Pathogens·Fadi G Alnaji, Christopher B Brooke
Jul 18, 2020·Viruses·Gaurav Malik, Yan Zhou
Jan 13, 2019·Veterinary Sciences·Danyel Evseev, Katharine E Magor
Jul 25, 2019·Nature Microbiology·Bernadeta DadonaiteDavid L V Bauer
Jun 5, 2019·Nature Structural & Molecular Biology·Aartjan J W Te Velthuis
Jan 7, 2021·RNA Biology·Gayan BamunuarachchiLin Liu
Jan 20, 2021·Cellular & Molecular Immunology·Koji OnomotoMitsutoshi Yoneyama
Jan 13, 2021·Science Translational Medicine·Emily SperanzaEmmie de Wit
Feb 10, 2021·Antimicrobial Agents and Chemotherapy·Aartjan J W Te VelthuisVictor Margitich
Nov 19, 2019·Trends in Immunology·Felix Streicher, Nolwenn Jouvenet
Feb 12, 2021·Journal of Virology·Benjamin E Nilsson-PayantBenjamin R tenOever
May 1, 2021·Viruses·Sabrina Weis, Aartjan J W Te Velthuis
Jun 29, 2021·ACS Applied Materials & Interfaces·Vikram GopalAartjan J W Te Velthuis

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Datasets Mentioned

BETA
GTX115046
GTX85488
GTX125926

Methods Mentioned

BETA
transfection
PCR
FCS
Assay

Software Mentioned

ESPript
Prism
biomaRt
GraphPad Prism
R
SAMtools
STAR
bcftools
STAR read
Pymol

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