Frontiers in Immunology (Apr 2021)

Defective Interfering Genomes and the Full-Length Viral Genome Trigger RIG-I After Infection With Vesicular Stomatitis Virus in a Replication Dependent Manner

  • Andreas Linder,
  • Andreas Linder,
  • Viktoria Bothe,
  • Nicolas Linder,
  • Paul Schwarzlmueller,
  • Frank Dahlström,
  • Christoph Bartenhagen,
  • Martin Dugas,
  • Dharmendra Pandey,
  • Julia Thorn-Seshold,
  • Julia Thorn-Seshold,
  • Daniel F. R. Boehmer,
  • Lars M. Koenig,
  • Sebastian Kobold,
  • Sebastian Kobold,
  • Max Schnurr,
  • Johannes Raedler,
  • Giulia Spielmann,
  • Hadi Karimzadeh,
  • Hadi Karimzadeh,
  • Andreas Schmidt,
  • Stefan Endres,
  • Stefan Endres,
  • Simon Rothenfusser,
  • Simon Rothenfusser

DOI
https://doi.org/10.3389/fimmu.2021.595390
Journal volume & issue
Vol. 12

Abstract

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Replication competent vesicular stomatitis virus (VSV) is the basis of a vaccine against Ebola and VSV strains are developed as oncolytic viruses. Both functions depend on the ability of VSV to induce adequate amounts of interferon-α/β. It is therefore important to understand how VSV triggers interferon responses. VSV activates innate immunity via retinoic acid-inducible gene I (RIG-I), a sensor for viral RNA. Our results show that VSV needs to replicate for a robust interferon response. Analysis of RIG-I-associated RNA identified a copy-back defective-interfering (DI) genome and full-length viral genomes as main trigger of RIG-I. VSV stocks depleted of DI genomes lost most of their interferon-stimulating activity. The remaining full-length genome and leader-N-read-through sequences, however, still triggered RIG-I. Awareness for DI genomes as trigger of innate immune responses will help to standardize DI genome content and to purposefully deplete or use DI genomes as natural adjuvants in VSV-based therapeutics.

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