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

Linder, Andreas; Bothe, Viktoria; Linder, Nicolas; Schwarzlmueller, Paul; Dahlstrom, Frank; Bartenhagen, Christoph; Dugas, Martin; Pandey, Dharmendra; Thorn-Seshold, Julia; Boehmer, Daniel F. R.; Koenig, Lars M.; Kobold, Sebastian; Schnurr, Max; Raedler, Johannes; Spielmann, Giulia; Karimzadeh, Hadi; Schmidt, Andreas; Endres, Stefan und Rothenfusser, Simon (30. April 2021): Defective Interfering Genomes and the Full-Length Viral Genome Trigger RIG-I After Infection With Vesicular Stomatitis Virus in a Replication Dependent Manner. In: Frontiers in Immunology, Bd. 12, 595390

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Keywords: Vesicular stomatitis virus (VSV); retinoid acid inducible gene I (RIG-I); pattern recognition receptor (PRR); pathogen associated molecular pattern (PAMP); nucleic acid sensing; defective interfering genome
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1664-3224
• Sprache: Englisch