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Linder, A.* ; Bothe, V.* ; Linder, N.* ; Schwarzlmueller, P.* ; Dahlström, F.* ; Bartenhagen, C.* ; Dugas, M.* ; Pandey, D.* ; Thorn-Seshold, J. ; Boehmer, D.F.R.* ; Koenig, L.M.* ; Kobold, S.* ; Schnurr, M.* ; Raedler, J.* ; Spielmann, G.* ; Karimzadeh, H. ; Schmidt, A.* ; Endres, S. ; Rothenfußer, S.

Defective interfering genomes and the full-length viral genome trigger RIG-I after infection with vesicular stomatitis virus in a replication dependent manner.

Front. Immunol. 12:595390 (2021)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Defective Interfering Genome ; Nucleic Acid Sensing ; Pathogen Associated Molecular Pattern (pamp) ; Pattern Recognition Receptor (prr) ; Retinoid Acid Inducible Gene I (rig-i) ; Vesicular Stomatitis Virus (vsv); Stranded-rna

ISSN (print) / ISBN 1664-3224

e-ISSN 1664-3224

Journal Frontiers in Immunology

Quellenangaben Volume: 12, Article Number: 595390

Publisher Frontiers

Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)

Grants international doctoral program "iTarget: Immunotargeting of cancer" - Elite Network of Bavaria
Marie-Sklodowska-Curie Training Network for the Immunotherapy of Cancer (IMMUTRAIN) - H2020 program of the European Union
Else Kroner-Fresenius-Stiftung
Friedrich-Baur-Stiftung
Deutsche Forschungsgemeinschaft
DFG
Einheit fur Klinische Pharmakologie (EKLIP), Helmholtz Zentrum Munchen, Neuherberg, Germany