Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells

Carola E. Dehler, Katherine Lester, Giulia Della Pelle, Luc Jouneau, Armel Houel, Catherine Collins, Tatiana Dovgan, Radek Machat, Jun Zou, Pierre Boudinot, Samuel A. M. Martin, Bertrand Collet (Corresponding Author)

Research output: Contribution to journalArticle

Abstract

IFN belong to a group of cytokines specialized in the immunity to viruses. Upon viral infection, type I IFN is produced and alters the transcriptome of responding cells through induction of a set of IFN stimulated genes (ISGs) with regulatory or antiviral function, resulting in a cellular antiviral state. Fish genomes have both type I IFN and type II IFN (IFN-γ), but no type III (λ) IFN has been identified. Their receptors are not simple counterparts of the mammalian type I/II IFN receptors, because alternative chains are used in type I IFN receptors. The mechanisms of the downstream signaling remain partly undefined. In mammals, members of the signal transducer and activator of family of transcription factors are responsible for the transmission of the signal from cytokine receptors, and STAT2 is required for type I but not type II IFN signaling. In fish, its role in IFN signaling in fish remains unclear. We isolated a Chinook salmon (Oncorhynchus tshawytscha) cell line, GS2, with a stat2 gene knocked out by CRISPR/Cas9 genome editing. In this cell line, the induction of ISGs by stimulation with a recombinant type I IFN is completely obliterated as evidenced by comparative RNA-seq analysis of the transcriptome of GS2 and its parental counterpart, EC. Despite a complete absence of ISGs induction, the GS2 cell line has a remarkable ability to resist to viral infections. Therefore, other STAT2-independent pathways may be induced by the viral infection, illustrating the robustness and redundancy of the innate antiviral defenses in fish.
Original languageEnglish
Pages (from-to)465-475
Number of pages11
JournalThe Journal of Immunology
Volume203
Issue number2
Early online date8 Jul 2019
DOIs
Publication statusPublished - 15 Jul 2019

Fingerprint

Fishes
Virus Diseases
Antiviral Agents
Salmon
Cell Line
Clustered Regularly Interspaced Short Palindromic Repeats
Genes
Cytokine Receptors
Gene Expression Profiling
Regulator Genes
Transducers
Transcriptome
Mammals
Immunity
Transcription Factors
Genome
RNA
Cytokines
Viruses

Keywords

  • INTERFERON-STIMULATED GENES
  • MESSENGER-RNA DECAY
  • IMMUNE-RESPONSE
  • RAINBOW-TROUT
  • SHEDS LIGHT
  • IDENTIFICATION
  • GAMMA
  • ALPHA
  • TRANSCRIPTION
  • CRISPR/CAS9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dehler, C. E., Lester, K., Della Pelle, G., Jouneau, L., Houel, A., Collins, C., ... Collet, B. (2019). Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells. The Journal of Immunology, 203(2), 465-475. https://doi.org/10.4049/jimmunol.1801376

Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells. / Dehler, Carola E.; Lester, Katherine; Della Pelle, Giulia; Jouneau, Luc; Houel, Armel; Collins, Catherine; Dovgan, Tatiana; Machat, Radek; Zou, Jun; Boudinot, Pierre; Martin, Samuel A. M.; Collet, Bertrand (Corresponding Author).

In: The Journal of Immunology, Vol. 203, No. 2, 15.07.2019, p. 465-475.

Research output: Contribution to journalArticle

Dehler, CE, Lester, K, Della Pelle, G, Jouneau, L, Houel, A, Collins, C, Dovgan, T, Machat, R, Zou, J, Boudinot, P, Martin, SAM & Collet, B 2019, 'Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells', The Journal of Immunology, vol. 203, no. 2, pp. 465-475. https://doi.org/10.4049/jimmunol.1801376
Dehler CE, Lester K, Della Pelle G, Jouneau L, Houel A, Collins C et al. Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells. The Journal of Immunology. 2019 Jul 15;203(2):465-475. https://doi.org/10.4049/jimmunol.1801376
Dehler, Carola E. ; Lester, Katherine ; Della Pelle, Giulia ; Jouneau, Luc ; Houel, Armel ; Collins, Catherine ; Dovgan, Tatiana ; Machat, Radek ; Zou, Jun ; Boudinot, Pierre ; Martin, Samuel A. M. ; Collet, Bertrand. / Viral Resistance and IFN Signaling in STAT2 Knockout Fish Cells. In: The Journal of Immunology. 2019 ; Vol. 203, No. 2. pp. 465-475.
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AU - Lester, Katherine

AU - Della Pelle, Giulia

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AU - Houel, Armel

AU - Collins, Catherine

AU - Dovgan, Tatiana

AU - Machat, Radek

AU - Zou, Jun

AU - Boudinot, Pierre

AU - Martin, Samuel A. M.

AU - Collet, Bertrand

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