PUBLICATION
Mitochondrial Antiviral Signaling Protein Plays a Major Role in Induction of the Fish Innate Immune Response against RNA and DNA Viruses
- Authors
- Biacchesi, S., Leberre, M., Lamoureux, A., Louise, Y., Lauret, E., Boudinot, P., and Brémont, M.
- ID
- ZDB-PUB-090601-9
- Date
- 2009
- Source
- Journal of virology 83(16): 7815-7827 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Line
- DNA Viruses/physiology*
- Fish Diseases/immunology
- Fish Diseases/virology*
- Fish Proteins/chemistry
- Fish Proteins/genetics
- Fish Proteins/immunology*
- Fishes/classification
- Fishes/genetics
- Fishes/immunology*
- Fishes/virology
- Immunity, Innate
- Interferons/immunology
- Mitochondrial Proteins/chemistry
- Mitochondrial Proteins/genetics
- Mitochondrial Proteins/immunology*
- Molecular Sequence Data
- Phylogeny
- RNA Viruses/physiology*
- Sequence Alignment
- Signal Transduction*
- Virus Diseases/immunology
- Virus Diseases/veterinary*
- Virus Diseases/virology
- PubMed
- 19474100 Full text @ J. Virol.
Citation
Biacchesi, S., Leberre, M., Lamoureux, A., Louise, Y., Lauret, E., Boudinot, P., and Brémont, M. (2009) Mitochondrial Antiviral Signaling Protein Plays a Major Role in Induction of the Fish Innate Immune Response against RNA and DNA Viruses. Journal of virology. 83(16):7815-7827.
Abstract
Viral infection triggers host innate immune responses through cellular sensor molecules, which activate multiple signaling cascades that induce production of interferons (IFN) and other cytokines. Recent identification of mammalian cytoplasmic viral RNA sensors, such as retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and their mitochondrial adaptor: the mitochondrial antiviral signaling (MAVS) protein, also called IPS-1, VISA and Cardif, highlights the significance of these molecules in the induction of IFN. Teleost fish also possess a strong IFN system but nothing is known concerning the RLRs and their downstream adaptor. In this study, we cloned MAVS cDNAs from several fish species (including salmon and zebrafish) and showed that they were orthologs to mammalian MAVS. We demonstrated that overexpression of these mitochondrial proteins in fish cells led to a constitutive induction of IFN and interferon-stimulated genes (ISGs). MAVS-overexpressing cells were almost fully protected against RNA virus infection with a strong inhibition of both DNA and RNA virus replication (1,000- to 10,000-fold decrease, respectively). Analyses of MAVS deletion-mutants showed that both the N-terminal CARD-like and the C-terminal transmembrane domains, but not the central proline-rich region, were indispensable for MAVS signaling function. In addition, we cloned the cDNAs encoding a RIG-I-like molecule from salmonid and cyprinid cell lines. As MAVS, overexpression in fish cells of RIG-I CARD domains led to a strong induction of both IFN and ISGs conferring to fish cells a full protection against RNA virus infection. This report provides the first demonstration that teleost fish possess a functional RLRs pathway in which MAVS may play a central role in the induction of the innate immune response.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping