PUBLICATION
CRISPR/Cas9-induced knockout of tumor necrosis factor-alpha-type I augments viral infection in zebrafish
- Authors
- Kalaichelvan, A., Nadarajapillai, K., Sellaththurai, S.R., Arachchi, U.P.E., Kim, M.J., Jung, S., Lee, J.
- ID
- ZDB-PUB-250109-36
- Date
- 2024
- Source
- Fish & shellfish immunology 157: 110092110092 (Journal)
- Registered Authors
- Keywords
- Antiviral immunity, CRISPR/Cas9, TNF-α1, VHSV, Zebrafish
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/immunology
- Hemorrhagic Septicemia, Viral/genetics
- Hemorrhagic Septicemia, Viral/immunology
- Hemorrhagic Septicemia, Viral/virology
- Tumor Necrosis Factor-alpha*/genetics
- Tumor Necrosis Factor-alpha*/immunology
- Tumor Necrosis Factor-alpha*/metabolism
- Gene Knockout Techniques*
- Immunity, Innate/genetics
- Fish Diseases/genetics
- Fish Diseases/immunology
- Fish Diseases/virology
- Rhabdoviridae Infections/immunology
- Rhabdoviridae Infections/veterinary
- Zebrafish*/genetics
- Zebrafish*/immunology
- Zebrafish*/virology
- Novirhabdovirus*/physiology
- PubMed
- 39716581 Full text @ Fish Shellfish Immunol.
Citation
Kalaichelvan, A., Nadarajapillai, K., Sellaththurai, S.R., Arachchi, U.P.E., Kim, M.J., Jung, S., Lee, J. (2024) CRISPR/Cas9-induced knockout of tumor necrosis factor-alpha-type I augments viral infection in zebrafish. Fish & shellfish immunology. 157:110092110092.
Abstract
Tumor necrosis factor-alpha (TNF-α) is a pleiotropic cytokine with critical roles in inflammation, cell survival, and defense. As a member of the TNF superfamily, it exerts its effects by binding to transmembrane receptors and triggering various downstream signaling pathways. Although TNF-α's involvement in antiviral responses in mammals is well-established, its role in teleost remains poorly understood. This study investigated the contribution of TNF-α1 to antiviral immunity in zebrafish using a tnf-α1(-/-) knockout (KO) line. We challenged both wild-type and tnf-α1(-/-) zebrafish with viral hemorrhagic septicemia virus (VHSV) at both embryonic and adult stages. Mortality was observed at 4 days post-infection (dpi) in tnf-α1-deficient adult fish challenged with 5 × 106 TCID50 (VHSV) and at 5 dpi in adult wild fish challenged with the same concentration. In addition, tnf-α1(-/-) KO adult fish reached the maximum mortality of 100 % at 20 dpi, whereas wild adult fish reached 54 % mortality at the same time point. This increased susceptibility to early mortality was associated with a higher viral burden and altered expression of key immune genes, including the pro-inflammatory cytokines il-6 and il-1β, the anti-inflammatory cytokine il-10, and interferon-related genes such as irf1 and ifn-γ. Our findings demonstrate the crucial role of TNF-α1 in antiviral defense mechanisms in zebrafish and provide valuable insights into the functional conservation of TNF-α signaling across vertebrate species. This knowledge may contribute to the development of strategies to combat viral diseases in fish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping