The role of the circadian clock gene cry1 in the regulation of the antiviral response in zebrafish (Danio rerio) larvae.
| Title: | The role of the circadian clock gene cry1 in the regulation of the antiviral response in zebrafish (Danio rerio) larvae. |
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| Authors: | Mazur M; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Lojasiewicza 11, 30-348, Krakow, Poland.; Pooranachandran N; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland.; Zawisza M; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Lojasiewicza 11, 30-348, Krakow, Poland.; Baran Z; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Lojasiewicza 11, 30-348, Krakow, Poland.; Michalik A; Department of Developmental Biology and Invertebrate Morphology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland.; Adamek M; Fish Disease Research Unit, Institute for Parasitology, University of Veterinary Medicine Hannover, Bunteweg 17, 30559, Hannover, Germany.; Marcinkowska M; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Lojasiewicza 11, 30-348, Krakow, Poland.; Surachetpong W; Institute of Aquaculture, University of Stirling, Stirling, FK9 4LA, UK.; Prajsnar TK; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland.; Rakus K; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland.; Pijanowski L; Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Krakow, Poland.; Chadzinska M; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Gronostajowa 9, 30-387, Krakow, Poland. Electronic address: magdalena.chadzinska@uj.edu.pl. |
| Source: | Fish & shellfish immunology [Fish Shellfish Immunol] 2026 Mar; Vol. 170, pp. 111098. Date of Electronic Publication: 2026 Jan 03. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Academic Press Country of Publication: England NLM ID: 9505220 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9947 (Electronic) Linking ISSN: 10504648 NLM ISO Abbreviation: Fish Shellfish Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London ; New York : Academic Press, c1991- |
| MeSH Terms: | Zebrafish*/immunology ; Zebrafish*/genetics ; Circadian Clocks*/genetics ; Cryptochromes*/genetics ; Cryptochromes*/immunology ; Fish Diseases*/immunology ; Fish Diseases*/virology ; Immunity, Innate*/genetics ; Zebrafish Proteins*/genetics ; Zebrafish Proteins*/immunology; Larva/immunology ; Larva/genetics ; Larva/growth & development ; DNA Virus Infections/immunology ; DNA Virus Infections/veterinary ; Animals |
| Abstract: | All living organisms are influenced by the circadian clock. This mechanism generates rhythms that affect organismal processes involved in cellular activity, behavior and immunity. In the present study we investigated the function of the circadian clock genes: cry1a and cry1b in zebrafish larvae, focusing on their roles in early development, behavior, microbiota composition, and antiviral immune response. Using Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR-associated protein 9 (CRISPR-Cas9) gene editing, we generated zebrafish lines with targeted mutations in cry1a and cry1b genes and found that cry1 genes are not essential for larval survival or development. However, both mutations led to significant behavioral changes, with mutant larvae exhibiting increased locomotor activity compared to their wild type (WT) counterparts. Microbiome analysis revealed that cry1a mutation, in particular, resulted in a higher abundance of Proteobacteria in the larval microbiota. When challenged with Tilapia lake virus (TiLV), both cry1a and cry1b mutants displayed increased viral loads and reduced survival rates, indicating a compromised antiviral response. Specifically, cry1a mutants had lower initial expression of tlr22, while cry1b mutants showed reduced gene expression of antiviral Mxa at later stages post-infection, both contributing to decreased resistance against TiLV. Overall, the findings demonstrate that while cry1a and cry1b mutations do not significantly affect an early development, both genes play important roles in regulating behavior, shaping the microbiome, and modulating innate antiviral immunity in zebrafish larvae. The study highlights the multifaceted functions of circadian clock genes in vertebrate physiology and immunity.; (Crown Copyright © 2026. Published by Elsevier Ltd. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Antiviral response; Biological clock; Microbiome; TiLV; Zebrafish; cry1 |
| Substance Nomenclature: | 0 (Cryptochromes); 0 (Zebrafish Proteins) |
| Entry Date(s): | Date Created: 20260106 Date Completed: 20260204 Latest Revision: 20260204 |
| Update Code: | 20260205 |
| DOI: | 10.1016/j.fsi.2026.111098 |
| PMID: | 41490763 |
| Database: | MEDLINE |
Journal Article