A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus

Author:

Rutherford Holly A.1,Clarke Amy1,Chambers Emily V.2,Petts Jessica J.1,Carson Euan G.1,Isles Hannah M.1,Duque-Jaramillo Alejandra3ORCID,Renshaw Stephen A.1ORCID,Levraud Jean-Pierre4ORCID,Hamilton Noémie15ORCID

Affiliation:

1. The Bateson Centre, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK

2. The Bioinformatics Core, Faculty of Medicine and Dentistry, University of Sheffield, Sheffield S10 2TN, UK

3. Institute of Microbiology (IMUL), Lausanne University Hospital and University of Lausanne, Rue du Bugnon 48, 1011 Lausanne, Switzerland

4. Macrophages et Développement de l'Immunité, Institut Pasteur, CNRS UMR3738, 25 Rue du Docteur Roux, 75015 Paris,France

5. The Institute of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK

Abstract

ABSTRACT Endogenous retroviruses (ERVs) are fossils left in our genome from retrovirus infections of the past. Their sequences are part of every vertebrate genome and their random integrations are thought to have contributed to evolution. Although ERVs are mainly silenced by the host genome, they have been found to be activated in multiple disease states, such as auto-inflammatory disorders and neurological diseases. However, the numerous copies in mammalian genomes and the lack of tools to study them make defining their role in health and diseases challenging. In this study, we identified eight copies of the zebrafish endogenous retrovirus zferv. We created and characterised the first in vivo ERV reporter line in any species. Using a combination of live imaging, flow cytometry and single-cell RNA sequencing, we mapped zferv expression to early T cells and neurons. Thus, this new tool identified tissues expressing ERV in zebrafish, highlighting a potential role of ERV during brain development and strengthening the hypothesis that ERV play a role in immunity and neurological diseases. This transgenic line is therefore a suitable tool to study the function of ERV in health and diseases.

Funder

Association Européenne contre les Leucodystrophies

Medical Research Council

Sir Jules Thorn Charitable Trust

Agence Nationale de la Recherche

The University of Sheffield Bateson Centre

Publisher

The Company of Biologists

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology and Microbiology (miscellaneous),Medicine (miscellaneous),Neuroscience (miscellaneous)

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