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bioRxiv · 10.1101/2021.04.08.439059

Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder

Laghi, V.·Rezelj, V.·Boucontet, L.·Boudinot, P.·Salinas, I.·Lutfalla, G.·Vignuzzi, M.·Levraud, J.-P.
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Abstract

Animal models are essential to understand COVID-19 pathophysiology and for pre-clinical assessment of drugs and other therapeutic or prophylactic interventions. We explored the small, cheap and transparent zebrafish larva as a potential host for SARS-CoV-2. Bath exposure, as well as microinjection in the coelom, pericardium, brain ventricle, bloodstream, or yolk, did not result in detectable SARS-CoV-2 replication in wild-type larvae. However, when the virus was inoculated in the swim bladder, a modest increase in viral RNA was observed after 24 hours, suggesting a successful infection in some animals. This was confirmed by immunohistochemistry, with cells positive for SARS-CoV-2 nucleoprotein observed in the swim bladder. Several variants of concern were also tested with no evidence of increased infectivity in our model. Low infectivity of SARS-CoV-2 in zebrafish larvae was not due to the host type I interferon response, as comparable viral loads were detected in type I interferon-deficient animals. Mosaic overexpression of human ACE2 was not sufficient to increase SARS-CoV-2 infectivity in zebrafish embryos or in fish cells in vitro. In conclusion, wild-type zebrafish larvae appear mostly non-permissive to SARS-CoV-2, except in the swim bladder, an aerial organ sharing similarities with the mammalian lung.

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Laghi, V., Rezelj, V., Boucontet, L., Boudinot, P., Salinas, I., Lutfalla, G., Vignuzzi, M., Levraud, J.-P.. 2021-04-10. Exploring zebrafish larvae as a COVID-19 model: probable SARS-COV-2 replication in the swim bladder. https://doi.org/10.1101/2021.04.08.439059

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