The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent
The Rift Valley fever virus (RVFV) causes haemorrhagic fever, encephalitis, and permanent blindness and has been listed by the WHO as a priority pathogen. To study RVFV pathogenesis and identify small-molecule antivirals, we established a novel In Vivo model using zebrafish larvae. Pericardial injec...
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| author | Sebastiaan ter Horst Aleksandra Siekierska Ann-Sofie De Meulemeester Arno Cuvry Laura Cools Johan Neyts Peter de Witte Joana Rocha-Pereira |
| author_facet | Sebastiaan ter Horst Aleksandra Siekierska Ann-Sofie De Meulemeester Arno Cuvry Laura Cools Johan Neyts Peter de Witte Joana Rocha-Pereira |
| author_sort | Sebastiaan ter Horst |
| collection | DOAJ |
| description | The Rift Valley fever virus (RVFV) causes haemorrhagic fever, encephalitis, and permanent blindness and has been listed by the WHO as a priority pathogen. To study RVFV pathogenesis and identify small-molecule antivirals, we established a novel In Vivo model using zebrafish larvae. Pericardial injection of RVFV resulted in ~4 log<sub>10</sub> viral RNA copies/larva, which was inhibited by the antiviral 2′-fluoro-2′-deoxycytidine. The optical transparency of the larvae allowed detection of RVFV<sub>eGFP</sub> in the liver and sensory nervous system, including the optic tectum and retina, but not the brain or spinal cord. Thus, RVFV-induced blindness likely occurs due to direct damage to the eye and peripheral neurons, rather than the brain. Treatment with the JAK-inhibitor ruxolitinib, as well as knockout of <i>stat1a</i> but not <i>stat1b</i>, enhanced RVFV replication to ~6 log<sub>10</sub> viral RNA copies/larva and ultra-bright livers, although without dissemination to sensory neurons or the eye, thereby confirming the critical role of <i>stat1</i> in RVFV pathogenesis. |
| format | Article |
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| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-38928ed4353a47c299731f7fdddf3fb02025-01-24T13:52:33ZengMDPI AGViruses1999-49152025-01-011718710.3390/v17010087The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-DependentSebastiaan ter Horst0Aleksandra Siekierska1Ann-Sofie De Meulemeester2Arno Cuvry3Laura Cools4Johan Neyts5Peter de Witte6Joana Rocha-Pereira7Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, BelgiumThe Rift Valley fever virus (RVFV) causes haemorrhagic fever, encephalitis, and permanent blindness and has been listed by the WHO as a priority pathogen. To study RVFV pathogenesis and identify small-molecule antivirals, we established a novel In Vivo model using zebrafish larvae. Pericardial injection of RVFV resulted in ~4 log<sub>10</sub> viral RNA copies/larva, which was inhibited by the antiviral 2′-fluoro-2′-deoxycytidine. The optical transparency of the larvae allowed detection of RVFV<sub>eGFP</sub> in the liver and sensory nervous system, including the optic tectum and retina, but not the brain or spinal cord. Thus, RVFV-induced blindness likely occurs due to direct damage to the eye and peripheral neurons, rather than the brain. Treatment with the JAK-inhibitor ruxolitinib, as well as knockout of <i>stat1a</i> but not <i>stat1b</i>, enhanced RVFV replication to ~6 log<sub>10</sub> viral RNA copies/larva and ultra-bright livers, although without dissemination to sensory neurons or the eye, thereby confirming the critical role of <i>stat1</i> in RVFV pathogenesis.https://www.mdpi.com/1999-4915/17/1/87bunyavirusrift valley fever virusinnate immunityzebrafishpathogenesis |
| spellingShingle | Sebastiaan ter Horst Aleksandra Siekierska Ann-Sofie De Meulemeester Arno Cuvry Laura Cools Johan Neyts Peter de Witte Joana Rocha-Pereira The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent Viruses bunyavirus rift valley fever virus innate immunity zebrafish pathogenesis |
| title | The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent |
| title_full | The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent |
| title_fullStr | The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent |
| title_full_unstemmed | The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent |
| title_short | The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent |
| title_sort | dissemination of rift valley fever virus to the eye and sensory neurons of zebrafish larvae is stat1 dependent |
| topic | bunyavirus rift valley fever virus innate immunity zebrafish pathogenesis |
| url | https://www.mdpi.com/1999-4915/17/1/87 |
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