Ter Horst Sebastiaan, Siekierska Aleksandra, De Meulemeester Ann-Sofie, Cuvry Arno, Cools Laura, Neyts Johan, de Witte Peter, Rocha-Pereira Joana
Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Viruses. 2025 Jan 11;17(1):87. doi: 10.3390/v17010087.
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 viral RNA copies/larva, which was inhibited by the antiviral 2'-fluoro-2'-deoxycytidine. The optical transparency of the larvae allowed detection of RVFV 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 but not , enhanced RVFV replication to ~6 log viral RNA copies/larva and ultra-bright livers, although without dissemination to sensory neurons or the eye, thereby confirming the critical role of in RVFV pathogenesis.
裂谷热病毒（RVFV）可引发出血热、脑炎和永久性失明，已被世界卫生组织列为重点病原体。为研究RVFV的发病机制并鉴定小分子抗病毒药物，我们利用斑马鱼幼体建立了一种新型体内模型。通过心包注射RVFV，每只幼体可产生约4个对数级的病毒RNA拷贝，抗病毒药物2'-氟-2'-脱氧胞苷可对其产生抑制作用。幼体的光学透明性使得能够在肝脏和感觉神经系统（包括视顶盖和视网膜）中检测到RVFV，但在大脑或脊髓中则无法检测到。因此，RVFV导致的失明可能是由于眼睛和外周神经元直接受损，而非大脑。使用JAK抑制剂鲁索替尼进行治疗，以及敲除 而非 ，可使RVFV复制增加至约6个对数级的病毒RNA拷贝/幼体，并使肝脏超亮，尽管病毒未扩散至感觉神经元或眼睛，从而证实了 在RVFV发病机制中的关键作用。
