The dissemination of Rift Valley fever virus to the eye and sensory neurons of zebrafish larvae is stat1 dependent

Abstract

The Rift Valley fever virus (RVFV) is listed by the WHO as priority disease and causes haemorrhagic fever, encephalitis, and permanent blindness. 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 log10 viral RNA copies/larva, which was inhibited by antiviral 2'-fluoro-2'-deoxycytidine. The optical transparency of the larvae allowed detection of RVFVeGFP 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 JAK-inhibitor ruxolitinib, as well as knockout of stat1a but not stat1b, enhanced RVFV replication to ~6 log10 viral RNA copies/larva and ultra-bright livers, although without dissemination to sensory neurons or the eye, hereby confirming the critical role of stat1 in RVFV pathogenesis.

A novel zebrafish-basedin vivomodel of Zika virus infection unveils NS4A as a key viral determinant of neuropathogenesis

“…Furthermore, the larval zebrafish brain shares basic neuroanatomical layout with that of mammals. 30 Moreover, zebrafish is permissive to several human viruses (e.g., norovirus, herpes simplex virus, Rift Valley fever virus [31][32][33] ) and phenocopies several human neuropathological diseases such as amyotrophic lateral sclerosis, fronto-temporal dementia and CHARGE syndrome. 28,29,[34][35][36] In this study, we have established a novel zebrafish-based ZIKV infection model to study viral neuropathogenesis in vivo.…”