Yago Gomes, Institut National de la Recherche Scientifique

Yago C P Gomes1 , Aïcha A Sow1, Nicolas Pilon2 , Shunmoogum A Patten1, Laurent Chatel-Chaix1. 1Institut National de la Recherche Scientifique, 2Université du Québec à Montréal.

Damaging & Spreading

Zika virus (ZIKV) infection during pregnancy can cause congenital Zika syndrome, yet mechanisms of neuropathogenesis remain poorly defined. We recently established a zebrafish ZIKV infection model recapitulating microcephaly, neural progenitor cell (NPC) infection, and NPC depletion. We showed infection alters the transcriptomic profile of NPC and immunostaining indicates the virus is confined to a subset of NPCs and other neural populations, motivating higher-resolution profiling. To define infection-modulated subpopulations, we performed single-cell RNA sequencing (scRNA-seq) using complementary strategies. scRNA-seq of dissociated whole-head cells from pooled 2 dpf embryos uncovered transcriptional remodeling across NPCs, retinal progenitors, and differentiating neurons. Differential and trajectory-based analyses revealed disrupted signatures governing proliferation and neuronal commitment, including altered expression of progenitor maintenance markers her4/her15 and proneural markers neurog1/neurod6. To increase resolution within progenitor states, we performed scRNA-seq on purified radial glial cells (including NPCs) from 1 dpf Tg(gfap:GFP) embryos, identifying a nestin-expressing, neuron-committed population with downregulation of TGF-β pathway components. Together, our scRNA-seq analyses indicate that ZIKV induces cell state-specific transcriptional remodeling across early progenitors and differentiating neurons, with altered regulatory signatures linked to proliferation and neuronal commitment. These results support a model in which ZIKV disrupts neurogenic progression at defined maturation stages, and highlight zebrafish as a tractable in vivo platform to map neurotropism and test mechanisms underlying microcephaly. Finally, ongoing scRNA-seq of sorted Tg(nestin:GFP) cells using a dual host/viral RNA capture protocol will directly link viral burden to host responses.