Real-Time Whole-Body Visualization of Chikungunya Virus Infection and Host Interferon Response in Zebrafish

Abstract

Chikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe a novel CHIKV infection model in zebrafish, where viral spread was live-imaged in the whole body up to cellular resolution. Infected cells emerged in various organs in one principal wave with a median appearance time of ∼14 hours post infection. Timing of infected cell death was organ dependent, leading to a shift of CHIKV localization towards the brain. As in mammals, CHIKV infection triggered a strong type-I interferon (IFN) response, critical for survival. IFN was mainly expressed by neutrophils and hepatocytes. Cell type specific ablation experiments further demonstrated that neutrophils play a crucial, unexpected role in CHIKV containment. Altogether, our results show that the zebrafish represents a novel valuable model to dynamically visualize replication, pathogenesis and host responses to a human virus.

Zebrafish: Modeling for Herpes Simplex Virus Infections

“…Some recent studies with human viruses also address that cell-and tissuespecific pathologies can be visualized with the zebrafish model. 23,[38][39][40][41] The future goal is to complement what we have learned in the mouse model and use genetic and embryological benefits of the zebrafish system to address human viral infections. There are multiple strengths in the zebrafish model, which can bring virologists, immunologists, and cell biologists together.…”

“…30,31,34,35 Although only few human viruses 21,[23][24][25][26][36][37][38][39] have been reported to infect zebrafish, the potential to take advantage of the zebrafish model is growing. There are several advantages of utilizing zebrafish to use microbial infections such as its small size, rapid breeding cycle, low maintenance cost offers large-scale infection analysis that can be very useful in defining infection requirements and confirming them in previously defined mammalian models 40,41 ( Table 3). Female zebrafish can be mated weekly and produce 100-200 progeny per clutch.…”

Characterization of samhd1 Morphant Zebrafish Recapitulates Features of the Human Type I Interferonopathy Aicardi-Goutières Syndrome

“…Brain hemorrhage analyses were performed on embryos harvested from a double transgenic (fli1a:GFP) y1 / (gata1a:DsRed) sd2 adult zebrafish cross (19,20), hereafter referred to as fli:GFP/gata1:DsRed. The (ifnphi1:mcherry) ip1 transgenic reporter line was used for ifnphi1 expression analyses (21). Fertilized embryos were collected and staged according to standard guidelines (22).…”

“…However, only IFN-w1 and IFN-w3 are functional during larval development (30). We took advantage of the transgenic ifnphi1:mCherry reporter line, embryos of which exhibit increased expression of mCherry in a subset of cells following viral infection, reflecting endogenous ifnphi1 expression (21). To determine whether the increase in expression of our putative immune gene panel in the samhd1 morphants was also associated with upregulation of ifnphi1 itself, we performed samhd1 knockdown experiments in zebrafish embryos harvested from the transgenic ifnphi1:mCherry reporter line.…”

Regard à travers le danio pour mieux comprendre les interactions hôte/pathogène

“…En effet, l'injection du CHIKV dans le poisson se caractérise par une infection cellulaire non spécifique et la formation d'un réser-voir viral dans le cerveau. Malgré une forte apoptose cellulaire, le déclenchement d'une importante réponse interféron par les neutrophiles conditionne la survie des embryons infectés [24].…”