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

PLoS Pathogens

Graham J. Lieschke¹  Florence Guivel-Benhassine²  Chieh-Huei Wang²  Marion Sourisseau³  Jean-Pierre Levraud³  Nuno Palha⁴  Felix Ellett⁴  Olivier Schwartz⁵  Georges Lutfalla⁵  Philippe Herbomel⁶  Valérie Briolat⁷ 

[1] CNRS UMR5235, Dynamiques des Interactions Membranaires et Pathologiques, Montpellier, France;CNRS URA2578, Paris, France;CNRS URA3015, Paris, France;Institut Pasteur, Macrophages et Développement de l'Immunité, Department of Developmental and Stem Cells Biology, Paris, France;Institut Pasteur, Virus et Immunité, Department of Virology, Paris, France;Université Montpellier II, Montpellier, France;Université Pierre et Marie Curie, Paris, France

关键词: Chikungunya infection;    Zebrafish;    Neutrophils;    Chikungunya virus;    Larvae;    White blood cells;    Hepatocytes;    Macrophages;   

DOI  :  10.1371/journal.ppat.1003619

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY