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

Date Published: September 5, 2013

Publisher: Public Library of Science

Author(s): Nuno Palha, Florence Guivel-Benhassine, Valérie Briolat, Georges Lutfalla, Marion Sourisseau, Felix Ellett, Chieh-Huei Wang, Graham J. Lieschke, Philippe Herbomel, Olivier Schwartz, Jean-Pierre Levraud, Mark T. Heise.


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.

Partial Text

Chikungunya virus (CHIKV) is a mosquito-transmitted virus that causes serious illness and has reemerged in Africa and Asia since 2000, causing outbreaks with millions of cases after decades of near-absence [1]. The epidemic spread to previously CHIKV-free areas, such as La Reunion Island in the Indian Ocean, probably as a consequence of the adaptive mutation of the virus to a new vector species, Aedes albopictus, the tiger mosquito [2], [3], [4], [5]. Unlike traditional CHIKV vectors such as A. aegypti, A. albopictus can produce cold-resistant eggs and is a major invasive species of temperate countries [6], and as it also seems to better transmit the virus [7], CHIKV is now threatening to invade many new territories including the Caribbean, southeast USA and southern Europe. There is currently no commercial vaccine or efficient treatment available for this disease [1].

In this study, we establish zebrafish as a new model for the study of the pathogenesis of CHIKV. The overall course of viral spread in zebrafish larvae was close to that observed in mammals, with an early peak of viremia followed by a decline, similar targeted cell types, and a critical dependence on the host IFN response for the control of the virus. In addition, the powerful in vivo imaging techniques available in zebrafish revealed new features of the infection.




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