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.
Highlights
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]
Chikungunya, a re-emerging disease caused by a mosquito-transmitted virus, is an important public health problem
We developed a zebrafish model for chikungunya virus infection
Summary
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 CHIKVfree 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 seems to better transmit the virus [7], CHIKV is threatening to invade many new territories including the Caribbean, southeast USA and southern Europe. CHIKV infection is often debilitating and may last from weeks to months; its symptoms in humans include acute fever, rash, joint and muscle pain, chronic arthralgia and, more rarely, severe complications with a fatality rate of about 1 in 1000 [1,8,9,10]. Specific antibodies become detectable shortly after and contribute to virus clearance [11]
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