Real-time whole-body visualization of Chikungunya Virus infection and host interferon response in zebrafish

PLoS Pathog. 2013;9(9):e1003619. doi: 10.1371/journal.ppat.1003619. Epub 2013 Sep 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / metabolism*
  • Alphavirus Infections / pathology*
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Brain / virology
  • Cell Line
  • Chikungunya Fever
  • Chikungunya virus / metabolism*
  • Cricetinae
  • Disease Models, Animal
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Hepatocytes / virology
  • Humans
  • Interferon Type I / biosynthesis*
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Neutrophils / virology
  • Organ Specificity
  • Zebrafish Proteins / biosynthesis*

Substances

  • Interferon Type I
  • Zebrafish Proteins

Grant support

This work was financed by the Agence Nationale de la Recherche (Zebraflam grant ANR-10-MIDI-009, and CHIK-HOST-PATH2 grant), Region Ile-de-France (DIM-Malinf), and institutional grants from the Institut Pasteur and CNRS. NP is endowed with a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BD/60678/2009). GJL is supported by the National Health and Medical Research Council (grants 461208 and 637394). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.