PUBLICATION
Influenza a virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment
- Authors
- Gabor, K.A., Goody, M.F., Mowel, W.K., Breitbach, M.E., Gratacap, R.L., Witten, P.E., Kim, C.H.
- ID
- ZDB-PUB-140906-4
- Date
- 2014
- Source
- Disease models & mechanisms 7(11): 1227-37 (Journal)
- Registered Authors
- Kim, Carol H., Witten, P. Eckhard
- Keywords
- Influenza, Zebrafish, Virus, Innate immunity
- MeSH Terms
-
- Animals
- Antiviral Agents/therapeutic use*
- Disease Models, Animal*
- Humans
- Influenza A virus/isolation & purification*
- Influenza A virus/physiology
- Influenza, Human/drug therapy
- Influenza, Human/virology*
- Virus Replication
- Zebrafish/embryology
- PubMed
- 25190709 Full text @ Dis. Model. Mech.
Citation
Gabor, K.A., Goody, M.F., Mowel, W.K., Breitbach, M.E., Gratacap, R.L., Witten, P.E., Kim, C.H. (2014) Influenza a virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment. Disease models & mechanisms. 7(11):1227-37.
Abstract
Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in significant morbidity, mortality, and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains, and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis and host response to influenza infection, and for screening antiviral compounds. However, the current animal models used for influenza research are not amenable to visualization of host-pathogen interactions or high throughput drug screening. The zebrafish is widely recognized as a valuable model system for infectious disease research and therapeutic drug testing. Here, we describe a zebrafish model for human influenza A virus (IAV) infection and show that zebrafish embryos are susceptible to challenge with both influenza A strains APR8 and X-31 (Aichi). Influenza-infected zebrafish show an increase in viral burden and mortality over time. The expression of innate antiviral genes, gross pathology, and histopathology in infected zebrafish recapitulate clinical symptoms of influenza infections in humans. Zebrafish embryos were infected with a fluorescent reporter strain of IAV and, for the first time, influenza infection was visualized in a live vertebrate host, revealing a pattern of vascular endothelial infection. Treatment of infected zebrafish with a known anti-influenza compound, zanamivir, reduced mortality and expression of a fluorescent viral gene product, demonstrating the validity of this model to screen for potential antivirals. The zebrafish model system has provided invaluable insights into host-pathogen interactions for a range of infectious diseases. Here, we demonstrate a novel use of this species for IAV research. This model has great potential to advance our understanding of influenza infection and the associated host innate immune response.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping