Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment
| Autor: | Kristin A. Gabor, Walter K. Mowel, Carol H. Kim, Michelle F. Goody, P. Eckhard Witten, Remi L. Gratacap, Meghan E. Breitbach |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Medicine (miscellaneous)
lcsh:Medicine medicine.disease_cause Virus Replication Immunology and Microbiology (miscellaneous) Pandemic Influenza A virus Zebrafish NECROSIS VIRUS GENE-EXPRESSION Innate immunity 0303 health sciences DANIO-RERIO biology POLYSIALIC ACID 030302 biochemistry & molecular biology Influenza research HUMAN-DISEASE 3. Good health Virus Viral load medicine.drug Research Article lcsh:RB1-214 Neuroscience (miscellaneous) Antiviral Agents General Biochemistry Genetics and Molecular Biology FREE CLICK CHEMISTRY 03 medical and health sciences Zanamivir Influenza Human medicine lcsh:Pathology Animals Humans 030304 developmental biology lcsh:R Biology and Life Sciences biology.organism_classification Virology NERVOUS-SYSTEM Influenza MODEL Disease Models Animal TRANSGENIC ZEBRAFISH Infectious disease (medical specialty) Immunology RESPONSES |
| Zdroj: | Disease Models & Mechanisms, Vol 7, Iss 11, Pp 1227-1237 (2014) Disease Models & Mechanisms DISEASE MODELS & MECHANISMS |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial 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 of 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, the gross pathology and the histopathology in infected zebrafish recapitulate clinical symptoms of influenza infections in humans. This is the first time that zebrafish embryos have been infected with a fluorescent IAV in order to visualize infection 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 the expression of a fluorescent viral gene product, demonstrating the validity of this model to screen for potential antiviral drugs. 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. |
| Databáze: | OpenAIRE |
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