Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment

Gabor, Kristin A.; Goody, Michelle F.; Mowel, Walter K.; Breitbach, Meghan E.; Gratacap, Remi L.; Witten, P. Eckhard; Kim, Carol H.

doi:10.1242/dmm.014746

Cited by 72 publications

(85 citation statements)

References 58 publications

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“…Many zebrafish models for virus infection and immunity have been recently described (Gabor et al, 2014) and comprehensively reviewed (Levraud et al, 2014). These valuable models can be used to investigate the functions of genes in different pathogenic interactions, either through the use of morpholino knockdown in embryos, stable knockout lines, or transgenic lines, such as the dominant-negative model described herein.…”

Section: Discussionmentioning

confidence: 99%

“…The zebrafish ( Danio rerio ) model has provided novel insights into pathogenesis (Allen and Neely, 2010; Briolat et al, 2014; Gabor et al, 2014; Ludwig et al, 2011; Meijer and Spaink, 2011; Phelan et al, 2005b; Ramakrishnan; Sullivan and Kim, 2008; Tobin and Ramakrishnan, 2008; Yakoub et al, 2014; Zou et al, 2014b). Recently, a zebrafish MDA5 homolog and splice variant were described as transcriptionally induced upon virus infection and capable of conferring viral resistance when overexpressed in vitro (Zou et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

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A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

Gabor

Charette

Pietraszewski

et al. 2015

Developmental & Comparative Immunology

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Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

Gabor

Charette

Pietraszewski

et al. 2015

Developmental & Comparative Immunology

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“…We recently developed the first microinjection mucosal infection model in the zebrafish larva, and it has been used to study sterile inflammation and infection with both viral and fungal pathogens (27)(28)(29). In this study, we leveraged this infection model to achieve a high spatiotemporal resolution of neutrophil-C. albicans dynamics at the mucosal level.…”

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confidence: 99%

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

2017

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Candida albicans is a ubiquitous mucosal commensal that is normally prevented from causing acute or chronic invasive disease. Neutrophils contribute to protection in oral infection but exacerbate vulvovaginal candidiasis. To dissect the role of neutrophils during mucosal candidiasis, we took advantage of a new, transparent zebrafish swim bladder infection model. Intravital microscopic tracking of individual animals revealed that the blocking of neutrophil recruitment leads to rapid mortality in this model through faster disease progression. Conversely, artificial recruitment of neutrophils during early infection reduces disease pressure. Noninvasive longitudinal tracking showed that mortality is a consequence of C. albicans breaching the epithelial barrier and invading surrounding tissues. Accordingly, we found that a hyperfilamentous C. albicans strain breaches the epithelial barrier more frequently and causes mortality in immunocompetent zebrafish. A lack of neutrophils at the infection site is associated with less fungusassociated extracellular DNA and less damage to fungal filaments, suggesting that neutrophil extracellular traps help to protect the epithelial barrier from C. albicans breach. We propose a homeostatic model where C. albicans disease pressure is balanced by neutrophil-mediated damage of fungi, maintaining this organism as a commensal while minimizing the risk of damage to host tissue. The unequaled ability to dissect infection dynamics at a high spatiotemporal resolution makes this zebrafish model a unique tool for understanding mucosal host-pathogen interactions.KEYWORDS Candida albicans, mucosal immunity, neutrophils, zebrafish C andida albicans is the most successful commensal fungus at causing opportunistic mucosal and invasive infections (1, 2). The opportunistic nature of C. albicans mucosal infection suggests that there is a constantly challenged impasse between our immune defenses and C. albicans virulence factors (3, 4). Chronic mucocutaneous candidiasis (CMC) is associated with inborn errors of adaptive immune pathways, especially Th17 immunity (5). However, acute oropharyngeal candidiasis (OPC) is more common in neutropenic patients and can result from a multitude of immunesuppressive treatments that affect both innate and adaptive immunity, such as radiation/chemotherapy and corticosteroid or antibiotic use (6, 7).Experimental work in murine models of OPC suggests that C. albicans is kept at bay in mucosal tissues through the action of epithelial cells, neutrophils, and macrophages (8). To protect from mucosal invasion in OPC, neutrophils must be present in the blood, be recruited to the site of infection, and possess a fully functional antimicrobial arsenal (9-12). Neutrophils attack both the yeast and filamentous forms of C. albicans and are associated with vulvovaginal candidiasis (13-15). Counterintuitively, because symptomatic infection is more closely associated with high neutrophil numbers than with the fungal burden, it is believed that neutrophils do more to cause...

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“…Zebrafish models based on gene misexpression tp53 zdf1/zdf1 ; Tg(mitfa:Hsa.BRAF_V600E) czt13Tg [ZDB-FISH-150901-14943]Standard conditions [ZECO:0000103]Melanoma (Yen et al 2013) [DOID:1909] Tg(mitfa:mitfa), Tg(rag2:Hsa.MYC-ERT2) zdf14Tg ; Tg(lck:lck-EGFP) cz2Tg [ZDB-FISH-150901-17819]Standard conditions [ZECO:0000103]Acute T cell leukemia (Ridges et al 2012) [DOID:5603] Tg(spi1b:LOXP-EGFP-LOXP-Hsa.NUP98-Hsa.HOXA9) hsi1Tg ; Tg(hsp70l:Cre) zdf13Tg [ZDB-FISH-150901-25078]Heat shock [ZECO:0000166]Myeloid leukemia (Forrester et al 2011) [DOID:8692] Tg(fabp10a:edn1,myl7:EGFP) nn1005Tg [ZDB-FISH-150901-2358]Standard conditions [ZECO:0000103]Hepatocellular carcinoma (Lu et al 2014) [DOID:684]C. Zebrafish models based on exposure to disease causing conditions AB [ZDB-GENO-960809-7]Chemical treatment: ethanol [ZECO:0000111: CHEBI:16236]Fetal alcohol spectrum disorders (Fernandes et al 2015) [DOID:0050696]WT [ZDB-GENO-030619-2]Increased food availability [ZECO:0000247]Obesity (Montalbano et al 2015) [DOID:9970]WT [ZDB-GENO-030619-2]Bacterial treatment: Mycobacterium marinum [ZECO:0000106: NCBITaxon:1781]Tuberculosis (Sridevi et al 2014) [DOID:399] mitfa w2/w2 ; roy a9/a9 [ZDB-FISH-150901-6638]Viral treatment: influenza virus [ZECO:0000110: NCBITaxon:11309]Influenza (Gabor et al 2014) [DOID:8469]D. Zebrafish models based on disease phenotype similarities TU [ZDB-GENO-990623-3]Chemical treatment: pentetrazol [ZECO:0000111: CHEBI:34910]Epilepsy (Siebel et al 2015) [DOID:1826]WT [ZDB-GENO-030619-2]Chemical treatment: oxidopamine [ZECO:0000111: CHEBI:78741]Parkinson’s disease (Panula et al 2006) [DOID:14330]WT [ZDB-GENO-030619-2]Chemical treatment: N-methyl-4-phenylpyridinium [ZECO:0000111: CHEBI:641] Tg(ins:CFP-NTR) s892Tg [ZDB-FISH-150901-27537]Chemical ablation: insulin secreting cell [ZECO:0000169: ZFA:0009101], chemical treatment: metronidazole [ZECO:0000111: CHEBI:6909]Type 1 diabetes mellitus (Tsuji et al 2014<...>…”

Section: Zfin As a Resource For Zebrafish Translational Researchmentioning

confidence: 99%

“…For example, bacterial or viral infectious diseases, like tuberculosis or influenza, can be modeled in zebrafish that have been infected with the disease-causing bacteria or viruses (Table 1C; Gabor et al 2014; Sridevi et al 2014). Zebrafish embryos exposed to ethanol have been used as models of fetal alcohol spectrum disorders, which result from maternal alcohol consumption during pregnancy (Table 1C).…”

Section: Zfin As a Resource For Zebrafish Translational Researchmentioning

confidence: 99%

Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN

et al. 2017

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The Zebrafish Model Organism Database (ZFIN; https://zfin.org) is the central resource for genetic, genomic, and phenotypic data for zebrafish (Danio rerio) research. ZFIN continuously assesses trends in zebrafish research, adding new data types and providing data repositories and tools that members of the research community can use to navigate data. The many research advantages and flexibility of manipulation of zebrafish have made them an increasingly attractive animal to model and study human disease.To facilitate disease-related research, ZFIN developed support to provide human disease information as well as annotation of zebrafish models of human disease. Human disease term pages at ZFIN provide information about disease names, synonyms, and references to other databases as well as a list of publications reporting studies of human diseases in which zebrafish were used. Zebrafish orthologs of human genes that are implicated in human disease etiology are routinely studied to provide an understanding of the molecular basis of disease. Therefore, a list of human genes involved in the disease with their corresponding zebrafish ortholog is displayed on the disease page, with links to additional information regarding the genes and existing mutations. Studying human disease often requires the use of models that recapitulate some or all of the pathologies observed in human diseases. Access to information regarding existing and published models can be critical, because they provide a tractable way to gain insight into the phenotypic outcomes of the disease. ZFIN annotates zebrafish models of human disease and supports retrieval of these published models by listing zebrafish models on the disease term page as well as by providing search interfaces and data download files to access the data. The improvements ZFIN has made to annotate, display, and search data related to human disease, especially zebrafish models for disease and disease-associated gene information, should be helpful to researchers and clinicians considering the use of zebrafish to study human disease.

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Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment

Cited by 72 publications

References 58 publications

A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance

Control of Mucosal Candidiasis in the Zebrafish Swim Bladder Depends on Neutrophils That Block Filament Invasion and Drive Extracellular-Trap Production

Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN

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