Abstract:Naturally occurring viral infections have the potential to introduce confounding variability that leads to invalid and misinterpreted data. Whereas the viral diseases of research rodents are well characterized and closely monitored, no naturally occurring viral infections have been characterized for the laboratory zebrafish (Danio rerio), an increasingly important biomedical research model. Despite the ignorance about naturally occurring zebrafish viruses, zebrafish models are rapidly expanding in areas of bio… Show more
“…Some recent studies with human viruses also address that cell-and tissuespecific pathologies can be visualized with the zebrafish model. 23,[38][39][40][41] The future goal is to complement what we have learned in the mouse model and use genetic and embryological benefits of the zebrafish system to address human viral infections. There are multiple strengths in the zebrafish model, which can bring virologists, immunologists, and cell biologists together.…”
Section: Discussionmentioning
confidence: 99%
“…30,31,34,35 Although only few human viruses 21,[23][24][25][26][36][37][38][39] have been reported to infect zebrafish, the potential to take advantage of the zebrafish model is growing. There are several advantages of utilizing zebrafish to use microbial infections such as its small size, rapid breeding cycle, low maintenance cost offers large-scale infection analysis that can be very useful in defining infection requirements and confirming them in previously defined mammalian models 40,41 ( Table 3).…”
Section: Zebrafish Model: Overall Advantages To Study Viral Infectionsmentioning
For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.
“…Some recent studies with human viruses also address that cell-and tissuespecific pathologies can be visualized with the zebrafish model. 23,[38][39][40][41] The future goal is to complement what we have learned in the mouse model and use genetic and embryological benefits of the zebrafish system to address human viral infections. There are multiple strengths in the zebrafish model, which can bring virologists, immunologists, and cell biologists together.…”
Section: Discussionmentioning
confidence: 99%
“…30,31,34,35 Although only few human viruses 21,[23][24][25][26][36][37][38][39] have been reported to infect zebrafish, the potential to take advantage of the zebrafish model is growing. There are several advantages of utilizing zebrafish to use microbial infections such as its small size, rapid breeding cycle, low maintenance cost offers large-scale infection analysis that can be very useful in defining infection requirements and confirming them in previously defined mammalian models 40,41 ( Table 3).…”
Section: Zebrafish Model: Overall Advantages To Study Viral Infectionsmentioning
For many years, zebrafish have been the prototypical model for studies in developmental biology. In recent years, zebrafish has emerged as a powerful model system to study infectious diseases, including viral infections. Experiments conducted with herpes simplex virus type-1 in adult zebrafish or in embryo models are encouraging as they establish proof of concept with viral-host tropism and possible screening of antiviral compounds. In addition, the presence of human homologs of viral entry receptors in zebrafish such as 3-O sulfated heparan sulfate, nectins, and tumor necrosis factor receptor superfamily member 14-like receptor bring strong rationale for virologists to test their in vivo significance in viral entry in a zebrafish model and compare the structure-function basis of virus zebrafish receptor interaction for viral entry. On the other end, a zebrafish model is already being used for studying inflammation and angiogenesis, with or without genetic manipulations, and therefore can be exploited to study viral infection-associated pathologies. The major advantage with zebrafish is low cost, easy breeding and maintenance, rapid lifecycle, and a transparent nature, which allows visualizing dissemination of fluorescently labeled virus infection in real time either at a localized region or the whole body. Further, the availability of multiple transgenic lines that express fluorescently tagged immune cells for in vivo imaging of virus infected animals is extremely attractive. In addition, a fully developed immune system and potential for receptor-specific knockouts further advocate the use of zebrafish as a new tool to study viral infections. In this review, we focus on expanding the potential of zebrafish model system in understanding human infectious diseases and future benefits.
“…No naturally occurring viral infections have been characterized for zebrafish (10). Moreover, the experimental susceptibility of zebrafish to viral infections has been demonstrated with other fish viruses (11)(12)(13) and also with mammalian viruses (14)(15)(16).…”
Section: Pathogenic Mechanisms Of Hemorrhagic Viruses Are Diverse Anmentioning
Hemorrhagic viral diseases are distributed worldwide with important pathogens, such as dengue virus or hantaviruses. The lack of adequate in vivo infection models has limited the research on viral pathogenesis and the current understanding of the underlying infection mechanisms. Although hemorrhages have been associated with the infection of endothelial cells, other cellular types could be the main targets for hemorrhagic viruses. Our objective was to take advantage of the use of zebrafish larvae in the study of viral hemorrhagic diseases, focusing on the interaction between viruses and host cells. Cellular processes, such as transendothelial migration of leukocytes, virus-induced pyroptosis of macrophages. and interleukin-1 (Il-1) release, could be observed in individual cells, providing a deeper knowledge of the immune mechanisms implicated in the disease. Furthermore, the application of these techniques to other pathogens will improve the current knowledge of host-pathogen interactions and increase the potential for the discovery of new therapeutic targets.
IMPORTANCEPathogenic mechanisms of hemorrhagic viruses are diverse, and most of the research regarding interactions between viruses and host cells has been performed in cell lines that might not be major targets during natural infections. Thus, viral pathogenesis research has been limited because of the lack of adequate in vivo infection models. The understanding of the relative pathogenic roles of the viral agent and the host response to the infection is crucial. This will be facilitated by the establishment of in vivo infection models using organisms such as zebrafish, which allows the study of the diseases in the context of a complete individual. The use of this animal model with other pathogens could improve the current knowledge on host-pathogen interactions and increase the potential for the discovery of new therapeutic targets against diverse viral diseases.
“…59 Multiple endogenous retroviruses, retrotransposons, and retroid agent sequences have been described in the zebrafish genome 60,61 ; however, production of an infectious virion has not been reported. There is a single brief report of a naturally occurring infection of zebrafish by Red-spotted grouper nervous necrosis virus, a Betanodavirus.…”
The presence of subclinical infection or clinical disease in laboratory zebrafish may have a significant impact on research results, animal health and welfare, and transfer of animals between institutions. As use of zebrafish as a model of disease increases, a harmonized method for monitoring and reporting the health status of animals will facilitate the transfer of animals, allow institutions to exclude diseases that may negatively impact their research programs, and improve animal health and welfare. All zebrafish facilities should implement a health monitoring program. In this study, we review important aspects of a health monitoring program, including choice of agents, samples for testing, available testing methodologies, housing and husbandry, cost, test subjects, and a harmonized method for reporting results. Facilities may use these recommendations to implement their own health monitoring program.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.