Recapitulation of Retinal Damage in Zebrafish Larvae Infected with Zika Virus

Abstract

Zebrafish are increasingly being utilized as a model to investigate infectious diseases and to advance the understanding of pathogen–host interactions. Here, we take advantage of the zebrafish to recapitulate congenital ZIKV infection and, for the first time, demonstrate that it can be used to model infection and reinfection and monitor anti-viral and inflammatory immune responses, as well as brain growth and eye abnormalities during embryonic development. By injecting a Brazilian strain of ZIKV into the yolk sac of one-cell stage embryos, we confirmed that, after 72 h, ZIKV successfully infected larvae, and the physical condition of the virus-infected hosts included gross morphological changes in surviving embryos (84%), with a reduction in larval head size and retinal damage characterized by increased thickness of the lens and inner nuclear layer. Changes in locomotor activity and the inability to perceive visual stimuli are a result of changes in retinal morphology caused by ZIKV. Furthermore, we demonstrated the ability of ZIKV to replicate in zebrafish larvae and infect new healthy larvae, impairing their visual and neurological functions. These data reinforce the deleterious activity of ZIKV in the brain and visual structures and establish the zebrafish as a model to study the molecular mechanisms involved in the pathology of the virus.

Zebrafish—A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers

“…Zebrafish have also been effectively utilized to model neurodegenerative diseases [56], behavioral disorders [57,58], neuromuscular disorders [59][60][61][62][63], aging-related disorders [64][65][66], hematopoietic disorders [67][68][69][70], renal diseases [71][72][73][74], liver diseases [74][75][76][77], and eye diseases [78][79][80][81], to mention a few. In recent years, zebrafish have also been used to study infectious viral diseases, such as Zika [82] and COVID-19 [83].…”

Managing the Welfare of Zebrafish in Laboratory: Overview of Prevailing Diseases and Health Issues

“…Health management in zebrafish laboratories is mandatory since this model system becomes strikingly important to biomedical sciences in both larvae and adult stages [55]. Although several mammalian viral infections are modeled in zebrafish [56], naturally occurring infections are scarcely studied in zebrafish [57].…”

An Overview towards Zebrafish Larvae as a Model for Ocular Diseases

“…Recently, we recapitulated for the first time ZIKV infection using zebrafish embryos and larvae, especially the ability of ZIKV to infect head and eye structures during embryonic development, leading to developmental changes characterized by a reduction in head size and increased thickness of the retinal cell layers with consequent impairment of neurological and visual functions [ 115 ]. Toxoplasma gondii tachyzoites were demonstrated to infect cardiac myocytes, liver, spleen, brain, ovaries, pancreas, kidney and skeletal muscles, gills, and eyes of adult zebrafish; clinical signs presented in these fish included bilateral exopthalmia [ 116 ].…”