The effect of Zika virus infection in the ferret

Abstract

Although initial observations of infections with the Zika virus describe a mild illness, more recent reports show that infections by Zika result in neurotropism. In 2015, substantial congenital malformations were observed, with numerous infants born with microcephaly in Brazil. To study the underlying mechanism and effects of the disease, it is critical to find suitable animal models. Rodents lack an immune system parallel to humans and also have lissencephalic brains, which are likely to react differently to infections. As the smallest gyrencephalic mammal, ferrets may provide an important animal model to study the Zika virus, as their brains share many characteristics with humans. To evaluate the prospect of using ferrets to study Zika virus infection, we injected seven pregnant jills with the PR strain subcutaneously on gestational day 21, corresponding to the initiation of corticogenesis. These injections resulted in mixed effects. Two animals died of apparent infection, and all kits were resorbed in another animal that did not die. The other four animals remained pregnant until gestational day 40, when the kits were delivered by caesarian section. We evaluated the animals using CT, MRI, diffusion tensor imaging, and immunohistochemistry. The kits displayed a number of features compatible with an infection that impacted both the brain and skull. The outcomes, however, were variable and differed within and across litters, which ranged from the absence of observable abnormalities to prominent changes, suggesting differential vulnerability of kits to infection by the Zika virus or to subsequent mechanisms of neurodevelopmental disruption.

Fetal Rhesus Monkey First Trimester Zika Virus Infection Impacts Cortical Development in the Second and Third Trimesters

“…These findings are in line with reports showing that endothelial cells-a key component of developing vasculature in the fetal brain-also express the AXL receptor and are prime targets of infection (Richard et al 2017). Zika administration in gravid ferrets produced a similar increase in cortical vessel size in the embryonic ferret cortex (Hutchinson et al 2019), whereas studies in the mouse have reported a decrease in vascular density and vessel branching (Garcez et al 2018). These contrasting findings, particularly between embryonic mouse and fetal rhesus monkey, may represent species differences, contrasting patterns of vascular development between lissencephalic versus gyrencephalic cortices, and/or differences in methodology.…”

The Ferret as a Model System for Neocortex Development and Evolution

“…Since ferrets exhibit an expanded and folded neocortex, they are suitable for modeling diseases such as microcephaly ( Johnson et al, 2018 ) and lissencephaly ( Shinmyo et al, 2017 ). Considering the important role of ferrets in virology and immunology for modeling human influenzas, it is important to emphasize the role of ferrets for studying the neurotropic effects of viruses such as Zika ( Hutchinson et al, 2019 ) and SARS-CoV-2. Combining the previous application in neurodevelopmental disorders and viral infections, the ferret is becoming an emerging model organism for studying the relationship between the maternal immune activation and neuropsychiatric diseases ( Li et al, 2018 ).…”

“…Recently, the ferret has been used in research involving infection by Zika virus due to the similarity of both the immune responses and certain neurodevelopmental features with those of human, referred to earlier in this review ( Hutchinson et al, 2019 ). Zika virus is neurotropic and an infection during pregnancy in humans can lead to neurodevelopmental malformations, such as microcephaly, i.e.…”

“…reduced brain size. In ferret these phenotypes were recapitulated with a high variability among embryos suggesting that the ferret can be used as a valuable model to understand the mechanism of the Zika pathology that can lead to a heterogeneous magnitude of symptoms ( Hutchinson et al, 2019 ).…”

Chemical composition and larvicidal activity against Aedes mosquitoes of essential oils from Arisaema fargesii

“…Zika virus affects the brain during development and can result in severe neurologic impairments. The infection of Zika virus during pregnancy may cause fetal malformations . Aedes aegypti Linn, the principal vector of dengue virus, originated in Africa, but is now found throughout the world in tropical and subtropical regions .…”