Abstract
Pigs are highly relevant to model human in utero Zika virus (ZIKV) infection because both species have similar physiology, genetics, immunity, fetal brain development, and postnatal brain growth. The virus causes persistent in utero infection and replicates in the fetal brain, fetal membranes, and placenta. Subclinical persistent in utero infection in mid-gestation also increases interferon alpha (IFN-α) levels in fetal blood plasma and amniotic fluid. Moreover, we demonstrated altered IFN-α responses in porcine offspring affected with subclinical in utero ZIKV infection. Elevated levels of in utero type I interferons were suggested to play a role in fetal pathology. Thus, the porcine model may provide an understanding of ZIKV-induced immunopathology in fetuses and sequelae in offspring, which is important for the development of targeted interventions. Here, we describe surgery, ultrasound-guided in utero injection, postoperative monitoring, sampling, and cytokine testing protocols.
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Acknowledgments
We thank VIDO-InterVac animal care technicians and veterinarians for the help with animal experiments. ZIKV was provided by the Division of Vector-Borne Diseases, Centers for Disease Control and Prevention (Fort Collins, Colorado, USA). Jan Erickson made drawings in Figs. 1 and 2. Published as VIDO-InterVac manuscript series number 875.
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1 Electronic Supplementary Material
Ultrasound-guided fetal inoculation. To confirm fetal viability, fetal heart beating is verified prior to and after injection. (IC) Intracerebral injection. (IP) Intraperitoneal injection. (IA) Intraamniotic injection. The video footage is slowed down (1.5×) for better perception. (MP4 11366 kb)
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Trus, I., Walker, S., Fuchs, M., Udenze, D., Gerdts, V., Karniychuk, U. (2020). A Porcine Model of Zika Virus Infection to Profile the In Utero Interferon Alpha Response. In: Kobinger, G., Racine, T. (eds) Zika Virus. Methods in Molecular Biology, vol 2142. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0581-3_15
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DOI: https://doi.org/10.1007/978-1-0716-0581-3_15
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