A Porcine Model of Zika Virus Infection to Profile the In Utero Interferon Alpha Response

Methods Mol Biol. 2020:2142:181-195. doi: 10.1007/978-1-0716-0581-3_15.

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.

Keywords: Animal model; Fetus; In utero infection; Interferon; Pig; Zika virus.

Publication types

  • Video-Audio Media

MeSH terms

  • Amniotic Fluid / metabolism
  • Animals
  • Blood Chemical Analysis / methods
  • Blood Chemical Analysis / veterinary
  • Disease Models, Animal*
  • Female
  • Fetal Blood / metabolism
  • Fetal Diseases* / diagnostic imaging
  • Fetal Diseases* / metabolism
  • Fetal Diseases* / pathology
  • Fetal Diseases* / virology
  • Fetoscopy / methods
  • Fetoscopy / veterinary
  • Injections
  • Interferon-alpha / analysis
  • Interferon-alpha / blood
  • Interferon-alpha / metabolism*
  • Pregnancy
  • Pregnancy Complications, Infectious* / diagnostic imaging
  • Pregnancy Complications, Infectious* / metabolism
  • Pregnancy Complications, Infectious* / pathology
  • Swine*
  • Ultrasonography, Interventional / methods
  • Ultrasonography, Interventional / veterinary
  • Ultrasonography, Prenatal / methods
  • Ultrasonography, Prenatal / veterinary
  • Zika Virus / physiology
  • Zika Virus Infection* / diagnostic imaging
  • Zika Virus Infection* / metabolism
  • Zika Virus Infection* / pathology

Substances

  • Interferon-alpha