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Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
09:11

Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons

Published on: August 23, 2016

20.9K

Type I interferon receptor (IFNAR2) deficiency reveals Zika virus cytopathicity in human macrophages and microglia

Aidan T Hanrath1,2, Catherine F Hatton1,2, Florian Gothe1

  • 1Immunology and Inflammation Theme, Translational and Clinical Research Institute, Newcastle University, Newcastle, United Kingdom.

Frontiers in Immunology
|November 28, 2022
PubMed

Insights

Type I interferons (IFN-I) normally control Zika virus (ZIKV) replication in macrophages. Disrupting IFN-I signaling paradoxically enhances ZIKV replication and cell death, revealing its pathogenic role.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Macrophages are primary targets for Zika virus (ZIKV) infection, potentially serving as viral reservoirs.
  • ZIKV infection in macrophages triggers type I interferons (IFN-I), crucial antiviral cytokines with complex roles in pathogenesis.
  • The ability of macrophages to support ZIKV replication without cell death is not fully understood.

Purpose of the Study:

  • To investigate the functional role of the IFN-I response in ZIKV infection of human macrophages.
  • To determine if IFN-I signaling is essential for controlling ZIKV replication and cytopathicity in macrophages.

Main Methods:

  • Generated human induced pluripotent stem cell (iPSC)-derived macrophages from a patient with a complete deficiency of IFNAR2, the IFN-I receptor subunit.
  • Assessed ZIKV replication and cell death in IFNAR2-deficient iPS-macrophages.
  • Confirmed findings by genetically and pharmacologically inhibiting IFN-I signaling in control iPS-macrophages and iPS-microglia.

Main Results:

  • IFNAR2-deficient iPS-macrophages exhibited profoundly defective IFN-I signaling.
  • These cells showed significantly enhanced ZIKV replication and increased cell death compared to controls.
  • Inhibition of IFN-I signaling in control cells recapitulated these findings, demonstrating ZIKV's inherent cytopathicity towards macrophages.
  • These effects were also observed in iPS-microglia.

Conclusions:

  • The capacity of macrophages to sustain ZIKV replication without causing cell death is dependent on the balance of IFN-I signaling.
  • IFN-I signaling is critical for controlling ZIKV replication and preventing cytopathic effects in macrophages.
  • Innate antiviral responses, specifically IFN-I, may paradoxically contribute to ZIKV persistence and pathogenesis by maintaining viral reservoirs.
Keywords:
IFNAR2 deficiencyZika virusantiviral statecell deathinborn errors of immunityinterferon-stimulated genesmacrophagestype I interferons

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