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Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
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Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

Hanxia Huang1, Barry Falgout1, Kazuyo Takeda1

  • 1Food and Drug Administration, Silver Spring, MD, United States.

Virology
|January 10, 2017
PubMed

Insights

Hemin reduces Zika virus (ZIKV) replication in human macrophages by inducing heme oxygenase-1 (HO-1). This innate cellular response offers a potential therapeutic strategy against ZIKV infection with minimal toxicity.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Zika virus (ZIKV) poses a significant public health threat.
  • Monocyte-derived macrophages (MDM) are identified as susceptible cells for ZIKV infection.
  • Understanding cellular mechanisms to control ZIKV replication is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the potential of hemin and its downstream effects in controlling ZIKV replication.
  • To elucidate the role of heme oxygenase-1 (HO-1) and nuclear factor erythroid-related factor 2 (Nrf2) in ZIKV infection.

Main Methods:

  • In vitro infection of LLC-MK2 cells and primary human monocyte-derived macrophages (MDM) with ZIKV.
  • Treatment with hemin to induce heme oxygenase-1 (HO-1) expression.
  • Silencing of HO-1 and Nrf2 genes using RNA interference.
  • Quantification of ZIKV replication and assessment of cellular toxicity.

Main Results:

  • Hemin treatment significantly reduced ZIKV replication by over 90% in both cell types.
  • Hemin induced HO-1 expression, which correlated with decreased ZIKV replication.
  • Silencing HO-1 or Nrf2 diminished the hemin-mediated suppression of ZIKV.
  • Hemin treatment showed minimal toxicity to the infected cells.

Conclusions:

  • Hemin effectively inhibits ZIKV replication in macrophages through the induction of HO-1 and Nrf2.
  • Stimulation of this innate cellular pathway presents a promising therapeutic avenue for ZIKV infection.
  • The findings suggest a novel host-directed strategy against ZIKV.
Keywords:
Heme oxygenase-1MacrophagesMonocytesNuclear factor erythroid-related factor 2Zika

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