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Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits
Zika virus replication
#MMPMID28068513
Huang H
; Falgout B
; Takeda K
; Yamada KM
; Dhawan S
Virology
2017[Mar]; 503
(?): 1-5
PMID28068513
show ga
We identified primary human monocyte-derived macrophages (MDM) as vulnerable
target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of
hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1),
in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells
and primary MDM exhibited hemin-induced HO-1 expression with major reductions of
>90% in ZIKV replication, with little toxicity to infected cells. Silencing
expression of HO-1 or its upstream regulatory gene, nuclear factor
erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV
infection, suggesting an important role for induction of these intracellular
mediators in retarding ZIKV replication. The inverse correlation between
hemin-induced HO-1 levels and ZIKV replication provides a potentially useful
therapeutic modality based on stimulation of an innate cellular response against
Zika virus infection.
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