通过血红素加氧酶-1由Nrf2依赖性诱导的先天性宿主防御可抑制寨卡病毒复制。
Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication.
作者信息
Huang Hanxia, Falgout Barry, Takeda Kazuyo, Yamada Kenneth M, Dhawan Subhash
机构信息
Food and Drug Administration, Silver Spring, MD, United States.
National Institutes of Health, Bethesda, MD, United States.
出版信息
Virology. 2017 Mar;503:1-5. doi: 10.1016/j.virol.2016.12.019. Epub 2017 Jan 6.
Abstract
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.
摘要
我们确定原代人单核细胞衍生的巨噬细胞（MDM）是寨卡病毒（ZIKV）感染的易感靶细胞。我们证明血红素（血红素分解代谢酶血红素加氧酶-1（HO-1）的天然诱导剂）在体外减少ZIKV复制方面具有显著作用。LLC-MK2猴肾细胞和原代MDM均表现出血红素诱导的HO-1表达，ZIKV复制大幅减少>90%，且对感染细胞几乎没有毒性。沉默HO-1或其上游调节基因核因子红细胞相关因子2（Nrf2）的表达，减弱了血红素诱导的对ZIKV感染的抑制作用，表明诱导这些细胞内介质在延缓ZIKV复制中起重要作用。血红素诱导的HO-1水平与ZIKV复制之间的负相关关系，基于刺激针对寨卡病毒感染的先天性细胞反应，提供了一种潜在有用的治疗方式。
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