Therapeutic potential of the heme oxygenase-1 inducer hemin against Ebola virus infection.

Q4 Medicine Current Trends in Immunology Pub Date : 2016-01-01

Hanxia Huang, Krishnamurthy Konduru, Veronica Solovena, Zhao-Hua Zhou, Namita Kumari, Kazuyo Takeda, Sergei Nekhai, Sina Bavari, Gerardo G Kaplan, Kenneth M Yamada, Subhash Dhawan

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Abstract

Promising drugs to treat Ebola virus (EBOV) infection are currently being developed, but so far none has shown efficacy in clinical trials. Drugs that can stimulate host innate defense responses may retard the progression of EBOV disease. We report here the dramatic effect of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of EBOV replication. Treatment of primary monocyte-derived macrophages (MDM), Vero E6 cells, HeLa cells, and human foreskin fibroblasts (HFF1) with hemin reduced EBOV infection by >90%, and showed minimal toxicity to infected cells. Inhibition of HO-1 enzymatic activity and silencing HO-1 expression prevented the hemin-mediated suppression of EBOV infection, suggesting an important role for induction of this intracellular mediator in restricting EBOV replication. The inverse correlation between hemin-induced HO-1 and EBOV replication provides a potentially useful therapeutic modality based on the stimulation of an innate cellular response against Ebola infection.

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血红素加氧酶-1 诱导剂血红素对埃博拉病毒感染的治疗潜力。

目前正在开发治疗埃博拉病毒（EBOV）感染的药物，但迄今为止，还没有一种药物在临床试验中显示出疗效。能够刺激宿主先天防御反应的药物可能会延缓埃博拉病毒疾病的发展。我们在此报告了血红素（血红素分解酶血红素加氧酶-1（HO-1）的天然诱导剂）在减少 EBOV 复制方面的显著效果。用hemin处理原代单核细胞衍生巨噬细胞（MDM）、Vero E6细胞、HeLa细胞和人包皮成纤维细胞（HFF1），可使EBOV感染率降低90%以上，而且对感染细胞的毒性极小。抑制HO-1酶的活性和沉默HO-1的表达可阻止hemin介导的EBOV感染抑制，这表明诱导这种细胞内介质在限制EBOV复制方面起着重要作用。hemin诱导的HO-1与EBOV复制之间的反相关性提供了一种潜在的有用治疗模式，这种模式基于刺激细胞对埃博拉病毒感染的先天反应。

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来源期刊

Current Trends in Immunology Medicine-Immunology and Allergy

CiteScore

0.30

自引率

0.00%

发文量

期刊介绍： Computers and Electronics in Agriculture provides international coverage of advances in the development and application of computer hardware, software, electronic instrumentation, and control systems for solving problems in agriculture, including agronomy, horticulture (in both its food and amenity aspects), forestry, aquaculture, and animal/livestock farming. The journal publishes original papers, reviews, and applications notes on topics pertaining to advances in the use of computers or electronics in plant or animal agricultural production, including agricultural soils, water, pests, controlled environments, structures, and wastes, as well as the plants and animals themselves. Post-harvest operations considered part of agriculture (such as drying, storage, logistics, production assessment, trimming and separation of plant and animal material) are also covered. Relevant areas of technology include artificial intelligence, sensors, machine vision, robotics, networking, and simulation modelling.