title: Therapeutic potential of the heme oxygenase-1 inducer hemin against Ebola virus infection.
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.
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hanxia
authors.initials: H
authors.lastname: Huang
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Konduru
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland.
authors.forename: Veronica
authors.initials: V
authors.lastname: Solovena
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhou
authors.affiliation: Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC.
authors.forename: Namita
authors.initials: N
authors.lastname: Kumari
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Center for Sickle Cell Disease, Department of Medicine, Howard University, Washington DC.
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.affiliation: Molecular and Translational Sciences Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland.
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Gerardo G
authors.initials: GG
authors.lastname: Kaplan
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
authors.affiliation: Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Subhash
authors.initials: S
authors.lastname: Dhawan
keywords: Ebola; heme oxygenase-1; hemin; monocytes/macrophages