Dataset Information


Interferon-γ inhibition of Ebola virus infection [Monocyte-derived macrophage]

ABSTRACT: Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals. Overall design: Total RNA was isolated from monocyte-derived macrophages (MDMs) from healthy individuals differentiated in the presence of 50 ng/mL of M-CSF for 6 days and then treated with or without 20 ng/mL of IFNg for 24 hours.

INSTRUMENT(S): [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]

SUBMITTER: Thomas B Bair  

PROVIDER: GSE64996 | GEO | 2015-10-20



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Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furt  ...[more]

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