Journal article
Interferon-γ Inhibits Ebola Virus Infection
PLoS pathogens, Vol.11(11), pp.e1005263-e1005263
2015
DOI: 10.1371/journal.ppat.1005263
PMCID: PMC4643030
PMID: 26562011
Abstract
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. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.
Details
- Title: Subtitle
- Interferon-γ Inhibits Ebola Virus Infection
- Creators
- Bethany A Rhein - Department of Microbiology, The University of Iowa, Iowa City, Iowa, United States of AmericaLinda S Powers - University of Iowa, Internal MedicineKai Rogers - University of Iowa Hospitals and ClinicsManu Anantpadma - Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas, United States of AmericaBrajesh K Singh - University of Iowa, Stead Family Department of PediatricsYasuteru Sakurai - Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas, United States of AmericaThomas Bair - Iowa Institute for Human Genetics, The University of Iowa, Iowa City, Iowa, United States of AmericaCatherine Miller-Hunt - Department of Microbiology, The University of Iowa, Iowa City, Iowa, United States of AmericaPatrick Sinn - University of Iowa, Pulmonary MedicineRobert A Davey - Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, Texas, United States of AmericaMartha M Monick - University of Iowa, Internal MedicineWendy Maury - University of Iowa, Microbiology and Immunology
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.11(11), pp.e1005263-e1005263
- DOI
- 10.1371/journal.ppat.1005263
- PMID
- 26562011
- PMCID
- PMC4643030
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Grant note
- P30 ES005605 / NIEHS NIH HHS R21 HL109589 / NHLBI NIH HHS R21HL109589 / NHLBI NIH HHS T32 GM007337 / NIGMS NIH HHS T32AU996343 / PHS HHS R01 AI077519 / NIAID NIH HHS R01 HL096625 / NHLBI NIH HHS P30ES005605 / NIEHS NIH HHS P30 DK054759 / NIDDK NIH HHS R01AI077519 / NIAID NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984206855202771
Metrics
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