Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against Ebola virus infection

Natarajan Ayithan; Steven B Bradfute; Scott M Anthony; Kelly S Stuthman; Sina Bavari; Mike Bray; Keiko Ozato

doi:10.1371/journal.pone.0118345

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Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against Ebola virus infection

Journal article

Open access

Peer reviewed

Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against Ebola virus infection

Natarajan Ayithan, Steven B Bradfute, Scott M Anthony, Kelly S Stuthman, Sina Bavari, Mike Bray and Keiko Ozato

PloS one, Vol.10(2), pp.e0118345-e0118345

2015

DOI: 10.1371/journal.pone.0118345

PMCID: PMC4342244

PMID: 25719445

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Abstract

Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar-/- mice. Accordingly, EBOV infected Ifnar-/- mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar-/- mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host.

Animals

Dendritic Cells - immunology

Hemorrhagic Fever, Ebola - immunology

Hemorrhagic Fever, Ebola - prevention & control

Interferon Regulatory Factors - genetics

Interferon Regulatory Factors - metabolism

Interferon Type I - genetics

Interferon Type I - metabolism

Macrophages - immunology

Mice

Mice, Inbred BALB C

Mice, Inbred C57BL

Post-Exposure Prophylaxis

Receptor, Interferon alpha-beta - genetics

Receptor, Interferon alpha-beta - metabolism

Signal Transduction

Vaccines, Virus-Like Particle - immunology

Vaccines, Virus-Like Particle - therapeutic use

Details

Title: Subtitle: Virus-like particles activate type I interferon pathways to facilitate post-exposure protection against Ebola virus infection
Creators: Natarajan Ayithan - National Institutes of Health
Steven B Bradfute - United States Department of the Army
Scott M Anthony - United States Department of the Army
Kelly S Stuthman - United States Department of the Army
Sina Bavari - United States Department of the Army
Mike Bray - National Institutes of Health
Keiko Ozato - National Institutes of Health
Resource Type: Journal article
Publication Details: PloS one, Vol.10(2), pp.e0118345-e0118345
DOI: 10.1371/journal.pone.0118345
PMID: 25719445
PMCID: PMC4342244
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: Intramural NIH HHS
Language: English
Date published: 2015
Academic Unit: Pathology
Record Identifier: 9984183986002771

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