RESEARCH ARTICLE Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection

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 pro-tect 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 stim-ulated 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 treat-ment. The ISGs induced in wild typemice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression wasmuch higher inWTmice without VLPs than mice treated with VLPs. In EBOV infected Ifnar-/-mice, however, uninhibited viral replica-tion 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 inflam-matory responses. Further analyses showed that VLP protection requires the transcription fac