Ebola virus does not block apoptotic signaling pathways

Judith Olejnik, Kristina M. Schmidt, Elke Mühlberger, Jesus Alonso, Jean L. Patterson, Zhen Yan, Wei Wang, Andrea Marzi, Hideki Ebihara, Jinghua Yang, Elena Ryabchikova

    Research output: Contribution to journalArticle

    18 Scopus citations

    Abstract

    Since viruses rely on functional cellular machinery for efficient propagation, apoptosis is an important mechanism to fight viral infections. In this study, we sought to determine the mechanism of cell death caused by Ebola virus (EBOV) infection by assaying formultiple stages of apoptosis and hallmarks of necrosis. Our data indicate that EBOV does not induce apoptosis in infected cells but rather leads to a nonapoptotic form of cell death. Ultrastructural analysis confirmed necrotic cell death of EBOV-infected cells. To investigate if EBOV blocks the induction of apoptosis, infected cells were treated with different apoptosis-inducing agents. Surprisingly, EBOV-infected cells remained sensitive toapoptosis induced by external stimuli. Neither receptor- nor mitochondrion-mediated apoptosis signaling was inhibited in EBOV infection. Although double-stranded RNA (dsRNA)-induced activation of protein kinase R (PKR) was blocked in EBOV-infected cells, induction ofapoptosis mediated by dsRNA was not suppressed. When EBOV-infected cells were treated with dsRNA-dependent caspase recruiter (dsCARE), an antiviral protein that selectively induces apoptosis in cells containing dsRNA, virus titers were strongly reduced. These data show that the inability of EBOV to block apoptotic pathways may open up new strategies toward the development of antiviral therapeutics.

    Original languageEnglish (US)
    Pages (from-to)5384-5396
    Number of pages13
    JournalJournal of Virology
    Volume87
    Issue number10
    DOIs
    Publication statusPublished - May 1 2013

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    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

    Cite this

    Olejnik, J., Schmidt, K. M., Mühlberger, E., Alonso, J., Patterson, J. L., Yan, Z., ... Ryabchikova, E. (2013). Ebola virus does not block apoptotic signaling pathways. Journal of Virology, 87(10), 5384-5396. https://doi.org/10.1128/JVI.01461-12