Ebola Virus Does Not Induce Stress Granule Formation during Infection and Sequesters Stress Granule Proteins within Viral Inclusions

Emily V. Nelson, Kristina M. Schmidt, Laure R. Deflubé, Sultan Doĝanay, Logan Banadyga, Judith Olejnik, Adam J. Hume, Elena Ryabchikova, Hideki Ebihara, Nancy Kedersha, Taekjip Ha, Elke Muhlberger

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

A hallmark of Ebola virus (EBOV) infection is the formation of viral inclusions in the cytoplasm of infected cells. These viral inclusions contain the EBOV nucleocapsids and are sites of viral replication and nucleocapsid maturation. Although there is growing evidence that viral inclusions create a protected environment that fosters EBOV replication, little is known about their role in the host response to infection. The cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation and translational arrest mediated by the phosphorylation of a translation initiation factor, the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we show that selected SG proteins are sequestered within EBOV inclusions, where they form distinct granules that colocalize with viral RNA. These inclusion-bound (IB) granules are functionally and structurally different from canonical SGs. Formation of IB granules does not indicate translational arrest in the infected cells. We further show that EBOV does not induce formation of canonical SGs or eIF2α phosphorylation at any time postinfection but is unable to fully inhibit SG formation induced by different exogenous stressors, including sodium arsenite, heat, and hippuristanol. Despite the sequestration of SG marker proteins into IB granules, canonical SGs are unable to form within inclusions, which we propose might be mediated by a novel function of VP35, which disrupts SG formation. This function is independent of VP35's RNA binding activity. Further studies aim to reveal the mechanism for SG protein sequestration and precise function within inclusions.

Original languageEnglish (US)
Pages (from-to)7268-7284
Number of pages17
JournalJournal of Virology
Volume90
Issue number16
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Nelson, E. V., Schmidt, K. M., Deflubé, L. R., Doĝanay, S., Banadyga, L., Olejnik, J., Hume, A. J., Ryabchikova, E., Ebihara, H., Kedersha, N., Ha, T., & Muhlberger, E. (2016). Ebola Virus Does Not Induce Stress Granule Formation during Infection and Sequesters Stress Granule Proteins within Viral Inclusions. Journal of Virology, 90(16), 7268-7284. https://doi.org/10.1128/JVI.00459-16