title: Ebola virus does not block apoptotic signaling pathways.
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 for multiple 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 to apoptosis 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 of apoptosis 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.
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Olejnik
authors.forename: Jesus
authors.initials: J
authors.lastname: Alonso
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Schmidt
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.forename: Jean L
authors.initials: JL
authors.lastname: Patterson
authors.forename: Elena
authors.initials: E
authors.lastname: Ryabchikova
authors.forename: Elke
authors.initials: E
authors.lastname: Mühlberger
mesh_terms: D000818:Animals; D016923:Cell Death; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000276:immunology* / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D015398:Signal Transduction; D014709:Vero Cells