Epizootic hemorrhagic disease virus induces and benefits from cell stress, autophagy, and apoptosis

Ben Shai, Eran Schmukler, Roy Yaniv, Naomi Ziv, Galit Horn, Velizar Bumbarov, Hagai Yadin, Nechama I. Smorodinsky, Eran Bacharach, Ronit Pinkas-Kramarski, Marcelo Ehrlich

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים


The mode and timing of virally induced cell death hold the potential of regulating viral yield, viral transmission, and the severity of virally induced disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the signal transduction pathways involved in this process, and the consequence of their inhibition have yet to be characterized. Here, we report that the Ibaraki strain of EHDV2 (EHDV2-IBA) induces apoptosis, autophagy, a decrease in cellular protein synthesis, the activation of c-Jun N-terminal kinase (JNK), and the phosphorylation of the JNK substrate c-Jun. The production of infectious virions decreased upon inhibition of apoptosis with the pan-caspase inhibitor Q-VD-OPH (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone), upon inhibition of autophagy with 3-methyladenine or via the knockout of the autophagy regulator Atg5, or upon treatment of infected cells with the JNK inhibitor SP600125 or the cyclin-dependent kinase (CDK) inhibitor roscovitine, which also inhibited c-Jun phosphorylation. Moreover, Q-VD-OPH, SP600125, and roscovitine partially reduced EHDV2-IBA-induced cell death, and roscovitine diminished the induction of autophagy by EHDV2-IBA. Taken together, our results imply that EHDV induces and benefits from the activation of signaling pathways involved in cell stress and death.

שפה מקוריתאנגלית
עמודים (מ-עד)13397-13408
מספר עמודים12
כתב עתJournal of Virology
מספר גיליון24
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - דצמ׳ 2013

ASJC Scopus subject areas

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  • ???subjectarea.asjc.2400.2403???
  • ???subjectarea.asjc.1100.1109???
  • ???subjectarea.asjc.2400.2406???

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