Tula hantavirus triggers pro-apoptotic signals of ER stress in Vero E6 cells

Xiao-Dong Li, Hilkka Lankinen, Niina Putkuri, Olli Vapalahti, Antti Vaheri

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    "Tula virus is a member of the Hantavirus genus of the family Bunyaviridae. Viruses of this family have an unusual pattern of intracellular maturation at the ER-Golgi compartment. We recently found that Tula virus, similar to several other hantaviruses, is able to induce apoptosis in cultured cells [Li, X.D., Kukkonen, S., Vapalahti, O., Plyusnin, A., Lankinen, H., Vaheri, A., 2004. Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. J. Gen. Virol. 85, 3261-3268.1. However, the cellular mechanisms remain to be clarified. In this study, we demonstrate that the progressive replication of Tula virus in Vero E6 cells initiates several death programs that are intimately associated with ER stress: (1) early activation of ER-resident caspase-12; (2) phosphorylation of Jun NH2-terminal kinase (JNK) and its downstream target transcriptional factor, c-jun; (3) induction of the pro-apoptotic transcriptional factor, growth arrest- and DNA damage-inducible gene 153, or C/EBP homologous protein (Gadd153/chop); and (4) changes in the ER-membrane protein BAP31 implying cross-talk with the mitochondrial apoptosis pathway. Furthermore, we confirmed that a sustained ER stress was induced marked by an increased expression of an ER chaperone Grp78/BiP. Taken together, we have identified involvement of ER stress-mediated death program in Tula virus-infected Vero E6 cells which provides a new approach to understand the mechanisms in hantavirus-induced apoptosis. (C) 2005 Elsevier Inc. All rights reserved."
    Original languageEnglish
    JournalVirology
    Volume333
    Issue number1
    Pages (from-to)180-189
    Number of pages10
    ISSN0042-6822
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 413 Veterinary science
    • virustaudit
    • stressi
    • solut

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