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Abstract

Viral infection activates host defense mechanisms, including the production of type I interferon (IFN) and the apoptosis of infected cells. We investigated whether these two antiviral responses were differentially regulated in infected cells. We showed that the mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK) apoptosis signal–regulating kinase 1 (ASK1) was activated in cells by the synthetic double-stranded RNA analog polycytidylic acid [poly(I:C)] and by RNA viruses, and that ASK1 played an essential role in both the induction of the gene encoding IFN-β (IFNB) and apoptotic cell death. In contrast, we found that the MAPKKK ASK2, a modulator of ASK1 signaling, was essential for ASK1-dependent apoptosis, but not for inducing IFNB expression. Furthermore, genetic deletion of either ASK1 or ASK2 in mice promoted the replication of influenza A virus in the lung. These results indicated that ASK1 and ASK2 are components of the antiviral defense mechanism and suggested that ASK2 acts as a key modulator that promotes apoptosis rather than the type I IFN response. Because ASK2 is selectively present in epithelium-rich tissues, such as the lung, ASK2-dependent apoptosis may contribute to an antiviral defense in tissues with a rapid repair rate in which cells could be readily replaced.UTokyo Research掲載「生きるべきか死ぬべきか」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/to-be-or-not-to-be-that-is-the-question.html

UTokyo Research "To be, or not to be: That is the question" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/to-be-or-not-to-be-that-is-the-question.html

Journal

  • Science signaling

    Science signaling 8(388), ra78, 2015-08-04

    American Association for the Advancement of Science

Codes

  • NII Article ID (NAID)
    120006348502
  • NII NACSIS-CAT ID (NCID)
    AA12315525
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1945-0877
  • Data Source
    IR 
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