A dRASSF-STRIPAK-Imd-JAK/STAT axis controls antiviral immune response in Drosophila

Rui Shen, Kewei Zheng, Yu Zhou, Xiaofeng Chi, Huimin Pan, Chengfang Wu, Yinan Yang, Yonggang Zheng, Duojia Pan, Bo Liu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Host antiviral immunity suffers strong pressure from rapidly evolving viruses. Identifying host antiviral immune mechanisms has profound implications for developing antiviral strategies. Here, we uncover an essential role for the tumor suppressor Ras-association domain family (RASSF) in Drosophila antiviral response. Loss of dRassf in fat body leads to increased vulnerability to viral infection and impaired Imd pathway activation accompanied by detrimental JAK/STAT signaling overactivation. Mechanistically, dRASSF protects TAK1, a key kinase of Imd pathway, from inhibition by the STRIPAK PP2A phosphatase complex. Activated Imd signaling then employs the effector Relish to interfere with the dimerization of JAK/STAT transmembrane receptor Domeless, therefore preventing excessive JAK/STAT signaling. Moreover, we find that RASSF and STRIPAK PP2A complex are also involved in antiviral response in human cell lines. Our study identifies an important role for RASSF in antiviral immunity and elucidates a dRASSF-STRIPAK-Imd-JAK/STAT signaling axis that ensures proper antiviral responses in Drosophila.

Original languageEnglish (US)
Article number111143
JournalCell Reports
Volume40
Issue number4
DOIs
StatePublished - Jul 26 2022

Keywords

  • antiviral immunity
  • CP: Immunology
  • Drosophila
  • Imd pathway
  • JAK-STAT pathway
  • RASSF
  • STRIPAK PP2A complex

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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