@article{88404fe9b07549aa8df4260f8adff0be,
title = "A dRASSF-STRIPAK-Imd-JAK/STAT axis controls antiviral immune response in Drosophila",
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.",
keywords = "CP: Immunology, Drosophila, Imd pathway, JAK-STAT pathway, RASSF, STRIPAK PP2A complex, antiviral immunity",
author = "Rui Shen and Kewei Zheng and Yu Zhou and Xiaofeng Chi and Huimin Pan and Chengfang Wu and Yinan Yang and Yonggang Zheng and Duojia Pan and Bo Liu",
note = "Funding Information: We would like to thank Dr. Nic Tapon (The Francis Crick Institute) for dRASSF antibody, Dr. Xuelian Luo (UT Southwestern Medical Center) for wild-type and SLMAP KO 293FT cells, Dr. Bruce Edgar (University of Utah) for NP1-Gal4 fly, Dr. Erika Bach (New York University) for UAS-Upd1 and UAS-Hop Tum−1 flies, Dr. Neal Silverman (University of Massachusetts Medical School) for Ecc15, Dr. Lei Pan (Institut Pasteur of Shanghai) for VSV and DCV, and Drs. Paul Friesen and Paul Ahlquist (University of Wisconsin-Madison) for FHV. We thank Bloomington Drosophila Stock Center (BDSC), Vienna Drosophila Resource Center (VDRC), Drosophila Genomics Resource Center (DGRC), and Developmental Studies Hybridoma Bank (DSHB) for fly strains and reagents. This study was supported in part by grants from National Natural Science Foundation of China ( 31970891 and 32170873 to B.L.), the National Key Research and Development Program of China ( 2019YFA0802002 ), and the NIH ( EY015708 to D.P.). D.P. is an investigator of the Howard Hughes Medical Institute. Funding Information: We would like to thank Dr. Nic Tapon (The Francis Crick Institute) for dRASSF antibody, Dr. Xuelian Luo (UT Southwestern Medical Center) for wild-type and SLMAP KO 293FT cells, Dr. Bruce Edgar (University of Utah) for NP1-Gal4 fly, Dr. Erika Bach (New York University) for UAS-Upd1 and UAS-HopTum−1 flies, Dr. Neal Silverman (University of Massachusetts Medical School) for Ecc15, Dr. Lei Pan (Institut Pasteur of Shanghai) for VSV and DCV, and Drs. Paul Friesen and Paul Ahlquist (University of Wisconsin-Madison) for FHV. We thank Bloomington Drosophila Stock Center (BDSC), Vienna Drosophila Resource Center (VDRC), Drosophila Genomics Resource Center (DGRC), and Developmental Studies Hybridoma Bank (DSHB) for fly strains and reagents. This study was supported in part by grants from National Natural Science Foundation of China (31970891 and 32170873 to B.L.), the National Key Research and Development Program of China (2019YFA0802002), and the NIH (EY015708 to D.P.). D.P. is an investigator of the Howard Hughes Medical Institute. B.L. conceived the project. R.S. K.Z. Y.-G.Z. D.P. and B.L. designed experiments and analyzed data. R.S. K.Z. Y.Z. X.C. H.P. C.W. Y.Y. Y.-G.Z. and B.L. performed the experiments. D.P. and B.L. supervised the study. Y.-G.Z. and B.L. wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = jul,
day = "26",
doi = "10.1016/j.celrep.2022.111143",
language = "English (US)",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}