@article{dd01f5143bdb4762b2bb9f9931e58221,
title = "HOIL1 is essential for the induction of type I and III interferons by MDA5 and regulates persistent murine norovirus infection",
abstract = "The linear ubiquitin chain assembly complex (LUBAC), composed of heme-oxidized IRP2 ubiquitin ligase 1 (HOIL1), HOIL1-interacting protein (HOIP), and SHANK-associated RH domain-interacting protein (SHARPIN), is a crucial regulator of multiple immune signaling pathways. In humans, HOIL1 or HOIP deficiency is associated with an immune disorder involving autoinflammation, immunodeficiency, and inflammatory bowel disease (IBD)-like symptoms. During viral infection, LUBAC is reported to inhibit the induction of interferon (IFN) by the cytosolic RNA sensor retinoic acid-inducible gene I (RIG-I). Surprisingly, we found that HOIL1 is essential for the induction of both type I and type III IFNs, as well as the phosphorylation of IFN regulatory factor 3 (IRF3), during murine norovirus (MNoV) infection in cultured dendritic cells. The RIG-I-like receptor, melanoma differentiation-associated protein 5 (MDA5), is also required for IFN induction and IRF3 phosphorylation during MNoV infection. Furthermore, HOIL1 and MDA5 were required for IFN induction after Theiler's murine encephalomyelitis virus infection and poly(I·C) transfection, but not Sendai virus or vesicular stomatitis virus infection, indicating that HOIL1 and LUBAC are required selectively for MDA5 signaling. Moreover, Hoil1/ mice exhibited defective control of acute and persistent murine norovirus infection and defective regulation of MNoV persistence by the microbiome as also observed previously for mice deficient in interferon lambda (IFN-) receptor, signal transducer and activator of transcription factor 1 (STAT1), and IRF3. These data indicate that LUBAC plays a critical role in IFN induction to control RNA viruses sensed by MDA5.",
keywords = "HOIL1, Interferons, LUBAC, MDA5, Norovirus, Ubiquitination",
author = "MacDuff, {Donna A.} and Baldridge, {Megan T.} and Qaqish, {Arwa M.} and Nice, {Timothy J.} and Darbandi, {Azad D.} and Hartley, {Victoria L.} and Peterson, {Stefan T.} and Miner, {Jonathan J.} and Kazuhiro Iwai and Skip Virgin",
note = "Funding Information: We thank D. Kreamalmeyer for animal care and breeding, M. Wood and members of the Virgin laboratory for manuscript reviews and discussions, C. S. Hsieh (Washington University) for providing the Cas9 knock-in mice crossed with Deleter-cre mice, M. P. Kamps (University of California, San Diego [UCSD)] for providing the HoxB8 expression system, R. Orchard for the Cd300lf/ ER-HoxB8 cells, H. Lipton for TMEV strain GDVII, S. Whelan and N. Sarute for VSV-GFP, and S. Garrett for initiating the SeV study. H.W.V. was supported by National Institutes of Health (NIH) grant R01 U19AI109725, Crohn's and Colitis Foundation Genetics Initiative grant 326556. M.T.B. was supported by NIH training grant 5T32CA009547 and NIH K22AI127846. T.J.N. was supported by NIH training grant 5T32A100716334 and postdoctoral fellowships from the American Cancer Society. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Funding Information: H.W.V. was supported by National Institutes of Health (NIH) grant R01 U19AI109725, Crohn{\textquoteright}s and Colitis Foundation Genetics Initiative grant 326556. M.T.B. was supported by NIH training grant 5T32CA009547 and NIH K22AI127846. T.J.N. was supported by NIH training grant 5T32A100716334 and postdoctoral fellowships from the American Cancer Society. Publisher Copyright: Copyright {\textcopyright} 2018 American Society for Microbiology. All Rights Reserved.",
year = "2018",
doi = "10.1128/JVI.01368-18",
language = "English",
volume = "92",
journal = "Journal of Virology",
issn = "0022-538X",
number = "23",
}