@article{0d5730b9f1c14da484f0233d43b51aa7,
title = "Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases",
abstract = "All viruses with positive-sense RNA genomes replicate on membranous structures in the cytoplasm called replication complexes (RCs). RCs provide an advantageous microenvironment for viral replication, but it is unknown how the host immune system counteracts these structures. Here we show that interferon-gamma (IFNG) disrupts the RC of murine norovirus (MNV) via evolutionarily conserved autophagy proteins and the induction of IFN-inducible GTPases, which are known to destroy the membrane of vacuoles containing bacteria, protists, or fungi. The MNV RC was marked by the microtubule-associated-protein-1-light-chain-3 (LC3) conjugation system of autophagy and then targeted by immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) upon their induction by IFNG. Further, the LC3 conjugation system and the IFN-inducible GTPases were necessary to inhibit MNV replication in mice and human cells. These data suggest that viral RCs can be marked and antagonized by a universal immune defense mechanism targeting diverse pathogens replicating in cytosolic membrane structures.",
keywords = "GBP, GTPase, IRG, LC3, RNA, autophagy, interferon, replication, targeting, virus",
author = "Biering, {Scott B.} and Jayoung Choi and Halstrom, {Rachel A.} and Brown, {Hailey M.} and Beatty, {Wandy L.} and Sanghyun Lee and McCune, {Broc T.} and Erin Dominici and Williams, {Lelia E.} and Orchard, {Robert C.} and Wilen, {Craig B.} and Masahiro Yamamoto and J{\"o}rn Coers and Taylor, {Gregory A.} and Seungmin Hwang",
note = "Funding Information: We thank Drs. Herbert W. Virgin (Washington University School of Medicine in St. Louis), Thirumala-Devi Kanneganti (St. Jude Children's Research Hospital), and Feng Zhang (Broad Institute) for sharing valuable research reagents for this study. This work was supported by startup fund to S.H., and in part by the Brinson Foundation Junior Investigator Grant, Cancer Research Foundation, an Institutional Research Grant (IRG-58-004-53-IRG) from the American Cancer Society, the University of Chicago Digestive Diseases Research Core Center (NIDDK P30DK42086), the University of Chicago Comprehensive Cancer Center Support Grant (P30 CA14599), the Cancer Center Core facilities (DNA sequencing and genotyping, flow cytometry, integrated microscopy, and monoclonal antibody), and the National Center for Advancing Translational Sciences of the NIH (UL1 TR000430). S.B.B. was supported (in part) by NIH T32 GM007183 and H.M.B. was supported (in part) by NIH T32 AI007090. B.T.M. was supported by NCI-NIH award F31CA177194-01. G.A.T. was supported by VA grant I01 BX002369. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = jul,
day = "12",
doi = "10.1016/j.chom.2017.06.005",
language = "English (US)",
volume = "22",
pages = "74--85.e7",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "1",
}