@article{4d0e5f336a52498b9b8acb62729b5e04,
title = "STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection",
abstract = "Cohesin is a multi-subunit nuclear protein complex that coordinates sister chromatid separation during cell division. Highly frequent somatic mutations in genes encoding core cohesin subunits have been reported in multiple cancer types. Here, using a genome-wide CRISPR-Cas9 screening approach to identify host dependency factors and novel innate immune regulators of rotavirus (RV) infection, we demonstrate that the loss of STAG2, an important component of the cohesin complex, confers resistance to RV replication in cell culture and human intestinal enteroids. Mechanistically, STAG2 deficiency results in spontaneous genomic DNA damage and robust interferon (IFN) expression via the cGAS-STING cytosolic DNA-sensing pathway. The resultant activation of JAK-STAT signaling and IFN-stimulated gene (ISG) expression broadly protects against virus infections, including RVs. Our work highlights a previously undocumented role of the cohesin complex in regulating IFN homeostasis and identifies new therapeutic avenues for manipulating the innate immunity.",
author = "Siyuan Ding and Jonathan Diep and Ningguo Feng and Lili Ren and Bin Li and Ooi, {Yaw Shin} and Xin Wang and Brulois, {Kevin F.} and Yasukawa, {Linda L.} and Xingnan Li and Kuo, {Calvin J.} and Solomon, {David A.} and Carette, {Jan E.} and Greenberg, {Harry B.}",
note = "Funding Information: We would like to thank all members in the Greenberg lab for their support and discussion of the project. We thank Dr. Mrinmoy Sanyal for help in cell sorting to generate CRISPR knockout cells. We are grateful to Dr. John T. Patton (University of Maryland) and Dr. Terence S. Dermody (University of Pittsburgh) for discussion of the project. This work is supported by NIH grants R01 AI021362 and R56 AI021362 and by VA Merit review grant GRH0022 awarded to H.B.G. S.D. is supported by a Walter V. and Idun Berry Postdoctoral Fellowship, a Stanford Institute for Immunity, Transplantation and Infection (ITI) Young Investigator Award, and the Early Career Award from the Thrasher Research Fund. H.B.G., X.L., and C.J.K. are supported by NIH U19 AI116484. D.A.S. is supported by NIH DP5 OD021403. J.E.C. is supported by NIH DP2 AI104557. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-03782-z",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
number = "1",
}