@article{bd6eadcde4d64eb5aa2c1bba8713b999,
title = "PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection",
abstract = "Enhancing the response to interferon could offer an immunological advantage to the host. In support of this concept, we used a modified form of the transcription factor STAT1 to achieve hyper-responsiveness to interferon without toxicity and markedly improve antiviral function in transgenic mice and transduced human cells. We found that the improvement depended on expression of a PARP9-DTX3L complex with distinct domains for interaction with STAT1 and for activity as an E3 ubiquitin ligase that acted on host histone H2BJ to promote interferon-stimulated gene expression and on viral 3C proteases to degrade these proteases via the immunoproteasome. Thus, PARP9-DTX3L acted on host and pathogen to achieve a double layer of immunity within a safe reserve in the interferon signaling pathway.",
author = "Yong Zhang and Dailing Mao and Roswit, {William T.} and Xiaohua Jin and Patel, {Anand C.} and Patel, {Dhara A.} and Eugene Agapov and Zhepeng Wang and Tidwell, {Rose M.} and Atkinson, {Jeffrey J.} and Guangming Huang and Ronald McCarthy and Jinsheng Yu and Yun, {Nadezhda E.} and Slobodan Paessler and Lawson, {T. Glen} and Omattage, {Natalie S.} and Brett, {Tom J.} and Holtzman, {Michael J.}",
note = "Funding Information: We thank A.C. Palmenberg (University of Wisconsin) for mouse monoclonal antibody to EMCV 3D; G. Stark (Cleveland Clinic) for the U3A cell line; A. Winoto (University of California, Berkeley) for plasmid pCI-His-Ub; E. Yeh (University of Texas, Houston) for plasmid pHA-Ubiquitin; J. Gern (University of Wisconsin) for HRV A16; and G. Amarasinghe (Washington University) for respiratory syncytial virus NS1. Supported by the US National Institutes of Health (National Institute of Allergy and Infectious Diseases Asthma and Allergic Diseases Cooperative Research Center U19-AI070489 to M.J.H.; U54-AI05160 to M.J.H.; RO1-AI111605 to M.J.H.; and R15-AI099134 to T.G.L.) and the Martin Schaeffer Fund (M.J.H.). Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",
year = "2015",
month = dec,
day = "1",
doi = "10.1038/ni.3279",
language = "English",
volume = "16",
pages = "1215--1227",
journal = "Nature Immunology",
issn = "1529-2908",
number = "12",
}