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PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection

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...

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Autores principales: Zhang, Yong, Mao, Dailing, Roswit, William T, Jin, Xiaohua, Patel, Anand C, Patel, Dhara A, Agapov, Eugene, Wang, Zhepeng, Tidwell, Rose M, Atkinson, Jeffrey J, Huang, Guangming, McCarthy, Ronald, Yu, Jinsheng, Yun, Nadezhda E, Paessler, Slobodan, Lawson, T Glen, Omattage, Natalie S, Brett, Tom J, Holtzman, Michael J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653074/
https://www.ncbi.nlm.nih.gov/pubmed/26479788
http://dx.doi.org/10.1038/ni.3279
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author Zhang, Yong
Mao, Dailing
Roswit, William T
Jin, Xiaohua
Patel, Anand C
Patel, Dhara A
Agapov, Eugene
Wang, Zhepeng
Tidwell, Rose M
Atkinson, Jeffrey J
Huang, Guangming
McCarthy, Ronald
Yu, Jinsheng
Yun, Nadezhda E
Paessler, Slobodan
Lawson, T Glen
Omattage, Natalie S
Brett, Tom J
Holtzman, Michael J
author_facet Zhang, Yong
Mao, Dailing
Roswit, William T
Jin, Xiaohua
Patel, Anand C
Patel, Dhara A
Agapov, Eugene
Wang, Zhepeng
Tidwell, Rose M
Atkinson, Jeffrey J
Huang, Guangming
McCarthy, Ronald
Yu, Jinsheng
Yun, Nadezhda E
Paessler, Slobodan
Lawson, T Glen
Omattage, Natalie S
Brett, Tom J
Holtzman, Michael J
author_sort Zhang, Yong
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ni.3279) contains supplementary material, which is available to authorized users.
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spelling pubmed-46530742016-05-18 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection Zhang, Yong Mao, Dailing Roswit, William T Jin, Xiaohua Patel, Anand C Patel, Dhara A Agapov, Eugene Wang, Zhepeng Tidwell, Rose M Atkinson, Jeffrey J Huang, Guangming McCarthy, Ronald Yu, Jinsheng Yun, Nadezhda E Paessler, Slobodan Lawson, T Glen Omattage, Natalie S Brett, Tom J Holtzman, Michael J Nat Immunol Article 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. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ni.3279) contains supplementary material, which is available to authorized users. Nature Publishing Group UK 2015-12-01 2015 /pmc/articles/PMC4653074/ /pubmed/26479788 http://dx.doi.org/10.1038/ni.3279 Text en © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Zhang, Yong
Mao, Dailing
Roswit, William T
Jin, Xiaohua
Patel, Anand C
Patel, Dhara A
Agapov, Eugene
Wang, Zhepeng
Tidwell, Rose M
Atkinson, Jeffrey J
Huang, Guangming
McCarthy, Ronald
Yu, Jinsheng
Yun, Nadezhda E
Paessler, Slobodan
Lawson, T Glen
Omattage, Natalie S
Brett, Tom J
Holtzman, Michael J
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
title PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
title_full PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
title_fullStr PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
title_full_unstemmed PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
title_short PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection
title_sort parp9-dtx3l ubiquitin ligase targets host histone h2bj and viral 3c protease to enhance interferon signaling and control viral infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653074/
https://www.ncbi.nlm.nih.gov/pubmed/26479788
http://dx.doi.org/10.1038/ni.3279
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