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

Yong Zhang, Dailing Mao, William T. Roswit, Xiaohua Jin, Anand C. Patel, Dhara A. Patel, Eugene Agapov, Zhepeng Wang, Rose M. Tidwell, Jeffrey J. Atkinson, Guangming Huang, Ronald McCarthy, Jinsheng Yu, Nadezhda E. Yun, Slobodan Paessler, T. Glen Lawson, Natalie S. Omattage, Tom J. Brett, Michael J. Holtzman

Research output: Contribution to journalArticle

50 Scopus citations

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.

Original languageEnglish
Pages (from-to)1215-1227
Number of pages13
JournalNature immunology
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint Dive into the research topics of 'PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection'. Together they form a unique fingerprint.

  • Cite this

    Zhang, Y., Mao, D., Roswit, W. T., Jin, X., Patel, A. C., Patel, D. A., Agapov, E., Wang, Z., Tidwell, R. M., Atkinson, J. J., Huang, G., McCarthy, R., Yu, J., Yun, N. E., Paessler, S., Lawson, T. G., Omattage, N. S., Brett, T. J., & Holtzman, M. J. (2015). PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. Nature immunology, 16(12), 1215-1227. https://doi.org/10.1038/ni.3279