PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
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Zhang Y, Mao D, Roswit WT, Jin X, Patel AC, Patel DA, Agapov E, Wang Z, Tidwell RM, Atkinson JJ, Huang G, McCarthy R, Yu J, Yun NE, Paessler S, Lawson TG, Omattage NS, Brett TJ, Holtzman MJ
PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
Nat Immunol. 2015 Dec;16(12):1215-27. doi: 10.1038/ni.3279. Epub 2015 Oct 19.
- PubMed ID
- 26479788 [ View in PubMed]
- 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.