A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases
Authors:Soham Gupta1, Päivi Ylä-Anttila1, Maria G. Masucci1
doi: 10.15698/mic2018.05.633
Volume 5, pp. 259 to 261, published 11/04/2018.
1 Department of Cell and Molecular Biology, Karolinska Institutet, S-17177 Stockholm, Sweden.
Keywords:
Epstein-Barr virus, Herpesvirus, deconjugase, RIG-I signalosome, type I IFN
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflicts of interest.
Please cite this article as:
: Soham Gupta, Päivi Ylä-Anttila, Maria G. Masucci (2018). A novel mechanism for regulation of the type I IFN response by herpesvirus deconjugases. Microbial Cell 5(5): 259-261. doi: 10.15698/mic2018.05.633
© 2018 Gupta et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Upon infection, viral nucleic acids are recognized by germline-encoded pattern-recognition receptors (PRRs), and cytosolic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) that initiate signaling pathways resulting in the production of type I IFN and pro-inflammatory cytokines. Binding of RIG-I to viral nucleic acids triggers the formation of the RIG-I signalosome where RIG-I is ubiquitinated by the TRIM25 ligase and, with the help of 14-3-3 scaffolds, further translocated to mitochondrial anti-viral signalling proteins (MAVS). Subsequent ubiquitination-mediated events trigger transcriptional activation of the effectors of innate immunity. We have found a new mechanism by which herpesviruses interfere with this signalling pathway to favour the establishment of latency and promote virus replication. The cysteine protease encoded in the conserved N-terminal domain of the herpesvirus large tegument protein binds to 14-3-3 proteins and forms a tri-molecular complex with TRIM25, promoting the activation and autoubiquitination of the ligase. RIG-I is recruited to the complex but its ubiquitination is drastically reduced, which effectively inactivates downstream signalling and blocks the type I IFN response.