A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-Induced Activation

Publication date: Available online 17 November 2016
Source:Cell Host & Microbe
Author(s): Jun Zhao, Yi Zeng, Simin Xu, Jie Chen, Guobo Shen, Caiqun Yu, David Knipe, Weiming Yuan, Jian Peng, Wenqing Xu, Chao Zhang, Zanxian Xia, Pinghui Feng
RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine production. Protein deamidation is emerging as a post-translational modification that chiefly regulates protein function. We report here that UL37 of herpes simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to block RNA-induced activation. Mass spectrometry analysis identified two asparagine residues in the helicase 2i domain of RIG-I that were deamidated upon UL37 expression or HSV-1 infection. Deamidation rendered RIG-I unable to sense viral dsRNA, thus blocking its ability to trigger antiviral immune responses and restrict viral replication. Purified full-length UL37 and its carboxyl-terminal fragment were sufficient to deamidate RIG-I in vitro. Uncoupling RIG-I deamidation from HSV-1 infection, by engineering deamidation-resistant RIG-I or introducing deamidase-deficient UL37 into the HSV-1 genome, restored RIG-I activation and antiviral immune signaling. Our work identifies a viral deamidase and extends the paradigm of deamidation-mediated suppression of innate immunity by microbial pathogens.

Graphical abstract

Teaser

Herpes simplex virus 1 (HSV-1) blocks innate immune signaling. Here, Zhao et al. report that the HSV-1 UL37 protein deamidates the RNA sensor RIG-I to prevent RNA-induced activation. Uncoupling RIG-I deamidation from its activation restored RIG-I-dependent antiviral immune response and impaired HSV-1 replication.


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