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Cell Host Microbe. 2016 Dec 14;20(6):770-784. doi: 10.1016/j.chom.2016.10.011. Epub 2016 Nov 17.

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

Author information

1
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Street, Los Angeles, CA 90033, USA.
2
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Street, Los Angeles, CA 90033, USA; Division of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
3
Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA.
4
Department of Chemistry, Dornsife College of Arts, Letters, and Sciences, University of Southern California, LJS 369, 840 Downey Way, Los Angeles, CA 90089, USA.
5
Department of Microbiology and Molecular Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
6
Division of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
7
State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan 410008, China.
8
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Street, Los Angeles, CA 90033, USA. Electronic address: pinghui.feng@usc.edu.

Abstract

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.

KEYWORDS:

ATPase/helicase; RIG-I; RNA-sensing; UL37; deamidation; herpesvirus; immune evasion

PMID:
27866900
PMCID:
PMC5159239
DOI:
10.1016/j.chom.2016.10.011
[Indexed for MEDLINE]
Free PMC Article

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