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

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.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Zhao J,Zeng Y,Xu S,Chen J,Shen G,Yu C,Knipe D,Yuan W,Peng J,Xu W,Zhang C,Xia Z,Feng P

doi

10.1016/j.chom.2016.10.011

subject

Has Abstract

pub_date

2016-12-14 00:00:00

pages

770-784

issue

6

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(16)30437-1

journal_volume

20

pub_type

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