Evidence map›Paper›PMID 25752576›Full record

ArticleMolecular cell2015

Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production.

Shanping He, Jun Zhao, Shanshan Song, Xiaojing He, Arlet Minassian, Yu Zhou, Junjie Zhang, Kevin Brulois, Yuqi Wang, Jackson Cabo and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 78 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Shanping HeDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Jun ZhaoDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Shanshan SongDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Xiaojing HeDepartment of Pharmacology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75039, USA.
Arlet MinassianDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Yu ZhouDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Junjie ZhangDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Kevin BruloisDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Yuqi WangDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Jackson CaboDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Ebrahim ZandiDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Chengyu LiangDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Jae U JungDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Xuewu ZhangDepartment of Pharmacology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75039, USA.
Pinghui FengDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA. Electronic address: pinghui.feng@usc.edu.
University of Southern California · USSouthwestern Medical Center · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KAPLOWITZ, NEIL · 1995 to 2020
$21.8M
Roles of the K3 and K5 in KSHV Persistence and PathogenesisP01CA180779 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JUNG, JAE U · 2013 to 2017
$7.3M
Role of UVRAG-mediated Autophagy in Tumor SuppressionR01CA140964 · NCI · WISTAR INSTITUTE · PI LIANG, CHENGYU · 2009 to 2025
$5.4M
Proviral Roles of an Innate Immune PathwayR01DE021445 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FENG, PINGHUI · 2011 to 2017
$2.5M
TRIM9-mediated anti-viral immune pathwayR01AI116585 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI OU, J.-H. JAMES · 2015 to 2019
$2.3M
Post-Translational Events Underlying the KSHV vGPCR PathogenesisR01CA134241 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI FENG, PINGHUI · 2009 to 2013
$1.6M
A recombinant virus approach for gamma herpesvirus oncogenesisR21AI105340 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI FENG, PINGHUI · 2014 to 2015
$452k
NCI NIH HHS CA134241NCI NIH HHS P01 CA180779NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089-34NCI NIH HHS R01 CA134241NCI NIH HHS R01 CA140964NIAID NIH HHS R01 AI116585NIAID NIH HHS R21 AI105340NIDCR NIH HHS DE021445NIDCR NIH HHS R01 DE021445NIDDK NIH HHS P30 DK048522
6 · The paper itself

Abstract

RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here, we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologs of phosphoribosylformylglycinamidine synthetase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homolog thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme.

Indexed as

AmidesAnimalsCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell LineCytokinesDEAD Box Protein 58DEAD-box RNA HelicasesEnzyme ActivationFibroblastsGammaherpesvirinaeGene Expression RegulationHEK293 CellsHumansImmune EvasionImmunity, InnateMiceAmidesCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCytokinesDEAD Box Protein 58DEAD-box RNA Helicasesphosphoribosylformylglycinamidine synthetaseReceptors, ImmunologicRIGI protein, humanRNA, Small InterferingRNA, ViralViral Proteins

Identifiers

PMID25752576
PMCPMC4385502
OpenAlexW2078154360

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.