Evidence map›Paper›PMID 26468527›Full record

ArticleJournal of virology2016

Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses.

Guanghui Yi, Yahong Wen, Chang Shu, Qingxia Han, Kouacou V Konan, Pingwei Li, C Cheng Kao

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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, 1 synthesis or guideline pooled it.

  1. Pooled it
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  17. Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Guanghui YiDepartment of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA gyi@indiana.edu.
Yahong WenDepartment of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA.
Chang ShuDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
Qingxia HanCenter for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Kouacou V KonanCenter for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Pingwei LiDepartment of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
C Cheng KaoDepartment of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA.

Funding

RNA-dependent RNA Synthesis by the Hepatitis C VirusR01AI073335 · NIAID · TRUSTEES OF INDIANA UNIVERSITY · PI KAO, CHENG C · 2008 to 2012
$1.5M
Nonstructural 4B Protein and Hepatitus C Virus ProductionR21AI097858 · NIAID · ALBANY MEDICAL COLLEGE · PI KONAN, KOUACOU V. · 2012 to 2013
$423k
NIAID NIH HHS 1R01AI073335NIAID NIH HHS R01 AI073335NIAID NIH HHS R21 AI097858
6 · The paper itself

Abstract

unlabelledThe cyclic dinucleotide 2',3'-cGAMP can bind the adaptor protein STING (stimulator of interferon [IFN] genes) to activate the production of type I IFNs and proinflammatory cytokines. We found that cGAMP added to the culture medium could suppress the replication of the hepatitis C virus (HCV) genotype 1b strain Con1 subgenomic replicon in human hepatoma cells. Knockdown of STING expression diminished the inhibitory effect on replicon replication, while overexpression of STING enhanced the inhibitory effects of cGAMP. The addition of cGAMP into 1b/Con1 replicon cells significantly increased the expression of type I IFNs and antiviral interferon-stimulated genes. Unexpectedly, replication of the genotype 2a JFH1 replicon and infectious JFH1 virus was less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon. Using chimeric replicons, 2a NS4B was identified to confer resistance to cGAMP. Transient expression of 2a NS4B resulted in a pronounced inhibitory effect on STING-mediated beta IFN (IFN-β) reporter activation compared to that of 1b NS4B. 2a NS4B was found to suppress STING accumulation in a dose-dependent manner. The predicted transmembrane domain of 2a NS4B was required to inhibit STING accumulation. These results demonstrate a novel genotype-specific inhibition of the STING-mediated host antiviral immune response. IMPORTANCE: The cyclic dinucleotide cGAMP was found to potently inhibit the replication of HCV genotype 1b Con1 replicon but was less effective for the 2a/JFH1 replicon and infectious JFH1 virus. The predicted transmembrane domain in 2a NS4B was shown to be responsible for the decreased sensitivity to cGAMP. The N terminus of NS4B has been reported to suppress STING-mediated signaling by disrupting the interaction of STING and TBK1 and/or MAVS. We show that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation.

Indexed as

Host-Pathogen InteractionsImmune EvasionImmunity, InnateCell Line, TumorGenotypeHepacivirusHepatocytesHumansMembrane ProteinsSTING ProteinViral Nonstructural ProteinsMembrane ProteinsNS4B protein, flavivirusSTING1 protein, humanSTING ProteinViral Nonstructural Proteins

Identifiers

PMID26468527
PMCPMC4702547

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.