Evidence map›Paper›PMID 37792941›Full record

ArticleScience advances2023

Human cytomegalovirus UL36 inhibits IRF3-dependent immune signaling to counterbalance its immunoenhancement as apoptotic inhibitor.

Yujie Ren, An Wang, Bowen Zhang, Wenting Ji, Xiao-Xu Zhu, Jing Lou, Muhan Huang, Yang Qiu, Xi Zhou

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Yujie RenState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.ORCID 0000-0002-8467-6766
An WangState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
Bowen ZhangState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.ORCID 0009-0009-9079-8645
Wenting JiState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.ORCID 0000-0001-7509-0854
Xiao-Xu ZhuState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
Jing LouState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.ORCID 0000-0002-7337-261X
Muhan HuangState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
Yang QiuState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.ORCID 0000-0001-5152-1242
Xi ZhouState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.ORCID 0000-0002-3846-5079
Chinese Academy of Sciences · CNUniversity of Science and Technology of China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Apoptotic inhibition and immune evasion have particular importance to efficient viral infection, while a dilemma often faced by viruses is that inhibiting apoptosis can up-regulate antiviral immune signaling. Herein, we uncovered that in addition to inhibiting caspase-8/extrinsic apoptosis, human cytomegalovirus (HCMV)-encoded UL36 suppresses interferon regulatory factor 3 (IRF3)-dependent immune signaling by directly targeting IRF3 to abrogate IRF3 interaction with stimulator of interferon genes or TANK-binding kinase 1 and inhibit IRF3 phosphorylation/activation. Although UL36-mediated caspase-8/extrinsic apoptosis inhibition enhances immune signaling, the immunosuppressing activity of UL36 counterbalances this immunoenhancing "side effect" undesirable for virus. Furthermore, we used mutational analyses to show that only the wild-type, but not the UL36 mutant losing either inhibitory activity, is sufficient to support effective HCMV replication in cells, showing the functional importance of the dual inhibition by UL36 for the HCMV life cycle. Together, our findings demonstrate a sophisticated mechanism by which HCMV tightly controls innate immune signaling and extrinsic apoptosis for efficient infection.

Indexed as

CytomegalovirusInterferon Regulatory Factor-3Caspase 8HumansImmune EvasionSignal TransductionCaspase 8Interferon Regulatory Factor-3IRF3 protein, human

Identifiers

PMID37792941
PMCPMC10550242
OpenAlexW4387353091

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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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.