Evidence map›Paper›PMID 32747502›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2020

Middle East Respiratory Syndrome Coronavirus ORF8b Accessory Protein Suppresses Type I IFN Expression by Impeding HSP70-Dependent Activation of IRF3 Kinase IKKε.

Lok-Yin Roy Wong, Zi-Wei Ye, Pak-Yin Lui, Xuyang Zheng, Shuofeng Yuan, Lin Zhu, Sin-Yee Fung, Kit-San Yuen, Kam-Leung Siu, Man-Lung Yeung and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
0.8field-weighted citation impact, top 15% 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

31 citing papers in PubMed, 44 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

15 authors at 2 institutions in 1 country.

Lok-Yin Roy WongSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0002-0727-8289
Zi-Wei YeState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.ORCID 0000-0002-6446-4299
Pak-Yin LuiSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0003-2879-604X
Xuyang ZhengSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0003-1614-8029
Shuofeng YuanState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.ORCID 0000-0001-7996-1119
Lin ZhuState Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Sin-Yee FungSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0002-5184-6781
Kit-San YuenSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.
Kam-Leung SiuSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong.ORCID 0000-0001-8472-6834
Man-Lung YeungState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
Zongwei CaiState Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Patrick Chiu-Yat WooState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
Kwok-Yung YuenState Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong; and.
Chi-Ping ChanSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong; chancp10@hku.hk dyjin@hku.hk.ORCID 0000-0001-6876-0864
Dong-Yan JinSchool of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong; chancp10@hku.hk dyjin@hku.hk.ORCID 0000-0002-2778-3530
University of Hong Kong · HKHong Kong Baptist University · HK

Funding

TRAINING IN MECHANISMS OF PARASITISMT32AI007511 · NIAID · UNIVERSITY OF IOWA · PI BUTLER, NOAH SULLIVAN, WEBER, MARY · 1996 to 2025
$8.1M
NIAID NIH HHS T32 AI007511
6 · The paper itself

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus causing severe disease and mortality. MERS-CoV infection failed to elicit robust IFN response, suggesting that the virus might have evolved strategies to evade host innate immune surveillance. In this study, we identified and characterized type I IFN antagonism of MERS-CoV open reading frame (ORF) 8b accessory protein. ORF8b was abundantly expressed in MERS-CoV-infected Huh-7 cells. When ectopically expressed, ORF8b inhibited IRF3-mediated IFN-β expression induced by Sendai virus and poly(I:C). ORF8b was found to act at a step upstream of IRF3 to impede the interaction between IRF3 kinase IKKε and chaperone protein HSP70, which is required for the activation of IKKε and IRF3. An infection study using recombinant wild-type and ORF8b-deficient MERS-CoV further confirmed the suppressive role of ORF8b in type I IFN induction and its disruption of the colocalization of HSP70 with IKKε. Ectopic expression of HSP70 relieved suppression of IFN-β expression by ORF8b in an IKKε-dependent manner. Enhancement of IFN-β induction in cells infected with ORF8b-deficient virus was erased when HSP70 was depleted. Taken together, HSP70 chaperone is important for IKKε activation, and MERS-CoV ORF8b suppresses type I IFN expression by competing with IKKε for interaction with HSP70.

Indexed as

BetacoronavirusCell LineCoronavirus InfectionsCOVID-19Enzyme ActivationHSP70 Heat-Shock ProteinsHumansI-kappa B KinaseInterferon Type IMiddle East Respiratory Syndrome CoronavirusPandemicsPneumonia, ViralSARS-CoV-2Viral ProteinsHSP70 Heat-Shock ProteinsI-kappa B KinaseInterferon Type IViral Proteins

Identifiers

PMID32747502
PMCPMC9202338
OpenAlexW3047477951

What OpenQuestion holds

Textmetadata
LicenceTDM
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.