Evidence map›Paper›PMID 41253770›Full record

ArticleNature communications2025

UHRF1 restricts HCoV-229E infection through epigenetic silencing of the viral receptor APN.

Pengcheng Wang, Ziqiao Wang, Fei Feng, Lisha Yin, Yuyuan Zhang, Zhichao Gao, Jiannan Chen, Ping Zhang, Shuiqiao Yuan, Qiang Ding and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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.

Pengcheng Wang *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-0918-0082
Ziqiao Wang *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Fei Feng *Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Lisha Yin *Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yuyuan ZhangKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Zhichao GaoKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Jiannan ChenKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Ping ZhangDepartment of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.ORCID http://orcid.org/0000-0002-5400-8767
Shuiqiao YuanInstitute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.ORCID http://orcid.org/0000-0003-1460-7682
Qiang DingCenter for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0002-6226-869X
Yue HongSchool of Life and Health Sciences, Hainan Province Key Laboratory of One Health, Collaborative Innovation Center of Life and Health, Hainan University, Haikou, China.
Yuanlin SongDepartment of Pulmonary Medicine, Zhongshan Hospital, Shanghai Key Laboratory of Lung inflammation and injury, Fudan University, Shanghai, China.
Chun LiDepartment of Pulmonary Medicine, Zhongshan Hospital, Shanghai Key Laboratory of Lung inflammation and injury, Fudan University, Shanghai, China. li.chun@zs-hospital.sh.cn.
Jincun ZhaoState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangzhou, China. zhaojincun@gird.cn.ORCID http://orcid.org/0000-0003-2515-5589
Rong ZhangKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. rong_zhang@fudan.edu.cn.ORCID http://orcid.org/0000-0003-2941-4808

Funding

China Postdoctoral Science Foundation 2023M740658National Natural Science Foundation of China (National Science Foundation of China) 32041005National Natural Science Foundation of China (National Science Foundation of China) 82341084
6 · The paper itself

Abstract

The emergence of SARS-CoV-2 has posed significant threats to global health, particularly for the older population. Similarly, common human coronaviruses, such as HCoV-229E, which typically cause mild cold-like symptoms, can lead to severe diseases, underscoring the need to understand virus-host interactions and identify host factors contributing to viral pathogenesis and disease progression. In this study, we perform a genome-wide CRISPR knockout screen using HCoV-229E and identify UHRF1 as a potent restriction factor. Mechanistically, UHRF1 suppresses HCoV-229E infection by downregulating the expression of its cell entry receptor, APN, through promoter hypermethylation. Focused CRISPR activation screens of UHRF1-downregulated genes confirm the critical role of APN in HCoV-229E infection and identify additional genes (e.g., SIGLEC1, PLAC8, and heparan sulfate biosynthesis genes) contributing to the restrictive functions of UHRF1. Transcriptomic and single-cell RNA sequencing analysis reveal that UHRF1 expression decreases with age, negatively correlating with increased APN expression. This age-related decline in UHRF1 is validated in primary alveolar macrophages from elderly individuals, which exhibit heightened susceptibility to HCoV-229E compared to those from younger individuals. Our findings highlight UHRF1 as a key age-related host defense factor against coronavirus and provide insights into the epigenetic regulation of viral entry receptors.

Indexed as

CCAAT-Enhancer-Binding ProteinsCoronavirus 229E, HumanCoronavirus InfectionsReceptors, VirusUbiquitin-Protein LigasesAnimalsDNA MethylationDown-RegulationEpigenesis, GeneticGene SilencingHEK293 CellsHost-Pathogen InteractionsHumansPromoter Regions, GeneticCCAAT-Enhancer-Binding ProteinsReceptors, VirusUbiquitin-Protein LigasesUHRF1 protein, human

Identifiers

PMID41253770
PMCPMC12627610

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.