Evidence map›Paper›PMID 37428471›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023

Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression.

Wenbin Liu, Yue Zhao, Junyan Fan, Jiaying Shen, Hailin Tang, Wanda Tang, Di Wu, Weijin Huang, Yibo Ding, Peng Qiao and 11 more

Open access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A survey of SARS-CoV-2 tropism.Infectious diseases & immunity · 2025
    Review
  5. Review
  6. Genetic variants inFrontiers in genetics · 2025
    Article
  7. Article
  8. 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

21 authors at 7 institutions in 3 countries.

Wenbin LiuKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Yue ZhaoKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Junyan FanKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Jiaying ShenShanghai Key Laboratory of Medical Biodefense, Shanghai, 200433, China.
Hailin TangShanghai Key Laboratory of Medical Biodefense, Shanghai, 200433, China.
Wanda TangShanghai Key Laboratory of Medical Biodefense, Shanghai, 200433, China.
Di WuSeven Plus Technology Company Limited, Tianjin, 300301, China.
Weijin HuangInstitute for Biological Product Control, National Institutes for Food and Drug Control, WHO Collaborating Center for Standardization and Evaluation of Biologicals, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products and NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, 102629, China.
Yibo DingKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Peng QiaoDepartment of Infectious Disease Control, Center for Disease Control and Prevention of Yangpu District, Shanghai, 200090, China.
Jiansheng LinDepartment of Epidemiology, School of Medicine, Jinan University, Guangzhou, China.
Zishuai LiKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Qianqian LiInstitute for Biological Product Control, National Institutes for Food and Drug Control, WHO Collaborating Center for Standardization and Evaluation of Biologicals, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products and NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, 102629, China.
Qianqian CuiInstitute for Biological Product Control, National Institutes for Food and Drug Control, WHO Collaborating Center for Standardization and Evaluation of Biologicals, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products and NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, 102629, China.
Yan LiuKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Yifan ChenKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Rui PuKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Xue HanDepartment of Infectious Disease Control, Center for Disease Control and Prevention of Yangpu District, Shanghai, 200090, China.
Jianhua YinKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Xiaojie TanKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.
Guangwen CaoKey Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China.ORCID 0000-0002-8094-1278
Ministry of Defence · GBNational Medical Products Administration · CNSecond Military Medical University · CNTaiwan Centers for Disease Control · TWTongji University · CNJinan University · CNTianjin Economic-Technological Development Area · CN

Funding

National Key Research and Development Program of China 2022YFC2602900National Natural Science Foundation of China 82041022Scientific Research Project of Shanghai Municipal Health Commission 20204Y0304Scientific Research Project of Shanghai Science and Technology Commission 20431900404Scientific Research Project of Shanghai Science and Technology Commission 20JC1410202Shanghai Yangfan Program 20YF1458800
6 · The paper itself

Abstract

Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its binding of NR4A2 to their promoters, which is independent of functional genetic polymorphisms in ACE2 and TMPRSS2. Benzo[a]pyrene increases the susceptibility of lung epithelial cells to SARS-CoV-2 pseudoviruses and facilitates the infection of authentic Omicron BA.5 in primary human alveolar type II cells, lung organoids, and lung and testis of hamsters. Increased expression of Nr4a2, Ace2, and Tmprss2, as well as decreased methylation of CpG islands at the Nr4a2 promoter are observed in aged mice compared to their younger counterparts. NR4A2 knockdown or interferon-λ2/λ3 stimulation downregulates the expression of NR4A2, ACE2, and TMPRSS2, thereby inhibiting the infection. In conclusion, benzo[a]pyrene enhances SARS-CoV-2 infection by boosting NR4A2-induced ACE2 and TMPRSS2 expression. This study elucidates the mechanisms underlying the detrimental effects of cigarette smoking on SARS-CoV-2 infection and provides prophylactic options for coronavirus disease 2019, particularly for the elderly population.

Indexed as

COVID-19AgedAngiotensin-Converting Enzyme 2AnimalsBenzo(a)pyreneHumansLungMaleMiceNuclear Receptor Subfamily 4, Group A, Member 2SARS-CoV-2Serine EndopeptidasesAngiotensin-Converting Enzyme 2Benzo(a)pyreneNR4A2 protein, humanNuclear Receptor Subfamily 4, Group A, Member 2Serine EndopeptidasesTMPRSS2 protein, humanangiotensin-converting enzyme 2cigarettescoronavirus disease 2019NR4A2transmembrane protease serine 2

Identifiers

PMID37428471
PMCPMC10502855
OpenAlexW4383710148

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.