Smoke and Spike: Benzo (a) pyrene Enhances SARS‐CoV‐2 Infection by Boosting NR4A2‐Induced ACE2 and TMPRSS2 Expression
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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Smoke and Spike: Benzo (a) pyrene Enhances SARS‐CoV‐2 Infection by Boosting NR4A2‐Induced ACE2 and TMPRSS2 Expression ; day:10 ; month:07 ; year:2023 ; extent:16
Advanced science ; (10.07.2023) (gesamt 16)
- Urheber
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Liu, Wenbin
Zhao, Yue
Fan, Junyan
Shen, Jiaying
Tang, Hailin
Tang, Wanda
Wu, Di
Huang, Weijin
Ding, Yibo
Qiao, Peng
Lin, Jiansheng
Li, Zishuai
Li, Qianqian
Cui, Qianqian
Liu, Yan
Chen, Yifan
Pu, Rui
Han, Xue
Yin, Jianhua
Tan, Xiaojie
Cao, Guangwen
- DOI
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10.1002/advs.202300834
- URN
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urn:nbn:de:101:1-2023071115035031346670
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:47 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Liu, Wenbin
- Zhao, Yue
- Fan, Junyan
- Shen, Jiaying
- Tang, Hailin
- Tang, Wanda
- Wu, Di
- Huang, Weijin
- Ding, Yibo
- Qiao, Peng
- Lin, Jiansheng
- Li, Zishuai
- Li, Qianqian
- Cui, Qianqian
- Liu, Yan
- Chen, Yifan
- Pu, Rui
- Han, Xue
- Yin, Jianhua
- Tan, Xiaojie
- Cao, Guangwen
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