颗粒物暴露加重了人源化ACE2小鼠对SARS-CoV-2感染的易感性

Teng-Yu Zhu; Huan Qiu; Qi-Qi Cao; Zi-Lei Duan; Feng-Liang Liu; Tian-Zhang Song; Yang Liu; Ya-Qun Fang; Guang-Ming Wu; Yong-Tang Zheng; Wen-Jun Ding; Ren Lai; Lin Jin

doi:10.24272/j.issn.2095-8137.2021.088

颗粒物暴露加重了人源化ACE2小鼠对SARS-CoV-2感染的易感性

doi: 10.24272/j.issn.2095-8137.2021.088

祝腾宇^{1, 2, 3, 6, #},
邱欢^{2, 3, #},
曹奇奇^{1, #},
段自磊^{2, 6, #},
刘丰亮²,
宋天章²,
刘洋^{2, 3},
房亚群^{2, 6},
吴光明⁴,
郑永唐^{2, 6},
丁文军^5, ,,
赖仞^{1, 2, 6},
靳林^{2, 6, #, ,}

1.
南京农业大学生命科学学院，江苏南京 210095，中国
2.
中国科学院昆明动物研究所中国科学院动物模型与人类疾病机理重点实验室/云南省生物活性肽重点实验室，云南昆明 650223，中国
3.
中国科学院大学昆明生命科学学院，云南昆明 650204，中国
4.
生物家园实验室细胞谱系与图谱中心，广东广州 510530，中国
5.
中国科学院大学环境与健康实验室，北京 100049，中国
6.
中国科学院昆明动物研究所国家昆明高等级生物安全灵长类动物实验中心，云南昆明 650107，中国

计量
- 文章访问数: 1363
- HTML全文浏览量: 706
- PDF下载量: 541
- 被引次数: 0
出版历程
- 收稿日期: 2021-03-19
- 录用日期: 2021-04-09
- 网络出版日期: 2021-05-08
- 刊出日期: 2021-05-18

Particulate matter exposure exacerbates susceptibility to SARS-CoV-2 infection in humanized ACE2 mice

Teng-Yu Zhu^{1, 2, 3, 6, #},
Huan Qiu^{2, 3, #},
Qi-Qi Cao^{1, #},
Zi-Lei Duan^{2, 6, #},
Feng-Liang Liu²,
Tian-Zhang Song²,
Yang Liu^{2, 3},
Ya-Qun Fang^{2, 6},
Guang-Ming Wu⁴,
Yong-Tang Zheng^{2, 6},
Wen-Jun Ding^{5
, ,},
Ren Lai^{1, 2, 6},
Lin Jin^{2, 6, #
, ,}

1.
College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China
2.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
3.
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
4.
Centre for Cell Lineage and Atlas, Bioland Laboratory, Guangzhou, Guangdong 510530, China
5.
Laboratory of Environment and Health, University of Chinese Academy of Sciences, Beijing 100049, China
6.
Kunming National High-level Biosafety Research Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China

Funds: This work was supported by the National Natural Science Foundation of China (NSFC) (31900331, 32070444), Science and Technology Department of Yunnan Province (202001AW070019), Chinese Academy of Sciences “Light of West China” Program and Youth Innovation Promotion Association (2019378) to L.J. and the NSFC (21761142002), Chinese Academy of Sciences (XDB31000000, SAJC201606 and KGFZD-135-17-011), and Yunnan Province (2019-YT-053 and 2019ZF003) to R.L. and the NSFC (91643206) to W.J.D

More Information

Corresponding author: E-mail: dingwj@ucas.ac.cn; jinlin@mail.kiz.ac.cn

#Authors contributed equally to this work

摘要

摘要: 由严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2)引起的2019冠状病毒病在全球爆发，全球感染人数超过1.5亿，死亡327万人。有证据表明，可在大气颗粒物(PM)上检测到SARS-CoV-2 的RNA, COVID-19病例与空气污染物水平相关。然而，PM参与SARS-CoV-2传播的机制仍然鲜为人知。我们发现PM暴露增加了一些上皮细胞血管紧张素转换酶2 (angiotensin-converting enzyme 2, ACE2)和跨膜丝氨酸蛋白酶2 (transmembrane serine protease 2, TMPRSS2)的表达水平，并增加了SARS-CoV-2刺突蛋白的吸附。在hACE2小鼠模型中灌注PM显著增加了肺中ACE2和Tmpss2的表达和病毒的复制。此外，PM加重了hACE2小鼠中SARS-CoV-2感染引起的肺部病变。综上所述，我们的研究表明，PM是COVID-19的一个流行因素，强调了佩戴防PM口罩应对这场全球大流行的必要性。
- COVID-19 /
- 颗粒物 /
- 流行风险 /
- hACE2小鼠 /
- SARS-CoV-2进入因子
Abstract: The global outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of 8 May 2021, has surpassed 150 700 000 infections and 3 279 000 deaths worldwide. Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter (PM), and COVID-19 cases are correlated with levels of air pollutants. However, the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood. Here, we found that PM exposure increased the expression level of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein. Instillation of PM in a hACE2 mouse model significantly increased the expression of ACE2 and Tmprss2 and viral replication in the lungs. Furthermore, PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice. In conclusion, our study demonstrated that PM is an epidemiological factor of COVID-19, emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.
- COVID-19 /
- Particulate matter /
- Epidemic risk /
- hACE2 mice /
- SARS-CoV-2 entry factor
#Authors contributed equally to this work
注释:

HTML全文

Figure 1. PM exposure induces ACE2 and TMPRSS2 expression and elevates susceptibility of hACE2 mice to SARS-CoV-2 infection

A: Immunofluorescence analysis of adsorption spike protein of SARS-CoV-2 after 200 μg/mL PM administration for 24 h. Scale bars: 100 μm. B: Quantitative PCR (qPCR) analysis of ACE2 and TMPRSS2 in HPAEpiC cells after 50 or 200 μg/mL PM administration for 24 h. C: Immunoblot analysis of ACE2 and TMPSSR2 in HPAEpiC cells after 50 or 200 μg/mL PM administration for 24 h. GAPDH was used as the loading control. D: Congestion in lungs of SARS-CoV-2-infected hACE2 mice with or without exposure to PM. Scale bars: 50 μm. E: qPCR analysis of relative viral loads and expression of ACE2 and Tmprss2 in two left pulmonary lobes of mice. F: Immunofluorescence staining of SARS-CoV-2 spike protein and human ACE2 in left lungs of SARS-CoV-2-infected hACE2 mice at 3 dpi. Scale bars: 100 μm. G: qPCR analysis of Il6, Tnfa, Il2, and Il1b genes in SARS-CoV-2-infected hACE2 mice; results are presented relative to those of mouse Hprt. Data are mean±standard error of the mean (SEM).

下载: 全尺寸图片幻灯片

参考文献(9)

[1]	Fattorini D, Regoli F. 2020. Role of the chronic air pollution levels in the Covid-19 outbreak risk in Italy. Environmental Pollution, 264: 114732.
[2]	Fronza R, Lusic M, Schmidt M, Lucic B. 2020. Spatial-temporal variations in atmospheric factors contribute to SARS-CoV-2 outbreak. Viruses, 12(6): 588. doi: 10.3390/v12060588
[3]	Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis G, van Goor H. 2004. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. Journal of Pathology, 203(2): 631−637.
[4]	Kim JH, Kim J, Kim WJ, Choi YH, Yang SR, Hong SH. 2020. Diesel particulate matter 2.5 induces epithelial-to-mesenchymal transition and upregulation of SARS-CoV-2 receptor during human pluripotent stem cell-derived alveolar organoid developmen. International Journal of Environmental Research and Public Health, 17(22): 8410. doi: 10.3390/ijerph17228410
[5]	Liu FL, Wu KX, Sun JY, Duan ZL, Quan XZ, Kuang JQ, et al. 2021. Rapid generation of ACE2 humanized inbred mouse model for COVID-19 with tetraploid complementation. National Science Review, 8(2): nwaa285.
[6]	Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F. 2010. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. Journal of Virology, 84(24): 12658−12664. doi: 10.1128/JVI.01542-10
[7]	Smith JC, Sausville EL, Girish V, Yuan ML, Vasudevan A, John KM, et al. 2020. Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract. Developmental Cell, 53(5): 514−529.e3. doi: 10.1016/j.devcel.2020.05.012
[8]	Zhu N, Zhang DY, Wang WL, Li XW, Yang B, Song JD, et al. 2020. A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine, 382(8): 727−733. doi: 10.1056/NEJMoa2001017
[9]	Zoran MA, Savastru RS, Savastru DM, Tautan MN. 2020. Assessing the relationship between surface levels of PM_2.5 and PM10 particulate matter impact on COVID-19 in Milan, Italy. Science of The Total Environment, 738: 139825. doi: 10.1016/j.scitotenv.2020.139825

计量

文章访问数: 1363
HTML全文浏览量: 706
PDF下载量: 541
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

颗粒物暴露加重了人源化ACE2小鼠对SARS-CoV-2感染的易感性

doi: 10.24272/j.issn.2095-8137.2021.088

计量

Particulate matter exposure exacerbates susceptibility to SARS-CoV-2 infection in humanized ACE2 mice

Corresponding author: E-mail: dingwj@ucas.ac.cn; jinlin@mail.kiz.ac.cn

计量

目录

在线期刊

作者中心

关于本刊

留言板

颗粒物暴露加重了人源化ACE2小鼠对SARS-CoV-2感染的易感性

doi: 10.24272/j.issn.2095-8137.2021.088

计量

出版历程

Particulate matter exposure exacerbates susceptibility to SARS-CoV-2 infection in humanized ACE2 mice

Corresponding author: E-mail: dingwj@ucas.ac.cn; jinlin@mail.kiz.ac.cn

计量

出版历程

目录

在线期刊

作者中心

关于本刊