Expression Pattern of the SARS-CoV-2 Entry Genes and in the Respiratory Tract

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2020 Oct 21

PMID 33081421

Citations 22

Authors

Yichuan Liu

Hui-Qi Qu

Jingchun Qu

Lifeng Tian

Hakon Hakonarson

Affiliations

Soon will be listed here.

Abstract

To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease TMPRSS2 in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. The expression of ACE2 is low in mucosal-associated invariant T (MAIT) cells and cannot be detected in alveolar macrophages. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium and has lower expression in masticatory mucosa. Our results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and consequently for subsequent droplet transmission and should be the focus for protection against SARS-CoV-2 infection.

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References

Wu Z, McGoogan J . Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323(13):1239-1242. DOI: 10.1001/jama.2020.2648. View

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

Bunyavanich S, Do A, Vicencio A . Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults. JAMA. 2020; 323(23):2427-2429. PMC: 7240631. DOI: 10.1001/jama.2020.8707. View

Li W, Moore M, Vasilieva N, Sui J, Wong S, Berne M . Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965):450-4. PMC: 7095016. DOI: 10.1038/nature02145. View

Ziegler C, Allon S, Nyquist S, Mbano I, Miao V, Tzouanas C . SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020; 181(5):1016-1035.e19. PMC: 7252096. DOI: 10.1016/j.cell.2020.04.035. View

Millet J, Whittaker G . Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2014; 202:120-34. PMC: 4465284. DOI: 10.1016/j.virusres.2014.11.021. View

Huentelman M, Zubcevic J, Hernandez Prada J, Xiao X, Dimitrov D, Raizada M . Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension. 2004; 44(6):903-6. DOI: 10.1161/01.HYP.0000146120.29648.36. View

Cai G, Bosse Y, Xiao F, Kheradmand F, Amos C . Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med. 2020; 201(12):1557-1559. PMC: 7301735. DOI: 10.1164/rccm.202003-0693LE. View

Liu Y, Gayle A, Wilder-Smith A, Rocklov J . The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020; 27(2). PMC: 7074654. DOI: 10.1093/jtm/taaa021. View

10.

Liao Y, Li X, Mou T, Zhou X, Li D, Wang L . Distinct infection process of SARS-CoV-2 in human bronchial epithelial cell lines. J Med Virol. 2020; 92(11):2830-2838. PMC: 7323243. DOI: 10.1002/jmv.26200. View

11.

Lukassen S, Chua R, Trefzer T, Kahn N, Schneider M, Muley T . SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020; 39(10):e105114. PMC: 7232010. DOI: 10.15252/embj.20105114. View

12.

Lescure F, Bouadma L, Nguyen D, Parisey M, Wicky P, Behillil S . Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. 2020; 20(6):697-706. PMC: 7156120. DOI: 10.1016/S1473-3099(20)30200-0. View

13.

Zou X, Chen K, Zou J, Han P, Hao J, Han Z . Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020; 14(2):185-192. PMC: 7088738. DOI: 10.1007/s11684-020-0754-0. View

14.

Richter G, Kruppa J, Munz M, Wiehe R, Hasler R, Franke A . A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers. Clin Epigenetics. 2019; 11(1):105. PMC: 6647091. DOI: 10.1186/s13148-019-0697-y. View

15.

Latini A, Agolini E, Novelli A, Borgiani P, Giannini R, Gravina P . COVID-19 and Genetic Variants of Protein Involved in the SARS-CoV-2 Entry into the Host Cells. Genes (Basel). 2020; 11(9). PMC: 7565048. DOI: 10.3390/genes11091010. View

16.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

17.

Wolfel R, Corman V, Guggemos W, Seilmaier M, Zange S, Muller M . Virological assessment of hospitalized patients with COVID-2019. Nature. 2020; 581(7809):465-469. DOI: 10.1038/s41586-020-2196-x. View

18.

Chang L, Yan Y, Wang L . Coronavirus Disease 2019: Coronaviruses and Blood Safety. Transfus Med Rev. 2020; 34(2):75-80. PMC: 7135848. DOI: 10.1016/j.tmrv.2020.02.003. View

19.

Ferrario C, Ahmad S, Nagata S, Simington S, Varagic J, Kon N . An evolving story of angiotensin-II-forming pathways in rodents and humans. Clin Sci (Lond). 2013; 126(7):461-9. PMC: 4280795. DOI: 10.1042/CS20130400. View

20.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View