High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa

Abstract

It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.

References

[1] Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet, 2020, 395: 470-473.

[2] Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol., 2013, 30: 772-780.

[3] Wang, D. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. https://jamanetwork.com/journals/jama/fullarticle/2761044 (2020).

[4] Zhou P, . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature., 2020

[5] Zhu, N. et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. https://www.nejm.org/doi/full/10.1056/NEJMoa2001017 (2020).

[6] Lu R, . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020

[7] Li W, . Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003, 426: 450-454.

[8] Hofmann H, . Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc. Natl Acad. Sci. USA, 2005, 102: 7988-7993.

[9] Xu X, . Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci. China Life Sci., 2020

[10] Zou, X. et al. The single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019-nCoV infection. Front. Med. http://journal.hep.com.cn/fmd/EN/10.1007/s11684-020-0754-0 (2020).

[11] Zhao, Y. et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. Preprint at https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1 (2020).

[12] Zhang, H. et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. Preprint at https://www.biorxiv.org/content/10.1101/2020.01.30.927806v1 (2020).

[13] Chai, X. et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. Preprint at https://www.biorxiv.org/content/10.1101/2020.02.03.931766v1 (2020).

[14] de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol., 2016, 14: 523-534.

[15] Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J. Med. Virol., 2020

[16] Ren X, . Analysis of ACE2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome-associated coronavirus. J. Gen. Virol., 2006, 87: 1691-1695.

[17] Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett., 2002, 532: 107-110.

[18] Hamming I, . Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol., 2004, 203: 631-637.

[19] Rostom R, Svensson V, Teichmann SA, Kar G. Computational approaches for interpreting scRNA-seq data. FEBS Lett., 2017, 591: 2213-2225.

[20] Guan, W.-J. et al. Clinical characteristics of 2019 novel coronavirus infection in China. Preprint at https://www.medrxiv.org/content/10.1101/2020.02.06.20020974v1 (2020).

[21] Peixoto AP, Campos GS, Queiroz LB, Sardi SI. Asymptomatic oral human papillomavirus (HPV) infection in women with a histopathologic diagnosis of genital HPV. J. Oral Sci., 2011, 53: 451-459.

[22] Dionne KR, Warnakulasuriya S, Zain RB, Cheong SC. Potentially malignant disorders of the oral cavity: current practice and future directions in the clinic and laboratory. Int. J. Cancer, 2015, 136: 503-515.

[23] Li J, . Associations between proteasomal activator PA28γ and outcome of oral squamous cell carcinoma: evidence from cohort studies and functional analyses. EBioMedicine, 2015, 2: 851-858.

[24] Wang Z, . RACK1, an excellent predictor for poor clinical outcome in oral squamous carcinoma, similar to Ki67. Eur. J. Cancer, 2009, 45: 490-496.

[25] Forrest, A. R. et al. A promoter-level mammalian expression atlas. Nature 507, 462–470 (2014).

Funding

111 Project of MOE,B14038