ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal-Oral Routes

Mei Zhong; Bingpeng Lin; Janak L Pathak; Hongbin Gao; Andrew J Young; Xinhong Wang; Chang Liu; Kaibin Wu; Mingxiao Liu; Jian-Ming Chen; Jiangyong Huang; Learn-Han Lee; Cui-Ling Qi; Linhu Ge; Lijing Wang

doi:10.3389/fmed.2020.580796

ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal-Oral Routes

Front Med (Lausanne). 2020 Dec 10:7:580796. doi: 10.3389/fmed.2020.580796. eCollection 2020.

Authors

Mei Zhong¹, Bingpeng Lin¹, Janak L Pathak^{1

2}, Hongbin Gao³, Andrew J Young⁴, Xinhong Wang¹, Chang Liu⁵, Kaibin Wu¹, Mingxiao Liu¹, Jian-Ming Chen¹, Jiangyong Huang¹, Learn-Han Lee⁶, Cui-Ling Qi⁷, Linhu Ge^{1

2}, Lijing Wang^{1

7}

Affiliations

¹ Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, China.
² Institute of Oral Disease, Guangzhou Medical University, Guangzhou, China.
³ Key Laboratory of Guangdong Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.
⁴ Columbus Inpatient Care, Grove City, OH, United States.
⁵ Stomatology School of Ji'nan University, Guangzhou, China.
⁶ Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia.
⁷ School of Life Science and Biopharmaceutics, Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.

Abstract

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear. Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level. Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results. Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal-oral routes.

Keywords: ACE2 (angiotensin converting enzyme-2); COVID-19; Furin; SARS-CoV-2; oral mucosa; single cell RNA seq.