Increasing host cellular receptor—angiotensin‐converting enzyme 2 expression by coronavirus may facilitate 2019‐nCoV (or SARS‐CoV‐2) infection

• Published in: Journal of medical virology Vol. 92; no. 11; pp. 2693 - 2701
• Main Authors: Zhuang, Meng‐Wei, Cheng, Yun, Zhang, Jing, Jiang, Xue‐Mei, Wang, Li, Deng, Jian, Wang, Pei‐Hui
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2020; John Wiley and Sons Inc
• Subjects: 2019‐nCoV; ACE2; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - immunology; Conversion; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - virology; Cytokines; Disease transmission; Drug delivery; Enzymes; Epidemics; Gene Expression; Health risks; HEK293 Cells; Humans; IFN; Infections; Infectious diseases; Inflammation; Interferon; Interferons - pharmacology; ISG; Microarray Analysis; Protein Binding; Proteins; Public health; Receptors; Receptors, Virus - genetics; Receptors, Virus - immunology; Respiratory diseases; Ribonucleic acid; Risk analysis; Risk factors; RNA; SARS Virus - genetics; SARS Virus - pathogenicity; SARS-CoV-2 - genetics; SARS-CoV-2 - pathogenicity; SARS‐CoV‐2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Up-Regulation; Viral diseases; Virology; Viruses; COVID-19; IFN; ACE2; SARS-CoV-2; 2019-nCoV; ISG
• ISSN: 0146-6615; 1096-9071; 1096-9071
• DOI: 10.1002/jmv.26139

The ongoing outbreak of a new coronavirus (2019‐nCoV, or severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) has caused an epidemic of the acute respiratory syndrome known as coronavirus disease (COVID‐19) in humans. SARS‐CoV‐2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS‐CoV‐1 and SARS‐CoV‐2 may use the same host cellular receptor, angiotensin‐converting enzyme 2 (ACE2), for entering host cells. The affinity between ACE2 and the SARS‐CoV‐2 S protein is much higher than that of ACE2 binding to the SARS‐CoV S protein, explaining why SARS‐CoV‐2 seems to be more readily transmitted from human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS‐CoV‐1 and SARS‐CoV‐2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS‐CoV‐2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high‐risk factors for developing COVID‐19, and the infection of other viruses may increase the risk of SARS‐CoV‐2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses. Highlights Virus infection and inflammatory cytokines can stimulate angiotensin‐converting enzyme 2 (ACE2) expression. ACE2 is upregulated by the activation of RNA‐sensing pathways. ACE2 is a novel interferon‐stimulated gene (ISG). The increase in ACE2 induced by various viruses and inflammatory cytokines may facilitate severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and spreading.