1. Please check and comment entries here.
Table of Contents

    Topic review

    Expression of SARS-CoV-2 Entry Genes

    Subjects: Others
    View times: 72
    Submitted by:

    Definition

    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. TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium and has lower expression in masticatory mucosa. These results provide the molecular basis that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection.

    1. SARS-CoV-2 Entry Genes in human airway and oral mucosa

    The human angiotensin-I-converting enzyme 2 (ACE2) has been suggested to serve as the receptor for the cell entry of SARS-CoV-2 to cause infection [1]. ACE2 is a member of the renin–angiotensin system (RAS), with the function of converting angiotensin II to angiotensin-(1-7) (with seven amino acids), and converting angiotensin I to angiotensin-(1-9) [2], thereby negatively regulating the effects of angiotensin-I-converting enzyme (ACE) and the RAS system. In addition to its critical roles in RAS, ACE2 binds the S1 domain of the SARS-CoV Spike (S) protein as the viral receptor, and accounts for the infection of SARS-CoV and syncytia formation [3]. The genome sequence of SARS-CoV-2 shows significant similarity (79%) to that of SARS-CoV, while its receptor-binding domain shows even higher similarity to that of SARS-CoV [1], further supporting ACE2 as the receptor of SARS-CoV-2. After binding with ACE2, SARS-CoV-2 priming by the serine protease encoded by the transmembrane serine protease 2 gene (TMPRSS2) is also required for the viral entry into host cells [4][5]. Knowledge about the expression of ACE2 and TMPRSS2 is extremely important to understand the infection of SARS-CoV-2 and to find ways to prevent the infection.

    2. RNA sequencing transcriptome profiling of samples of airway and oral mucosa

    This study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa, including small airway epithelium, alveolar macrophages, nasal epithelium, and masticatory mucosa.  As shown by the results, 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. This study highlights that the nasal mucosa is the most susceptible locus in the respiratory tract for SARS-CoV-2 infection and replication, is responsible for the subsequent high level of droplet transmission. More details seen in https://www.mdpi.com/1999-4915/12/10/1174  

    Figure 1. The expression of ACE, ACE2, and TMPRSS2 in five different types of samples. Y-axis represents FPKM values.

    Figure 1. The expression of ACE, ACE2, and TMPRSS2 in five different types of samples. Y-axis represents FPKM values.

     

    The entry is from 10.3390/v12101174

    References

    1. Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020, 395, 565–574.
    2. Ferrario, C.M.; Ahmad, S.; Nagata, S.; Simington, S.W.; Varagic, J.; Kon, N.; Dell’italia, L.J. An evolving story of angiotensin-II-forming pathways in rodents and humans. Clin. Sci. 2014, 126, 461–469.
    3. Li, W.; Moore, M.J.; Vasilieva, N.; Sui, J.; Wong, S.K.; Berne, M.A.; Somasundaran, M.; Sullivan, J.L.; Luzuriaga, K.; Greenough, T.C. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426, 450–454.
    4. Lukassen, S.; Chua, R.L.; Trefzer, T.; Kahn, N.C.; Schneider, M.A.; Muley, T.; Winter, H.; Meister, M.; Veith, C.; Boots, A.W. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020, 39, e105114.
    5. Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.-H.; Nitsche, A. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020, 181, 271–280.e8.
    More