Preview

Medical and Biological Problems of Life Activity

Advanced search

A comparative analysis of the expression of key proteins involved in the entry of coronavirus into different types of cell cultures

https://doi.org/10.58708/2074-2088.2025-3(35)-27-33

Abstract

The expression of specific receptors and proteases in each cell type determines the relative preference for different modes of SARS-CoV-2 entry. This includes entry through TMPRSS2-mediated fusion of the viral and host cell membranes, as well as entry through endocytosis, which involves the activity of cathepsin L. Cathepsin L is responsible for cleaving the viral S protein, and its expression level can affect the efficiency of viral entry. The expression level of mRNA for three key proteins involved in SARS CoV-2 entry into host cells (ACE2 receptor, TMPRSS2 serine protease, and cathepsin L) was assessed in human cell lines from various tissues (n=5), and in cell lines derived from the kidneys of different animal species (n=7). The highest level of ACE2 gene expression was observed in the human colon adenocarcinoma cell line Caco-2, and in the Vero and VeroE6 cells (derived from African green monkey kidneys), the expression of this gene was more than four times higher than in the other studied animal cell lines. Among human cell lines, the highest level of TMPRSS2 gene expression was observed in HEK293T (embryonic kidney) and Caco-2 cells, and among animal cell cultures, it was seen in MDBK (domestic bovine kidney) cells. The maximum level of CTSL mRNA expression was found in A549 (human lung cancer) cells. These findings are important for selecting a model system to study the pathways used by the virus to enter target cells and to investigate various aspects of SARS-CoV-2’s interaction with cells.

About the Authors

E. G. Fomina
ГУ «РЦ гигиены, эпидемиологии и общественного здоровья»
Belarus


E. E. Grigorieva
ГУ «РЦ гигиены, эпидемиологии и общественного здоровья»
Belarus


V. V. Zverko
ГУ «РЦ гигиены, эпидемиологии и общественного здоровья»
Belarus


A. D. Korzheeva
ООО «Альгимед Техно»
Belarus


References

1. Izaguirre, G. The proteolytic regulation of virus cell entry by furin and other proprotein convertases / G. Izaguirre // Viruses. – 2019. – Vol. 11, no. 9. – P. 837.

2. The role of cysteine peptidases in coronavirus cell entry and replication: the therapeutic potential of cathepsin inhibitors / A. Pišlar [et al.] // PLoS Pathog. – 2020. – Vol. 16, no. 11. e1009013.

3. Mechanisms of SARS-CoV-2 entry into cells / C.B. Jackson [et al.] // Nat. Rev. Mol. Cell Biol. – 2022. – Vol. 23, no. 1. – P. 3-20.

4. Human immunodeficiency viruses pseudotyped with SARS-CoV-2 spike proteins infect a broad spectrum of human cell lines through multiple entry mechanisms / C. Xu [et al.] // Viruses. – 2021. – Vol. 13, no. 6. – P. 953.

5. The SARS-CoV-2 spike protein has a broad tropism for mammalian ACE2 proteins / C. Conceicao [et al.] // PLoS Biol. – 2020. – Vol. 18, no. 12. e3001016.

6. SARS-CoV-2 pseudovirus infectivity and expression of viral entry-related factors ACE2, TMPRSS2, Kim-1, and NRP-1 in human cells from the respiratory, urinary, digestive, reproductive, and immune systems / F. Zhang [et al.] // J. Med. Virol. – 2021. – Vol. 93. – P. 6671-6685.

7. Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development / M. Zhao [et al.] // Signal Transduct. Target Ther. – 2021. – Vol. 6, no. 1. – P. 134.

8. A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells / Y. Wang [et al.] // Int. J. Med. Sci. – 2020. – Vol. 17, no. 11. – P. 1522-1531.

9. Evaluating angiotensin-converting enzyme 2-mediated SARS-CoV-2 entry across species / H-L. Zhang [et al.] // J. Biol. Chem. – 2021. – Vol. 296. – P. 100435.

10. Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation / B. Fraser [et al.] // Nat. Chem. Biol. – 2022. – Vol. 18, no. 9. – P. 963-971.

11. Wettstein, L. The transmembrane protease TMPRSS2 as a therapeutic target for COVID-19 treatment / L. Wettstein, F. Kirkhoff, J. Munch // Int. J. Mol. Sci. – 2022. – Vol. 23, no. 3. – P. 1351.

12. Huang, C. Comparative analyses of ACE2 and TMPRSS2 gene: implications for the risk to which vertebrate animals are susceptible to SARS-CoV-2 / C. Huang, Y. Jiang, J. Yang // J. Med. Virol. – 2021. – Vol. 93, no. 9. – P. 5487-5504.

13. Berdowska, I. Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis – with impact on gastrointestinal tract / I. Berdowska, M. Matusiewicz // World J. Gastroenterol. – 2021. – Vol. 27, no. 39. – P. 6590-6600.

14. The genome landscape of the african green monkey kidney-derived Vero cell line / N. Osada [et al.] // DNA Res. – 2014. – Vol. 21, no. 6. – P. 673-683. 15. Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile / N. Wurtz [et al.] // Eur. J. Clin. Microbiol. Infect. Dis. – 2021. – Vol. 40, no. 3. – P. 477-484.

15. Culture of SARS-CoV-2 in a panel of laboratory cell lines, permissivity, and differences in growth profile / N. Wurtz [et al.] // Eur. J. Clin. Microbiol. Infect. Dis. – 2021. – Vol. 40, no. 3. – P. 477-484

16.


Supplementary files

Review

For citations:


Fomina E.G., Grigorieva E.E., Zverko V.V., Korzheeva A.D. A comparative analysis of the expression of key proteins involved in the entry of coronavirus into different types of cell cultures. Medical and Biological Problems of Life Activity. 2025;(3):27-33. (In Russ.) https://doi.org/10.58708/2074-2088.2025-3(35)-27-33

Views: 4


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2088 (Print)