Independent Tendency of ACE2 and GRP78 Expression in SARS-CoV2 Infection
DOI:
https://doi.org/10.18196/mmjkk.v22i2.14731Keywords:
gene expression, ACE2, GRP78, SARS-CoV2Abstract
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is a virus that attacks the respiratory tract and causes the COVID-19 pandemic. This virus utilizes the host receptor as a cellular entry. Angiotensin-converting enzyme 2 (ACE2) has been assumed to be the essential host receptor for SARS-CoV2 infection. Furthermore, another costimulatory molecule, such as glucose-related protein 78 (GRP78), has also been reported. However, there are several inconsistent clinical data that could be observed regarding these molecules' involvement during SARS-CoV2 infection. This study aims to observe the possible involvement of ACE2 and GRP78 during the infection phase through gene expression profile analysis. Clinical specimens used in this study were taken in positive and negative clinical samples after the standard swab sampling procedure from both oropharyngeal and nasopharyngeal swabs. Subsequently, nucleic acid samples were proceeded by conventional Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) to analyze the expression of ACE2 and GRP78. Agarose gel electrophoresis was then performed before the densitometric analysis. Statistical analysis using Mann-Whitney Test and Independent Sample t-Test was applied to justify the gene profile difference between ACE2 and GRP78. Our study suggested the enhancement tendency while they were not statistically significant in both ACE2 and GRP78 expression from the positive SARS-CoV2 samples.References
Ludwig S, Zarbock A. Coronaviruses and SARS-CoV-2: A Brief Overview. Anesth Analg. 2020;131(1):93–6. https://doi.org/10.1213/ANE.0000000000004845
Li M-Y, Li L, Zhang Y, Wang X-S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020;9(1):45. https://doi.org/10.1186/s40249-020-00662-x
Peng X, Xu X, Li Y, Cheng L, Zhou X, Ren B. Transmission routes of 2019-nCoV and controls in dental practice. Int J Oral Sci. 2020;12(1):9. https://doi.org/10.1038/s41368-020-0075-9
Wang L, Wang Y, Ye D, Liu Q. Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence. Int J Antimicrob Agents. 2020;55(6):1–8. https://doi.org/10.1016/j.ijantimicag.2020.105948
Rossi GA, Sacco O, Mancino E, Cristiani L, Midulla F. Differences and similarities between SARS‑CoV and SARS‑CoV‑2 spike receptor‑binding domain recognition and host cell infection with support of cellular serine proteases. Infection. 2020;(48):665–9. https://doi.org/10.1007/s15010-020-01486-5
Lukassen S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, et al. SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020;39(10):1–15. https://doi.org/10.15252/embj.20105114
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–80. https://doi.org/10.1016/j.cell.2020.02.052
Aguiar JA, Tremblay BJ-M, Mansfield MJ, Woody O, Lobb B, Banerjee A, et al. Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue. Eur Respir J. 2020;56(3):2001123. https://doi.org/10.1183/13993003.01123-2020
Aoe T. Pathological Aspects of COVID-19 as a Conformational Disease and the Use of Pharmacological Chaperones as a Potential Therapeutic Strategy. Front Pharmacol. 2020;11:1095. https://doi.org/10.3389/fphar.2020.01095
Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell’s response to stress. Life Sci. 2019;226:156–63. https://doi.org/10.1016/j.lfs.2019.04.022
Gelman R, Bayatra A, Kessler A, Schwartz A, Ilan Y. Targeting SARS-CoV-2 receptors as a means for reducing infectivity and improving antiviral and immune response: an algorithm-based method for overcoming resistance to antiviral agents. Emerg Microbes Infect. 2020;9(1):1397–406. https://doi.org/10.1080/22221751.2020.1776161
Loeffelholz MJ, Tang Y-W. Laboratory diagnosis of emerging human coronavirus infections – the state of the art. Emerg Microbes Infect. 2020;9(1):747–56. https://doi.org/10.1080/22221751.2020.1745095
Jia HP, Look DC, Shi L, Hickey M, Pewe L, Netland J, et al. ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Differentiation of Human Airway Epithelia. J Virol. 2005;79(23):14614–21. https://doi.org/10.1128/JVI.79.23.14614-14621.2005
Shi-Chen Ou D, Lee S-B, Chu C-S, Chang L-H, Chung B, Juan L-J. Transcriptional activation of endoplasmic reticulum chaperone GRP78 by HCMV IE1-72 protein. Cell Res. 2011;21(4):642–53. https://doi.org/10.1038/cr.2011.10
Gutiérrez-Chamorro L, Riveira-Muñoz E, Barrios C, Palau V, Massanella M, Garcia-Vidal E, et al. SARS-CoV-2 infection suppresses ACE2 function and antiviral immune response in the upper respiratory tract of infected patients [Internet]. Immunology; 2020 Nov [cited 2022 Jan 11]. Available from: http://biorxiv.org/lookup/doi/10.1101/2020.11.18.388850
Zhuang MW, Cheng Y, Zhang J, Jiang X-M, Wang L, Deng J, et al. Increasing host cellular receptor—angiotensin‐converting enzyme 2 expression by coronavirus may facilitate 2019-nCoV (or SARS-CoV-2) infection. J Med Virol. 2020(92):2693–701. https://doi.org/10.1002/jmv.26139
Lodhi N, Singh R, Rajput SP, Saquib Q. SARS-CoV-2: Understanding the Transcriptional Regulation of ACE2 and TMPRSS2 and the Role of Single Nucleotide Polymorphism (SNP) at Codon 72 of p53 in the Innate Immune Response against Virus Infection. Int J Mol Sci. 2021 Aug 12;22(16):1–28. https://doi.org/10.3390/ijms22168660
Ha DP, Van Krieken R, Carlos AJ, Lee AS. The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection. J Infect. 2020;81(3):452–82. https://doi.org/10.1016/j.jinf.2020.06.017
Carlos AJ, Ha DP, Yeh D-W, Van Krieken R, Tseng C-C, Zhang P, et al. The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2, and GRP78 depleting antibody blocks viral entry and infection. J Biol Chem. 2021;296:100759. https://doi.org/10.1016/j.jbc.2021.100759
Ma’unah S, Mariani S, Sugiman. Estimasi Skewness (Kemiringan) dengan Menggunakan Metode Bootstrap dan Metode Jackknife. UNNES J Math. 2017;6(2):10. https://doi.org/10.15294/ujm.v6i2.11828
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