Evaluation of two types of IFN-1 induced gene expression (ly6e and usp18) and its association with the severity of clinical symptoms in COVID-19 patients

Document Type : Original Article

Authors

1 Department of immunology, Faculty of Medicine, Shahed University, Tehran, Iran

2 Immunoregulation Research Center, Shahed University, Tehran, Iran

3 Non-communicable Diseases Research Center, Fasa University of Medical Science, Fasa, Iran

Abstract

Background and Objective: Covid-19 disease as a pandemic with high spreading power and a wide range of clinical symptoms and lack of definitive treatment is a challenge for mankind in recent years. The antiviral response of type 1 interferon against the SARS-COV-2 virus is one of the most important pathways of the innate immune system in dealing with this disease. The purpose of this study was to investigate the relationship between the expression of two genes, ly6e and usp18, with the severity of clinical symptoms in patients with covid-19.
Materials and Methods: Peripheral blood samples were prepared from patients and their DNA was extracted, then the expression of ly6e and usp18 genes was measured by real-time PCR method. cDNA samples were first amplified using specific primers. Data analysis was performed using chi-square, Kruskal-Wallis and Mann-Whitney tests. A significance level of 0.05 was considered.
Results: The expression of the ly6e gene was significantly (p=0.008) decreased in the hospitalized group compared to the control group. No significant difference was seen in the expression of the usp18 gene among the studied groups.
Conclusion: Proper expression of ly6e protein can be related to controlling the severity of clinical symptoms of covid-19 disease.
 

Keywords


  1. Worobey M, Levy JI, Malpica Serrano L, Crits-Christoph A, Pekar JE, Goldstein SA, et al. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science 2022;377(6609):951-9.
  2. Struyf T, Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Leeflang MM, et al. Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID‐ Cochrane Database of Systematic Reviews 2022(5).
  3. Van Kessel SA, Olde Hartman TC, Lucassen PL, van Jaarsveld CH. Post-acute and long-COVID-19 symptoms in patients with mild diseases: a systematic review. Family Practice 2022;39(1):159-67.
  4. Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, et al. Persistent COVID-19 symptoms in a community study of 606,434 people in England. Nature Communications 2022;13(1):1-10.
  5. Kim AW, Nyengerai T, Mendenhall E. Evaluating the mental health impacts of the COVID-19 pandemic: Perceived risk of COVID-19 infection and childhood trauma predict adult depressive symptoms in urban South Africa. Psychological Medicine 2022;52(8):1587-99.
  6. Paul AK, Hossain MK, Mahboob T, Nissapatorn V, Wilairatana P, Jahan R, et al. Does oxidative stress management help alleviation of COVID-19 symptoms in patients experiencing diabetes? Nutrients 2022;14(2):321.
  7. Galbraith MD, Kinning KT, Sullivan KD, Araya P, Smith KP, Granrath RE, et al. Specialized interferon action in COVID-19. Proceedings of the National Academy of Sciences 2022;119(11):e2116730119.
  8. Nagaoka K, Kawasuji H, Murai Y, Kaneda M, Ueno A, Miyajima Y, et al. Circulating Type I Interferon Levels in the Early Phase of COVID-19 Are Associated With the Development of Respiratory Failure. Frontiers in Immunology 2022;13.
  9. Sodeifian F, Nikfarjam M, Kian N, Mohamed K, Rezaei N. The role of type I interferon in the treatment of COVID‐ Journal of Medical Virology 2022;94(1):63-81.
  10. Soltani-Zangbar MS, Parhizkar F, Ghaedi E, Tarbiat A, Motavalli R, Alizadegan A, et al. A comprehensive evaluation of the immune system response and type-I Interferon signaling pathway in hospitalized COVID-19 patients. Cell Communication and Signaling 2022;20(1):1-15.
  11. Aquino A, Paschoalin VMF, Tessaro LLG, Raymundo-Pereira PA, Conte-Junior CA. Updating the use of nano-biosensors as promising devices for the diagnosis of coronavirus family members: A systematic review. Journal of Pharmaceutical and Biomedical Analysis 2022:114608.
  12. Bajkó N, Fülöp Z, Pércsi KN. Changes in the innovation-and marketing-habits of family SMEs in the foodstuffs industry, caused by the coronavirus pandemic in Hungary. Sustainability 2022;14(5):2914.
  13. Castro VM, Rosand J, Giacino JT, McCoy TH, Perlis RH. Case-control study of neuropsychiatric symptoms in electronic health records following COVID-19 hospitalization in 2 academic health systems. Molecular Psychiatry 2022:1-6.
  14. Thye AY-K, Law JW-F, Tan LT-H, Pusparajah P, Ser H-L, Thurairajasingam S, et al. Psychological symptoms in COVID-19 patients: insights into pathophysiology and risk factors of long COVID-19. Biology 2022;11(1):61.
  15. Sneller MC, Liang CJ, Marques AR, Chung JY, Shanbhag SM, Fontana JR, et al. A longitudinal study of COVID-19 sequelae and immunity: baseline findings. Annals of Internal Medicine 2022 ;175(7):969-979. doi: 10.7326/M21-4905.
  16. Frasca F, Scordio M, Santinelli L, Gabriele L, Gandini O, Criniti A, et al. Anti‐IFN‐α/‐ω neutralizing antibodies from COVID‐19 patients correlate with downregulation of IFN response and laboratory biomarkers of disease severity. European Journal of Immunology 2022;52(7):1120-1128. doi: 10.1002/eji.202249824.
  17. Khanmohammadi S, Rezaei N, Khazaei M, Shirkani A. A case of autosomal recessive interferon alpha/beta receptor alpha chain (IFNAR1) deficiency with severe COVID-19. Journal of Clinical Immunology 2022;42(1):19-24.
  18. Li T, Liu W, Wang C, Wang M, Hui W, Lu J, et al. Multidimension Analysis of the Prognostic Value, Immune Regulatory Function, and ceRNA Network of LY6E in Individuals with Colorectal Cancer. Journal of Immunolgy Research 2022.
  19. Zhang Q, Jia Y, Pan P, Zhang X, Jia Y, Zhu P, et al. α5-nAChR associated with Ly6E modulates cell migration via TGF-β1/Smad signaling in non-small cell lung cancer. Carcinogenesis 2022;43(4):393-404.
  20. Martin AM, Roach M, Jones LA, Thorpe D, Coleman RA, Allman C, et al. Single-cell gene expression links SARS-CoV-2 infection and gut serotonin. Gut 2022.
  21. Zhao X, Zheng S, Chen D, Zheng M, Li X, Li G, et al. LY6E restricts entry of human coronaviruses, including currently pandemic SARS-CoV-2. Journal of Virology 2020;94(18):e00562-20.
  22. Martin-Fernandez M, Buta S, Le Voyer T, Li Z, Dynesen LT, Vuillier F, et al. A partial form of inherited human USP18 deficiency underlies infection and inflammation. Journal of Experimental Medicine 2022;219(4):e20211273.
  23. Oki N, Yamada S, Tanaka T, Fukui H, Hatakeyama S, Okumura F. Curcumin partly prevents ISG15 activation via ubiquitin-activating enzyme E1-like protein and decreases ISGylation. Biochemical and Biophysical Research Communications 2022; 625:94-101.
  24. Vere G, Alam MR, Farrar S, Kealy R, Kessler BM, O’Brien DP, et al. Targeting the Ubiquitylation and ISGylation Machinery for the Treatment of COVID-19. Biomolecules 2022;12(2):300.
  25. Wang F, Yao Y, Wu Y, Lu Y. USP18 alleviates neurotoxicity induced by sevoflurane via AKT and NF-κB pathways. Molecular & Cellular Toxicology 2022:1-8.
  26. Mirzalieva O, Juncker M, Schwartzenburg J, Desai S. ISG15 and ISGylation in Human Diseases. Cells 2022;11(3):538.
  27. Tang J, Tang A, Jia N, Du H, Liu C, Zhu J, et al. Free ISG15 Inhibits the Replication of Peste des Petits Ruminants Virus by Breaking the Interaction of Nucleoprotein and Phosphoprotein. Microbiology Spectrum 2022:e01031-22.
  28. Wang T, Li C, Wang M, Zhang J, Zheng Q, Liang L, et al. Expedient Synthesis of Ubiquitin‐like Protein ISG15 Tools Through Chemo‐Enzymatic Ligation Catalyzed by a Viral Protease Lbpro. Angewandte Chemie 2022 ;61(40):e202206205. doi: 10.1002/anie.202206205.
  29. Waqas SFuH, Sohail A, Nguyen AHH, Usman A, Ludwig T, Wegner A, et al. ISG15 deficiency features a complex cellular phenotype that responds to treatment with itaconate and derivatives. Clinical and Translational Medicine 2022;12(7):e931.
  30. Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, evaluation, and treatment of coronavirus (COVID-19). Statpearls [internet] 2022; PMID: 32150360.
  31. Chandel V, Sharma PP, Raj S, Choudhari R, Rathi B, Kumar D. Structure-based drug repurposing for targeting Nsp9 replicase and spike proteins of severe acute respiratory syndrome coronavirus 2. Journal of Biomolecular Structure and Dynamics 2022;40(1):249-62.
  32. Hui DS, Zumla A. Advances in the epidemiology, clinical features, diagnosis, clinical management and prevention of coronavirus disease 2019. Current Opinion in Pulmonary Medicine 2022;28(3):166-73.
  33. Wang W, Peng X, Jin Y, Pan JA, Guo D. Reverse genetics systems for SARS‐CoV‐ Journal of Medical Virology 2022 ;94(7):3017-3031. doi: 10.1002/jmv.27738.
  34. Zhou P, Yuan M, Song G, Beutler N, Shaabani N, Huang D, et al. A human antibody reveals a conserved site on beta-coronavirus spike proteins and confers protection against SARS-CoV-2 infection. Science Translational Medicine 2022;14(637):eabi9215.
  35. Zhai S-L, Sun M-F, Zhang J-F, Zheng C, Liao M. Spillover infection of common animal coronaviruses to humans. The Lancet Microbe 2022;3(11):e808. doi: 10.1016/S2666-5247(22)00198-7.
  36. Wagh PW, Raut R, Kumbhalkar S, Kanojiya DR. Structure Of Coronavirus. ECS Transactions 2022;107(1):17297.
  37. Forni D, Cagliani R, Pontremoli C, Clerici M, Sironi M. The substitution spectra of coronavirus genomes. Briefings in Bioinformatics 2022;23(1):bbab382.
  38. Sathipati SY, Shukla SK, Ho S-Y. Tracking the amino acid changes of spike proteins across diverse host species of severe acute respiratory syndrome coronavirus 2. Iscience 2022;25(1):103560.
  39. Guo Z, Zhang C, Zhang C, Cui H, Chen Z, Jiang X, et al. SARS-CoV-2-related pangolin coronavirus exhibits similar infection characteristics to SARS-CoV-2 and direct contact transmissibility in hamsters. Iscience 2022;25(6):104350.
  40. Rouaud F, Méan I, Citi S. The ACE2 Receptor for Coronavirus Entry Is Localized at Apical Cell—Cell Junctions of Epithelial Cells. Cells 2022;11(4):627.
  41. Villafañe L, Vaulet LG, Viere FM, Klepp LI, Forrellad MA, Bigi MM, et al. Development and evaluation of a low cost IgG ELISA test based in RBD protein for COVID-19. Journal of Immunological Methods 2022;500:113182.
  42. Yang Q-Y, Yang Y-L, Tang Y-X, Qin P, Wang G, Xie J-Y, et al. Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids. PLoS Pathogens 2022;18(6):e1010620.
  43. Zhao X, Zheng S, Chen D, Zheng M, Li X, Li G, et al. LY6E restricts entry of human coronaviruses, including currently pandemic SARS-CoV-2. Journal of Virology 2020;94(18):e00562-20.