From Mild Cases to Critical Cases of COVID-19: The Role of Genes in Inflammasome and Mitochondrial Dynamics
-
Azam Kia
,
Vahideh Hajhasan
,
Mona Nadi
,
Azam Samei
,
Sadeq Azimzadeh Jamalkandi
,
Shahram Parvin
,
Ali Saffaie
,
Pedram Basirjafar
,
Jafar Salimian
,
Azam Samei
Abstract
The coronavirus disease 2019 (CVOID-19) has varied clinical manifestations including mild to severe acute respiratory symptoms. Inflammasome complex and mitochondria play an important role in initiating inflammatory responses and could potentially be affected by this infection. To study the inflammasome and mitochondrial fission and fusion gene expression levels in COVID-19 patients, we designed this experiment.
The inflammasome and mitochondrial gene expression profiles were determined by real-time polymerase chain reaction in the peripheral blood of 70 hospitalized CVOID-19 patients with mild to moderate symptoms (HOSP) and 30 ICU patients with severe symptoms (ICU) compared to 20 healthy controls (HC).
The results indicated that the expression of the dynamin-related protein-1 was extremely suppressed in HOSP while it came back to the normal range in the ICU group. However, the expression of fission 1 protein had a non-significant increase in HOSP and a decrease in the ICU group. The mitofusin-1 and dominant optic atrophy genes showed high expression levels (10-fold) and (70-fold), respectively, in the HOSP group. However, mitofusin-2 significantly decreased in both groups. Although leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) and apoptosis-associated speck-like protein containing a caspase activating and recruitment domain genes dramatically increased in both groups (10 and 4-fold), other inflammasome genes declined in both groups. Finally, Nuclear factor kappa-light-chain-enhancer of activate d B cells (NF-κB) extremely decreased, and Intreleukine-1 showed high expression in ICU patients (3-fold).
CVOID-19 infection suppresses the fission genes and elevates the fusion gene expression in mitochondria, and it can cause activation of the inflammasome via the NLRP3 pathway.
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28. Banoth B, Cassel SL. Mitochondria in innate immune signaling. J Transl Res. 2018;202(11):52-68.
29. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. SARS-CoV-2 accessory proteins in viral pathogenesis: knowns and unknowns. Front immunol. 2021;12:708264.
30. Shi C-S, Qi H-Y, Boularan C, Huang N-N, Abu-Asab M, Shelhamer JH, et al. SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J Immun. 2014;193(6):3080-9.
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33. Prasun P. COVID-19: a mitochondrial perspective. DNA and Cell Biology. 2021;40(6):713-9.
34. Junqueira C, Crespo Â, Ranjbar S, Lewandrowski M, Ingber J, de Lacerda LB, et al. SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release. Res Sq. 2021.
35. Kaivola J, Nyman TA, Matikainen S. Inflammasomes and SARS-CoV-2 infection. Viruses. 2021;13(12):2513.
36. Ferreira AC, Soares VC, de Azevedo-Quintanilha IG, Dias SdSG, Fintelman-Rodrigues N, Sacramento CQ, et al. SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes. Cell Death Discov. 2021;7(1):43.
37. Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct. Target Ther. 2017;2(1):1-9.
38. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506.
39. Pan P, Shen M, Yu Z, Ge W, Chen K, Tian M, et al. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun. 2021;12(1):4664.
40. Nagaraja S, Jain D, Kesavardhana S. Inflammasome regulation in driving COVID-19 severity in humans and immune tolerance in bats. J Leukoc Biol. 2022;111(2):497-508.
41. Mahroum N, Alghory A, Kiyak Z, Alwani A, Seida R, Alrais M, et al. Ferritin–from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun. 2022;126(14):102778.
42. Fratta Pasini AM, Stranieri C, Girelli D, Busti F, Cominacini L. Is ferroptosis a key component of the process leading to multiorgan damage in COVID-19? Antioxidants. 2021;10(11):1677.
43. Sfera A, Osorio C, Maguire G, Rahman L, Afzaal J, Cummings M, et al. COVID-19, ferrosenescence and neurodegeneration, a mini-review. Prog Neuro-Psychopharmacol Biol Psychiatry. 2021;109:110230.
2. Khandia R, Singhal S, Alqahtani T, Kamal MA, Nahed A, Nainu F, et al. Emergence of SARS-CoV-2 Omicron (B. 1.1. 529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ Res. 2022;209:112816.
3. Zoulikha M, Huang F, Wu Z, He W. COVID-19 inflammation and implications in drug delivery. J Control Release. 2022;346:260-74.
4. Wang Y, Wu M, Li Y, Yuen HH, He M-L. The effects of SARS-CoV-2 infection on modulating innate immunity and strategies of combating inflammatory response for COVID-19 therapy. J Biomed Sci. 2022;29(1):1-19.
5. Kaur I, Sharma A, Jakhar D, Das A, Aradhya SS, Sharma R, et al. Coronavirus disease (COVID‐19): An updated review based on current knowledge and existing literature for dermatologists. Dermatol Ther. 2020;33(4):e13677.
6. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.
7. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-9.
8. Lauro R, Irrera N, Eid AH, Bitto A. Could antigen presenting cells represent a protective element during SARS-CoV-2 infection in children? J pathog. 2021;10(4):476.
9. Chehardoli B, Nadi M, Abadi AK, Kia A, Shahriary A, Salimian J. Immunomodulatory Effect of Curcumin in the Upregulation of Inflammasome Pathway Genes Induced by Sulfur Mustard Analog: An In-vitro Study. Iran J Allergy Asthma Immunol. 2021;20(2):169-77.
10. Asnaf SE, Sabetghadam M, Jaafarinejad H, Halabian R, Parvin S, Vahedi E, et al. Is the Inflammasome Pathway Active in the Peripheral Blood of Sulfur Mustard-exposed Patients? IJAAI. 2019.
11. Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol. 2021;21(11):694-703.
12. Zheng D, Liwinski T, Elinav E. Inflammasome activation and regulation: toward a better understanding of complex mechanisms. Cell Discov. 2020;6(1):36.
13. Sharma M, de Alba E. Structure, activation and regulation of NLRP3 and AIM2 inflammasomes. Int J Mol Sci. 2021;22(2):872.
14. Freeman TL, Swartz TH. Targeting the NLRP3 inflammasome in severe COVID-19. Front immunol. 2020;1518.
15. Zhao N, Di B, Xu L-l. The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies. Cytokine Growth Factor rev. 2021;61(5):2-15.
16. Biacchesi S, LeBerre M, Lamoureux A, Louise Y, Lauret E, Boudinot P, et al. Mitochondrial antiviral signaling protein plays a major role in induction of the fish innate immune response against RNA and DNA viruses. Virol J. 2009;83(16):7815-27.
17. Koshiba T. Mitochondrial-mediated antiviral immunity. Biochim Biophys Acta Mol Cell Res. 2013;1833(1):225-32.
18. Sorouri M, Chang T, Hancks DC. Mitochondria and viral infection: advances and emerging battlefronts. MBio. 2022;13(1):e02096-21.
19. Kia A, Nadi M, Hajhasan V, Salimian J. Alterations in Mitochondrial and Inflammasome Homeostasis by 2-Chloroethyl Ethyl Sulfide and Their Mitigation by Curcumin: An in Vitro Study. Iran J Allergy Asthma Immunol. 2021;20(5):614-22.
20. Saleh J, Peyssonnaux C, Singh KK, Edeas M. Mitochondria and microbiota dysfunction in COVID-19 pathogenesis. Mitochondrion. 2020;54(3):1-7.
21. Wu KE, Fazal FM, Parker KR, Zou J, Chang HY. RNA-GPS predicts SARS-CoV-2 RNA residency to host mitochondria and nucleolus. Cell syst. 2020;11(1):102-8. e3.
22. Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265-9.
23. Guzzi PH, Mercatelli D, Ceraolo C, Giorgi FM. Master regulator analysis of the SARS-CoV-2/human interactome. J Clin Med. 2020;9(4):982.
24. Zhang Z-W, Xu X-C, Liu T, Yuan S. Mitochondrion-permeable antioxidants to treat ROS-burst-mediated acute diseases. Oxidative Med Cell Longev. 2016;2016.
25. Burtscher J, Cappellano G, Omori A, Koshiba T, Millet GP. Mitochondria: in the cross fire of SARS-CoV-2 and immunity. IScience. 2020;23(10).
26. Guarnieri JW, Angelin A, Murdock DG, Schaefer P, Portluri P, Lie T, et al. SARS-COV-2 viroporins activate the NLRP3-inflammasome by the mitochondrial permeability transition pore. Front immunol. 2023;14(2):1064293.
27. Shoraka S, Samarasinghe AE, Ghaemi A, Mohebbi SR. Host mitochondria: more than an organelle in SARS-CoV-2 infection. Front. cell infect microbiol. 2023;13:1225487.
28. Banoth B, Cassel SL. Mitochondria in innate immune signaling. J Transl Res. 2018;202(11):52-68.
29. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. SARS-CoV-2 accessory proteins in viral pathogenesis: knowns and unknowns. Front immunol. 2021;12:708264.
30. Shi C-S, Qi H-Y, Boularan C, Huang N-N, Abu-Asab M, Shelhamer JH, et al. SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J Immun. 2014;193(6):3080-9.
31. Singh K, Chen Y-C, Hassanzadeh S, Han K, Judy JT, Seifuddin F, et al. Network analysis and transcriptome profiling identify autophagic and mitochondrial dysfunctions in SARS-CoV-2 infection. Front genet. 2021;12:599261.
32. Holder K, Reddy PH. The COVID-19 effect on the immune system and mitochondrial dynamics in diabetes, obesity, and dementia. Neuroscientist. 2021;27(4):331-9.
33. Prasun P. COVID-19: a mitochondrial perspective. DNA and Cell Biology. 2021;40(6):713-9.
34. Junqueira C, Crespo Â, Ranjbar S, Lewandrowski M, Ingber J, de Lacerda LB, et al. SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release. Res Sq. 2021.
35. Kaivola J, Nyman TA, Matikainen S. Inflammasomes and SARS-CoV-2 infection. Viruses. 2021;13(12):2513.
36. Ferreira AC, Soares VC, de Azevedo-Quintanilha IG, Dias SdSG, Fintelman-Rodrigues N, Sacramento CQ, et al. SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes. Cell Death Discov. 2021;7(1):43.
37. Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct. Target Ther. 2017;2(1):1-9.
38. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020;395(10223):497-506.
39. Pan P, Shen M, Yu Z, Ge W, Chen K, Tian M, et al. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun. 2021;12(1):4664.
40. Nagaraja S, Jain D, Kesavardhana S. Inflammasome regulation in driving COVID-19 severity in humans and immune tolerance in bats. J Leukoc Biol. 2022;111(2):497-508.
41. Mahroum N, Alghory A, Kiyak Z, Alwani A, Seida R, Alrais M, et al. Ferritin–from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun. 2022;126(14):102778.
42. Fratta Pasini AM, Stranieri C, Girelli D, Busti F, Cominacini L. Is ferroptosis a key component of the process leading to multiorgan damage in COVID-19? Antioxidants. 2021;10(11):1677.
43. Sfera A, Osorio C, Maguire G, Rahman L, Afzaal J, Cummings M, et al. COVID-19, ferrosenescence and neurodegeneration, a mini-review. Prog Neuro-Psychopharmacol Biol Psychiatry. 2021;109:110230.
| Files | ||
| Issue | Vol 23 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i4.16213 | |
| Keywords | ||
| Corona disease 2019 (COVID-19) Inflammasome Mitochondria | ||
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How to Cite
1.
Kia A, Hajhasan V, Nadi M, Samei A, Azimzadeh Jamalkandi S, Parvin S, Saffaie A, Basirjafar P, Salimian J, Samei A. From Mild Cases to Critical Cases of COVID-19: The Role of Genes in Inflammasome and Mitochondrial Dynamics. Iran J Allergy Asthma Immunol. 2024;23(4):393-402.
