Interferon system for COVID-19

Abstract

SARS-CoV-2 is the causative agent of COVID-19 and infects the respiratory tract, blood cells, gastrointestinal tract, kidneys, liver, heart, brain and other organs. The ability of SARS-CoV-2 to escape from immune surveillance leads to deregulation of the immune response, cytokine storm and extensive tissue damage to infected organs. It is assumed that the pathogenesis of the deterioration of the course of COVID-19 is much more complicated and one of the mechanisms for the escape of SARS-Cov-2 from the influence of innate immunity is the inhibition of signaling pathways for the production and action of interferon (IFN). This review summarizes the role of the IFN system in SARS-CoV-2 infection and discusses the sophisticated mechanisms that coronaviruses have developed over the course of evolution to evade immune surveillance and suppress IFN responses. The IFN-related issues of counteraction to SARS-Cov-2 infection and the IFN-dependent adverse course of COVID-19 is also discussed.

Keywords:SARS-CoV-2; COVID-19; interferons; signaling pathways; interferon-stimulated genes

For citation. Narovlyansky A.N., Ershov F.I., Sanin A.V., Pronin A.V. Interferon system for COVID-19. Immuno- logiya. 2022; 43 (3): 245–54. DOI: https://doi.org/10.33029/0206-4952-2022-43-3-245-254 (in Russian)

Funding. The work was carried out within the state assignment of Ministry of Health of the Russian Federation (theme No. 056-00119-21-00).

Conflict of interests. The authors declare no conflict of interests.

Authors’ contributions. Authors made an equal contribution to the writing the article.

References

1. WHO Coronavirus (COVID-19) Dashboard. URL: https:covid19.who.int

2. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. Nat. Microbiol. 2020; 5: 536–44. DOI: https://doi.org/10.1038/s41564-020-0695-z

3. Xu Z., Shi L., Wang Y., Zhang J., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020; 8: 420–2. DOI: https://doi.org/10.1016/S2213-2600(20)30076-X

4. Nile S.H., Nile A., Qiu J., Li L., Jia X., Kai G. COVID-19: pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020; 53: 66–70. DOI: https://doi.org/10.1016/j.cytogfr.2020.05.002

5. Blanco-Melo D., Nilsson-Payant B.E., Liu W.C., Uhl S., et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020; 181 (5): 1036–45.e9. DOI: https://doi.org/10.1016/j.cell.2020.04.026

6. Zhou Z., Ren L., Zhang L., Zhong J., et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020; 27 (6): 883–90.e2. DOI: https://doi.org/10.1016/j.chom.2020.04.017

7. Gao Y., Wang C., Kang K., Peng Y., et al. Cytokine storm may not be the chief culprit for the deterioration of COVID-19. Viral Immunol. 2021; 34 (5): 336–41. DOI: http://doi.org/10.1089/vim.2020.0243

8. King C., Sprent J. Dual nature of type I interferons in SARS-CoV-2-induced inflammation. Trends Immunol. 2021; 42 (4): 312–22. DOI: https://doi.org/10.1016/j.it.2021.02.003

9. Schreiber G. The role of type I interferons in the pathogenesis and treatment of COVID-19. Front. Immunol. 2020; 11: 595739. DOI: https://doi.org/10.3389/fimmu.2020.595739

10. Ershov F.I., Narovlyansky A.N. Interferons and interferon inducers. Chapter 6. P. 123–147. In: Khaitov R.M., Ataullakhanov R.I., Shulzhenko A.E. (eds). Immunotherapy: a guide for doctors. 2nd ed. revised and additional. Moscow: GEOTAR-Media, 2018: 768 p. ISBN: 978-5-9704-4378-1. (in Russian)

11. Zhang X., Brann T.W., Zhou M., Yang J., et al. Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN. J. Immunol. 2011; 186 (8): 4541–5. DOI: https://doi.org/10.4049/jimmunol.1003389

12. McBride K.M., Banninger G., McDonald C., Reich N.C. Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-alpha. EMBO J. 2002; 21 (7): 1754–63. DOI: https://doi.org/10.1093/emboj/21.7.1754

13. Ershov F.I. Antiviral drugs. 2nd ed. Moscow: GEOTAR-Media, 2006: 312 p. ISBN: 5-9704-0164-1. (in Russian)

14. Ershov F.I., Kiselev O.I. Interferons and their inducers (from molecules to drugs). Moscow: GEOTAR-Media, 2005: 356 p. ISBN: 5-9704-0060-2. (in Russian)

15. Narovlyansky A.N. Classification and mechanisms of interferon action. In: F.I. Ershov (ed.). Interferon is 50 years old. Anniversary collection. Moscow, 2007: 44–50. ISBN: 978-5-903557-04-2. (in Russian)

16. Interferon-2011. Collection of scientific articles. In: F.I. Ershov, A.N. Narovlyansky (eds). Moscow, 2012: 512 p. ISBN: 978-5-9902840-2-9. (in Russian)

17. Мarsili G., Perrotti E., Remoli A.L., Acchioni C., et al. IFN regulatory factors and antiviral innate immunity: how viruses can get better. J. Interferon Cytokine Res. 2016; 36 (7): 414–32. DOI: https://doi.org/10.1089/jir.2016.0002

18. González-Navajas J.M., Li J., David M., Raz E. Immunomodulatory functions of type I interferons. Nat. Rev. Immunol. 2012; 12 (2): 125–35. DOI: https://doi.org/10.1038/nri3133

19. Kikkert M. Innate immune evasion by human respiratory RNA viruses. J. Innate Immun. 2020; 12 (1): 4–20. DOI: https://doi.org/10.1159/000503030

20. Kopecky-Bromberg S., Martinez-Sobrido L., Frieman M., Baric R., Palese P. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J. Virol. 2007; 81 (2): 548–57. DOI: https://doi.org/10.1128/JVI.01782-06

21. Kumar S., Nyodu R., Maurya V.K., Saxena S.K. Host immune response and immunobiology of human SARS-CoV-2 infection. In: Coronavirus Disease 2019 (COVID-19), Medical Virology: from Pathogenesis to Disease Control. Saxena S.K. (ed.). Singapore : Springer Nature, 2020: 43–53. DOI: https://doi.org/10.1007/978-981-15-4814-7_5

22. Felsenstein S., Herbert J.A., McNamara P.S., Hedrich C.M. COVID-19: immunology and treatment options. Clin. Immunol. 2020; 215: 108448. DOI: https://doi.org/10.1016/j.clim.2020.108448

23. Bahari Z., Jangravi Z., Ghoshooni H., et al. Pharmacological mechanism of immunomodulatory agents for the treatment of severe cases of COVID-19 infection. Inflamm. Res. 2021; 70: 389–405. DOI: https://doi.org/10.1007/s00011-021-01445-2

24. Channappanavar R., Fehr A.R., Vijay R., Mack M., et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016; 19 (2): 181–93. DOI: https://doi.org/10.1016/j.chom.2016.01.007 PMID: 26867177; PMCID: PMC4752723.

25. Catanzaro M., Fagiani F., Racchi M., Corsini E., et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduct. Target. Ther. 2020; 5 (1): 84. DOI: https://doi.org/10.1038/s41392-020-0191-1 PMID: 32467561; PMCID: PMC7255975.

26. Xia H., Shi P.-Y. Antagonism of type I interferon by severe acute respiratory syndrome coronavirus 2. J. Interferon Cytokine Res. 2020; 40 (12): 543–8. DOI: https://doi.org/10.1089/jir.2020.0214

27. Lee J.G., Huang W., Lee H., et al. Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor. Cell Biosci. 2021; 11: 58. DOI: https://doi.org/10.1186/s13578-021-00568-7

28. Dhakal S., Macreadie I. Genes of SARS-CoV-2 and emerging variants. Microbiol. Aust. 2021; 42 (1): 10–2. DOI: https://doi.org/10.1071/MA21004

29. Xia H., Cao Z., Xie X., Zhang X., et al. Evasion of type-I interferon by SARS-CoV-2. Cell Rep. 2020; 33 (1): 108234. DOI: https://doi.org/10.1016/j.celrep.2020.108234

30. Lei X., Dong X., Ma R., Wang W., et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 2020; 11: 3810. DOI: https://doi.org/10.1038/s41467-020-17665-9

31. Rabouw H.H., Langereis M.A., Knaap R.C.M., Dalebout T.J., et al. Middle East respiratory coronavirus accessory protein 4a inhibits PKR-mediated antiviral stress responses. PLoS Pathog. 2016; 12 (10): e1005982. DOI: https://doi.org/10.1371/journal.ppat.1005982

32. Jiang H.W., Zhang H.N., Meng Q.F., Xie J., et al. SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70. Cell. Mol. Immunol. 2020; 17 (9): 998–1000. DOI: https://doi.org/10.1038/s41423-020-0514-8

33. Israelow B., Song E., Mao T., Lu P., et al. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. J. Exp. Med. 2020; 217 (12): e20201241. DOI: https://doi.org/10.1084/jem.20201241

34. García-Sastre A. Ten strategies of interferon evasion by viruses. Cell Host Microbe. 2017; 22 (2): 176–84. DOI: https://doi.org/10.1016/j.chom.2017.07.012 PMID: 28799903; PMCID: PMC5576560.

35. Stertz S., Reichelt M., Spiegel M., Kuri T., et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology. 2007; 361 (2): 304–15. DOI: https://doi.org/10.1016/j.virol.2006.11.027 Epub 2007 Jan 8. PMID: 17210170; PMCID: PMC7103305.

36. Daffis S., Szretter K.J., Schriewer J., Li J., et al. 2’-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature. 2010; 468 (7322): 452–56. DOI: https://doi.org/10.1038/nature09489 PMID: 21085181; PMCID: PMC3058805.

37. Mantlo E., Bukreyeva N., Maruyama J., Paessler S., Huang C. Antiviral activities of type I interferons to SARS-CoV-2 infection. Antiviral Res. 2020; 179: 104811. DOI: https://doi.org/10.1016/j.antiviral.2020.104811 Epub 2020 Apr 29. PMID: 32360182; PMCID: PMC7188648.

38. Schroeder S., Pott F., Niemeyer D., Veith T., et al. Interferon antagonism by SARS-CoV-2: a functional study using reverse genetics. Lancet Microbe. 2021; 2 (5): e210–8. DOI: https://doi.org/10.1016/S2666-5247(21)00027-6 URL: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(21)00027-6/fulltext

39. Suryawanshi R.K., Koganti R., Agelidis A., Patil C.D., Shukla D. Dysregulation of cell signaling by SARS-CoV-2. Trends Microbiol. 2021; 29 (3): 224–37. DOI: https://doi.org/10.1016/j.tim.2020.12.007

40. Rodriguez-Morales A.J., Cardona-Ospina J.A., Gutierrez-Ocampo E., Villamizar-Pena R., et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med. Infect. Dis. 2020; 34: 101623. DOI: https://doi.org/10.1016/j.tmaid.2020.101623

41. Wei L.L., Wang W.J., Chen D.X., Xu B. Dysregulation of the immune response affects the outcome of critical COVID-19 patients. J. Med. Virol. 2020; 92 (11): 2768–76. DOI: https://doi.org/10.1002/jmv.26181 PMID: 32543740; PMCID: PMC7323247.

42. Daamen A.R., Bachali P., Owen K.A., Kingsmore K.M., et al. Comprehensive transcriptomic analysis of COVID-19 blood, lung, and airway. Sci. Rep. 2021; 11 (1): 7052. DOI: https://doi.org/10.1038/s41598-021-86002-x PMID: 33782412; PMCID: PMC8007747.

43. Martin-Sancho L., Lewinski M.K., Pache L. Functional landscape of SARS-CoV-2 cellular restriction. Mol. Cells. 2021; 81 (12): 2656–68.E8. DOI: https://doi.org/10.1016/j.molcel.2021.04.008

44. Faure E., Poissy J., Goffard A., Fournier C., et al. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside? PLoS One. 2014; 9 (2): e88716. DOI: https://doi.org/10.1371/journal.pone.0088716 PMID: 24551142; PMCID: PMC3925152.

45. Channappanavar R., Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol. 2017; 39 (5): 529–39. DOI: https://doi.org/10.1007/s00281-017-0629-x

46. Huang K.J., Su I.J., Theron M., Wu Y.C., et al. An interferon-gamma-related cytokine storm in SARS patients. J. Med. Virol. 2005; 75 (2): 185–94. DOI: https://doi.org/10.1002/jmv.20255 PMID: 15602737; PMCID: PMC7166886.

47. Cameron M.J., Ran L., Xu L., Danesh A., et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J. Virol. 2007; 81 (16): 8692–706. DOI: https://doi.org/10.1128/JVI.00527-07 PMID: 17537853; PMCID: PMC1951379.

48. Hadjadj J., Yatim N., Barnabei L., Corneau A., et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020; 369: 718–24. DOI: https://doi.org/10.1126/science.abc6027

49. Mosser D.M., Hamidzadeh K., Goncalves R. Macrophages and the maintenance of homeostasis. Cell. Mol. Immunol. 2021; 18: 579–87. DOI: https://doi.org/10.1038/s41423-020-00541-3

50. Diao B., Wang C., Tan Y., Chen X., et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). Front. Immunol. 2020; 11: 827. DOI: https://doi.org/10.3389/fimmu.2020.00827

51. Zhang Q., Bastard P., Liu Z., Le Pen J., et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020; 370 (6515): eabd4570. DOI: https://doi.org/10.1126/science.abd4570 PMID: 32972995; PMCID: PMC7857407.

52. Bastard P., Rosen L.B., Zhang Q., Michailidis E., et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020; 370 (6515): eabd4585. DOI: https://doi.org/10.1126/science.abd4585 PMID: 32972996; PMCID: PMC7857397.

53. Lucas C., Wong P., Klein J., Castro T.B.R., et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature. 2020; 584 (7821): 463–9. DOI: https://doi.org/10.1038/s41586-020-2588-y PMID: 32717743; PMCID: PMC7477538.

54. Agrawal A. Mechanisms and implications of age-associated impaired innate interferon secretion by dendritic cells: a mini-review. Gerontology. 2013; 59 (5): 421–6. DOI: https://doi.org/10.1159/000350536 PMID: 23615484.

55. Sun S., Zhang X., Tough D.F., Sprent J. Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med. 1998; 188 (12): 2335–42. DOI: https://doi.org/10.1084/jem.188.12.2335 PMID: 9858519; PMCID: PMC2212431.

56. Moore J.B., June C.H. Cytokine release syndrome in severe COVID-19. Science. 2020; 368 (6490): 473–4. DOI: https://doi.org/10.1126/science.abb8925 PMID: 32303591.

57. Li S., Zhang Y., Guan Z., Li H., et al. SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation. Signal Transduct. Target. Ther. 2020; 5 (1): 235. DOI: https://doi.org/10.1038/s41392-020-00334-0 PMID: 33037188; PMCID: PMC7545816.

58. Yang M. Cell pyroptosis, a potential pathogenic mechanism of 2019-nCoV infection. SSRN. 2020. DOI: https://doi.org/10.2139/ssrn.3527420 URL: https://ssrn.com/abstract=3527420

59. Velazquez-Salinas L., Verdugo-Rodriguez A., Rodriguez L.L., Borca M.V. The role of interleukin 6 during viral infections. Front. Microbiol. 2019; 10: 1057. DOI: https://doi.org/10.3389/fmicb.2019.01057 PMID: 31134045; PMCID: PMC6524401.

60. Cho J.H., Kim H.O., Webster K., Palendira M., et al. Calcineurin-dependent negative regulation of CD94/NKG2A expression on naive CD8+ T cells. Blood. 2011; 118 (1): 116–28. DOI: https://doi.org/10.1182/blood-2010-11-317396 PMID: 21540458.

61. Wu S.C., Arthur C.M., Wang J., Verkerke H., et al. The SARS-CoV-2 receptor-binding domain preferentially recognizes blood group A. Blood Adv. 2021; 5 (5): 1305–9. DOI: https://doi.org/10.1182/bloodadvances.2020003259 PMID: 33656534; PMCID: PMC7929867.

62. Wu B.B., Gu D.Z., Yu J.N., Yang J., Shen W.Q. Association between ABO blood groups and COVID-19 infection, severity and demise: a systematic review and meta-analysis. Infect. Genet. Evol. 2020; 84: 104485. DOI: https://doi.org/10.1016/j.meegid.2020.104485 PMID: 32739464; PMCID: PMC7391292.

63. Ershov F.I., Gotovtseva E.L., Nosik N.N. Interferon status is normal. Immunologiya. 1986; 3: 52–4. (in Russian)

64. About adaptation of the causative agent of COVID-19 to the human population. Federal’naya sluzhba po nadzoru v sfere zashchity prav potrebiteley i blagopoluchiya cheloveka, 2021. URL: https://www.rospotrebnadzor.ru/about/info/predpr/news_predpr.php?ELEMENT_ID=15426 (in Russian)

EDITOR-IN-CHIEF
EDITOR-IN-CHIEF
Musa R. Khaitov

Corresponding member of Russian Academy of Sciences, MD, Professor, Director of the NRC Institute of Immunology FMBA of Russia

Вскрытие
Medicine today

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