Innate Immunity and Interferon in SARS-CoV-2 Infection Outcome

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2023 Jul 12

PMID 37437537

Authors

Ram Savan

Michael Gale Jr

Affiliations

Soon will be listed here.

Abstract

Innate immunity and the actions of type I and III interferons (IFNs) are essential for protection from SARS-CoV-2 and COVID-19. Each is induced in response to infection and serves to restrict viral replication and spread while directing the polarization and modulation of the adaptive immune response. Owing to the distribution of their specific receptors, type I and III IFNs, respectively, impart systemic and local actions. Therapeutic IFN has been administered to combat COVID-19 but with differential outcomes when given early or late in infection. In this perspective, we sort out the role of innate immunity and complex actions of IFNs in the context of SARS-CoV-2 infection and COVID-19. We conclude that IFNs are a beneficial component of innate immunity that has mediated natural clearance of infection in over 700 million people. Therapeutic induction of innate immunity and use of IFN should be featured in strategies to treat acute SARS-CoV-2 infection in people at risk for severe COVID-19.

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References

Chakrabarti A, Jha B, Silverman R . New insights into the role of RNase L in innate immunity. J Interferon Cytokine Res. 2010; 31(1):49-57. PMC: 3021357. DOI: 10.1089/jir.2010.0120. View

Anaeigoudari A, Mollaei H, Arababadi M, Nosratabadi R . Severe Acute Respiratory Syndrome Coronavirus 2: The Role of the Main Components of the Innate Immune System. Inflammation. 2021; 44(6):2151-2169. PMC: 8442517. DOI: 10.1007/s10753-021-01519-7. View

Bastard P, Vazquez S, Liu J, Laurie M, Wang C, Gervais A . Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs. Sci Immunol. 2022; 8(90):eabp8966. PMC: 9210448. DOI: 10.1126/sciimmunol.abp8966. View

Casazza R, Lazear H . Why Is IFN-λ Less Inflammatory? One IRF Decides. Immunity. 2019; 51(3):415-417. DOI: 10.1016/j.immuni.2019.08.019. View

Song J, Chow R, Pena-Hernandez M, Zhang L, Loeb S, So E . LRRC15 inhibits SARS-CoV-2 cellular entry in trans. PLoS Biol. 2022; 20(10):e3001805. PMC: 9595563. DOI: 10.1371/journal.pbio.3001805. View

Nice T, Baldridge M, McCune B, Norman J, Lazear H, Artyomov M . Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science. 2014; 347(6219):269-73. PMC: 4398891. DOI: 10.1126/science.1258100. View

Agyapon-Ntra K, McSharry P . A global analysis of the effectiveness of policy responses to COVID-19. Sci Rep. 2023; 13(1):5629. PMC: 10078072. DOI: 10.1038/s41598-023-31709-2. View

Ugalde A, Bretones G, Rodriguez D, Quesada V, Llorente F, Fernandez-Delgado R . Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells. EMBO J. 2022; 41(21):e110727. PMC: 9627672. DOI: 10.15252/embj.2022110727. View

Pfaender S, Mar K, Michailidis E, Kratzel A, Boys I, Vkovski P . LY6E impairs coronavirus fusion and confers immune control of viral disease. Nat Microbiol. 2020; 5(11):1330-1339. PMC: 7916999. DOI: 10.1038/s41564-020-0769-y. View

10.

Baldridge M, Lee S, Brown J, McAllister N, Urbanek K, Dermody T . Expression of on Intestinal Epithelial Cells Is Critical to the Antiviral Effects of Interferon Lambda against Norovirus and Reovirus. J Virol. 2017; 91(7). PMC: 5355594. DOI: 10.1128/JVI.02079-16. View

11.

Kratzel A, Kelly J, Vkovski P, Portmann J, Bruggemann Y, Todt D . A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets. PLoS Biol. 2021; 19(12):e3001490. PMC: 8741300. DOI: 10.1371/journal.pbio.3001490. View

12.

Leist S, Dinnon 3rd K, Schafer A, Tse L, Okuda K, Hou Y . A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice. Cell. 2020; 183(4):1070-1085.e12. PMC: 7510428. DOI: 10.1016/j.cell.2020.09.050. View

13.

Green R, Ireton R, Gale Jr M . Interferon-stimulated genes: new platforms and computational approaches. Mamm Genome. 2018; 29(7-8):593-602. DOI: 10.1007/s00335-018-9755-6. View

14.

Drappier M, Michiels T . Inhibition of the OAS/RNase L pathway by viruses. Curr Opin Virol. 2015; 15:19-26. PMC: 7185432. DOI: 10.1016/j.coviro.2015.07.002. View

15.

da Silva R, Goncalves J, Zanin R, Schuch F, Souza A . Circulating Type I Interferon Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis. Front Immunol. 2021; 12:657363. PMC: 8149905. DOI: 10.3389/fimmu.2021.657363. View

16.

Forero A, Ozarkar S, Li H, Lee C, Hemann E, Nadjsombati M . Differential Activation of the Transcription Factor IRF1 Underlies the Distinct Immune Responses Elicited by Type I and Type III Interferons. Immunity. 2019; 51(3):451-464.e6. PMC: 7447158. DOI: 10.1016/j.immuni.2019.07.007. View

17.

Wang R, Simoneau C, Kulsuptrakul J, Bouhaddou M, Travisano K, Hayashi J . Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses. Cell. 2020; 184(1):106-119.e14. PMC: 7723770. DOI: 10.1016/j.cell.2020.12.004. View

18.

Hoffmann H, Sanchez-Rivera F, Schneider W, Luna J, Soto-Feliciano Y, Ashbrook A . Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors. Cell Host Microbe. 2020; 29(2):267-280.e5. PMC: 7833927. DOI: 10.1016/j.chom.2020.12.009. View

19.

Morin B, Rabah N, Boretto-Soler J, Tolou H, Alvarez K, Canard B . High yield synthesis, purification and characterisation of the RNase L activators 5'-triphosphate 2'-5'-oligoadenylates. Antiviral Res. 2010; 87(3):345-52. DOI: 10.1016/j.antiviral.2010.06.003. View

20.

Zimmer M, Kibe A, Rand U, Pekarek L, Ye L, Buck S . The short isoform of the host antiviral protein ZAP acts as an inhibitor of SARS-CoV-2 programmed ribosomal frameshifting. Nat Commun. 2021; 12(1):7193. PMC: 8664833. DOI: 10.1038/s41467-021-27431-0. View