Interferon-stimulated Genes and Their Antiviral Activity Against SARS-CoV-2

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2024 Aug 22

PMID 39171921

Authors

Ana Maria Ortega-Prieto

Jose M Jimenez-Guardeno

Affiliations

Soon will be listed here.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic remains an international health problem caused by the recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of May 2024, SARS-CoV-2 has caused more than 775 million cases and over 7 million deaths globally. Despite current vaccination programs, infections are still rapidly increasing, mainly due to the appearance and spread of new variants, variations in immunization rates, and limitations of current vaccines in preventing transmission. This underscores the need for pan-variant antivirals and treatments. The interferon (IFN) system is a critical element of the innate immune response and serves as a frontline defense against viruses. It induces a generalized antiviral state by transiently upregulating hundreds of IFN-stimulated genes (ISGs). To gain a deeper comprehension of the innate immune response to SARS-CoV-2, its connection to COVID-19 pathogenesis, and the potential therapeutic implications, this review provides a detailed overview of fundamental aspects of the diverse ISGs identified for their antiviral properties against SARS-CoV-2. It emphasizes the importance of these proteins in controlling viral replication and spread. Furthermore, we explore methodological approaches for the identification of ISGs and conduct a comparative analysis with other viruses. Deciphering the roles of ISGs and their interactions with viral pathogens can help identify novel targets for antiviral therapies and enhance our preparedness to confront current and future viral threats.

Citing Articles

Diverse effects of coronavirus-defective viral genomes on the synthesis of IFNβ and ISG15 mRNAs and coronavirus replication.

Hsu H, Chang L, Yang C, Lin C, Teng Y, Hsu P Virol J. 2025; 22(1):37.

PMID: 39953551 PMC: 11827481. DOI: 10.1186/s12985-025-02654-5.

References

Lu J, Pan Q, Rong L, He W, Liu S, Liang C . The IFITM proteins inhibit HIV-1 infection. J Virol. 2010; 85(5):2126-37. PMC: 3067758. DOI: 10.1128/JVI.01531-10. View

Schoggins J, Rice C . Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol. 2012; 1(6):519-25. PMC: 3274382. DOI: 10.1016/j.coviro.2011.10.008. View

Huang I, Bailey C, Weyer J, Radoshitzky S, Becker M, Chiang J . Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog. 2011; 7(1):e1001258. PMC: 3017121. DOI: 10.1371/journal.ppat.1001258. View

Schreiber G . The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19. Front Immunol. 2020; 11:595739. PMC: 7561359. DOI: 10.3389/fimmu.2020.595739. View

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Schoggins J, Wilson S, Panis M, Murphy M, Jones C, Bieniasz P . A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011; 472(7344):481-5. PMC: 3409588. DOI: 10.1038/nature09907. View

Van Damme N, Goff D, Katsura C, Jorgenson R, Mitchell R, Johnson M . The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe. 2008; 3(4):245-52. PMC: 2474773. DOI: 10.1016/j.chom.2008.03.001. View

Wang S, Huang K, Wang C . BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface. Virology. 2014; 449:287-96. PMC: 7111910. DOI: 10.1016/j.virol.2013.11.030. View

Maillet S, Fernandez J, Decourcelle M, El Koulali K, Blanchet F, Arhel N . Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner. Viruses. 2020; 12(6). PMC: 7354551. DOI: 10.3390/v12060636. View

10.

Taylor J, Coleman C, Postel S, Sisk J, Bernbaum J, Venkataraman T . Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. J Virol. 2015; 89(23):11820-33. PMC: 4645327. DOI: 10.1128/JVI.02274-15. View

11.

Schoggins J, Dorner M, Feulner M, Imanaka N, Murphy M, Ploss A . Dengue reporter viruses reveal viral dynamics in interferon receptor-deficient mice and sensitivity to interferon effectors in vitro. Proc Natl Acad Sci U S A. 2012; 109(36):14610-5. PMC: 3437900. DOI: 10.1073/pnas.1212379109. View

12.

Sa Ribero M, Jouvenet N, Dreux M, Nisole S . Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020; 16(7):e1008737. PMC: 7390284. DOI: 10.1371/journal.ppat.1008737. View

13.

Bick M, Carroll J, Gao G, Goff S, Rice C, MacDonald M . Expression of the zinc-finger antiviral protein inhibits alphavirus replication. J Virol. 2003; 77(21):11555-62. PMC: 229374. DOI: 10.1128/jvi.77.21.11555-11562.2003. View

14.

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

15.

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. PMC: 7188648. DOI: 10.1016/j.antiviral.2020.104811. View

16.

Jia B, Serra-Moreno R, Neidermyer W, Rahmberg A, Mackey J, Fofana I . Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog. 2009; 5(5):e1000429. PMC: 2673686. DOI: 10.1371/journal.ppat.1000429. View

17.

Samuel C . Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease. J Biol Chem. 2023; 299(8):104960. PMC: 10290182. DOI: 10.1016/j.jbc.2023.104960. View

18.

Wei J, Stoesser N, Matthews P, Khera T, Gethings O, Diamond I . Risk of SARS-CoV-2 reinfection during multiple Omicron variant waves in the UK general population. Nat Commun. 2024; 15(1):1008. PMC: 10837445. DOI: 10.1038/s41467-024-44973-1. View

19.

Shi Y, Simpson S, Chen Y, Aull H, Benjamin J, Serra-Moreno R . Mutations accumulated in the Spike of SARS-CoV-2 Omicron allow for more efficient counteraction of the restriction factor BST2/Tetherin. PLoS Pathog. 2024; 20(1):e1011912. PMC: 10798645. DOI: 10.1371/journal.ppat.1011912. View

20.

Prelli Bozzo C, Nchioua R, Volcic M, Koepke L, Kruger J, Schutz D . IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro. Nat Commun. 2021; 12(1):4584. PMC: 8319209. DOI: 10.1038/s41467-021-24817-y. View