COVID-19 and emerging viral infections: The case for interferon lambda

doi:10.1084/jem.20200653

. 2020 May 4;217(5):e20200653.

doi: 10.1084/jem.20200653.

COVID-19 and emerging viral infections: The case for interferon lambda

Ludmila Prokunina-Olsson¹, Noémie Alphonse^{2

3}, Ruth E Dickenson^#², Joan E Durbin^{4

5}, Jeffrey S Glenn^#⁶, Rune Hartmann⁷, Sergei V Kotenko^{5

8

9}, Helen M Lazear¹⁰, Thomas R O'Brien¹¹, Charlotte Odendall², Olusegun O Onabajo¹, Helen Piontkivska¹², Deanna M Santer¹³, Nancy C Reich¹⁴, Andreas Wack³, Ivan Zanoni¹⁵

Affiliations

¹ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
² Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
³ Immunoregulation Laboratory, Francis Crick Institute, London, UK.
⁴ Department of Pathology, Laboratory Medicine and Immunology, Newark, NJ.
⁵ Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
⁶ Departments of Medicine and Microbiology & Immunology, Stanford University School of Medicine, and Palo Alto Veterans Administration, Palo Alto, CA.
⁷ Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
⁸ Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
⁹ Center for Cell Signaling, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
¹⁰ Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
¹¹ Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
¹² Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, PA.
¹³ Li Ka Shing Institute of Virology and Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
¹⁴ Department of Microbiology & Immunology, Stony Brook University, Stony Brook, NY.
¹⁵ Division of Immunology, Division of Gastroenterology, Harvard Medical School, Boston Children's Hospital, Boston, MA.

^# Contributed equally.

PMID: 32289152
PMCID: PMC7155807
DOI: 10.1084/jem.20200653

COVID-19 and emerging viral infections: The case for interferon lambda

Ludmila Prokunina-Olsson et al. J Exp Med. 2020.

. 2020 May 4;217(5):e20200653.

doi: 10.1084/jem.20200653.

Authors

Affiliations

¹ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
² Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, London, UK.
³ Immunoregulation Laboratory, Francis Crick Institute, London, UK.
⁴ Department of Pathology, Laboratory Medicine and Immunology, Newark, NJ.
⁵ Center for Immunity and Inflammation, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
⁶ Departments of Medicine and Microbiology & Immunology, Stanford University School of Medicine, and Palo Alto Veterans Administration, Palo Alto, CA.
⁷ Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
⁸ Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
⁹ Center for Cell Signaling, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, NJ.
¹⁰ Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
¹¹ Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
¹² Department of Biological Sciences, School of Biomedical Sciences, Kent State University, Kent, PA.
¹³ Li Ka Shing Institute of Virology and Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
¹⁴ Department of Microbiology & Immunology, Stony Brook University, Stony Brook, NY.
¹⁵ Division of Immunology, Division of Gastroenterology, Harvard Medical School, Boston Children's Hospital, Boston, MA.

^# Contributed equally.

PMID: 32289152
PMCID: PMC7155807
DOI: 10.1084/jem.20200653

Abstract

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.

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Figures

**Figure 1.**
**Potential benefits of using type III IFNs for prevention and treatment of COVID-19** Type I IFNs (IFN-α/β) signal through a heterodimeric receptor complex, IFNAR, which is comprised of IFNAR1 and IFNAR2 subunits. IFNAR activation induces expression of ISGs and triggers pro-inflammatory responses via the recruitment and activation of immune cells. This promotes an antiviral state in the host, but as IFNAR is expressed on all cells, the administration of type I IFN can have serious systemic side effects. In contrast, type III IFNs (IFN-λ1-4) signal through a distinct receptor complex, IFNLR, which consists of IL10R2 and IFNLR1 subunits. IFNLR1 expression is restricted to epithelial cells and a subset of immune cells, including neutrophils. Therefore, type III IFN administration as a prophylactic treatment or at an early stage of COVID-19 would result in ISG expression and antiviral response localized to epithelial cells, reducing side effects and inflammation associated with the systemic action of type I IFNs.

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References

1. Blazek K., et al. J. Exp. Med. 2015 doi: 10.1084/jem.20140995. - DOI - PubMed
1. Broggi A., et al. Nat. Immunol. 2017 doi: 10.1038/ni.3821. - DOI - PMC - PubMed
1. Broggi A., et al. J. Exp. Med. 2020 doi: 10.1084/jem.20190295. - DOI - PubMed
1. Crotta S., et al. PLoS Pathog. 2013 doi: 10.1371/journal.ppat.1003773. - DOI - PMC - PubMed
1. Davidson S., et al. J. Interferon Cytokine Res. 2015 doi: 10.1089/jir.2014.0227. - DOI - PMC - PubMed

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[1] Blazek K., et al. J. Exp. Med. 2015 doi: 10.1084/jem.20140995. - DOI - PubMed

[2] Blazek K., et al. J. Exp. Med. 2015 doi: 10.1084/jem.20140995. - DOI - PubMed

[3] Broggi A., et al. Nat. Immunol. 2017 doi: 10.1038/ni.3821. - DOI - PMC - PubMed

[4] Broggi A., et al. Nat. Immunol. 2017 doi: 10.1038/ni.3821. - DOI - PMC - PubMed

[5] Broggi A., et al. J. Exp. Med. 2020 doi: 10.1084/jem.20190295. - DOI - PubMed

[6] Broggi A., et al. J. Exp. Med. 2020 doi: 10.1084/jem.20190295. - DOI - PubMed

[7] Crotta S., et al. PLoS Pathog. 2013 doi: 10.1371/journal.ppat.1003773. - DOI - PMC - PubMed

[8] Crotta S., et al. PLoS Pathog. 2013 doi: 10.1371/journal.ppat.1003773. - DOI - PMC - PubMed

[9] Davidson S., et al. J. Interferon Cytokine Res. 2015 doi: 10.1089/jir.2014.0227. - DOI - PMC - PubMed

[10] Davidson S., et al. J. Interferon Cytokine Res. 2015 doi: 10.1089/jir.2014.0227. - DOI - PMC - PubMed

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COVID-19 and emerging viral infections: The case for interferon lambda

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COVID-19 and emerging viral infections: The case for interferon lambda

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