Type I interferons and SARS-CoV-2: from cells to organisms

doi:10.1016/j.coi.2022.01.003

Review

. 2022 Feb:74:172-182.

doi: 10.1016/j.coi.2022.01.003. Epub 2022 Jan 25.

Type I interferons and SARS-CoV-2: from cells to organisms

Paul Bastard¹, Qian Zhang², Shen-Ying Zhang², Emmanuelle Jouanguy², Jean-Laurent Casanova³

Affiliations

¹ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France. Electronic address: paul.bastard@institutimagine.org.
² Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
³ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France; Howard Hughes Medical Institute, New York, NY, USA. Electronic address: casanova@rockefeller.edu.

PMID: 35149239
PMCID: PMC8786610
DOI: 10.1016/j.coi.2022.01.003

Review

Type I interferons and SARS-CoV-2: from cells to organisms

Paul Bastard et al. Curr Opin Immunol. 2022 Feb.

. 2022 Feb:74:172-182.

doi: 10.1016/j.coi.2022.01.003. Epub 2022 Jan 25.

Authors

Paul Bastard¹, Qian Zhang², Shen-Ying Zhang², Emmanuelle Jouanguy², Jean-Laurent Casanova³

Affiliations

¹ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France. Electronic address: paul.bastard@institutimagine.org.
² Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
³ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, Paris, France; Howard Hughes Medical Institute, New York, NY, USA. Electronic address: casanova@rockefeller.edu.

PMID: 35149239
PMCID: PMC8786610
DOI: 10.1016/j.coi.2022.01.003

Abstract

Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro. In various animal species infected in vivo, type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.

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Figures

**Figure 1**
Life-threatening COVID-19 can be caused in Humans by inborn errors of type I IFN immunity or autoantibodies neutralizing type I IFNs. Both mechanisms interfering with type I IFN immunity in respiratory epithelial cells and blood plasmacytoid dendritic cells. SARS-CoV-2 can replicate in respiratory epithelial cells (REC), but not in pDC which is why the responsive pathway is only shown in REC, where anti-viral ISG will matter, while the self-amplification loop of type I IFN does probably also operate in pDCs. Monogenic inborn errors of type I IFN immunity are shown in red. Auto-Abs to type I IFNs are shown in red. SARS-CoV-2 proteins which can inhibit proteins of the type I IFN pathway are shown in blue. Type I IFNs are shown in blue circles. IFN: interferon; Auto-Ab: autoantibody, ISGs: interferon-stimulated genes.

**Figure 2**
Odds Ratios for critical disease in SARS-CoV-2-infected individuals with auto-Abs against type I IFNs. Odds ratios (OR) and P-values were estimated by means of Firth’s bias-corrected logistic regression.

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References

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1. Theves C., Crubezy E., Biagini P. History of smallpox and its spread in human populations. Microbiol Spectr. 2016;4 - PubMed
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1. Worldometer . vol 2021. 2021. (COVID-19 Coronavirus Pandemic).

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[1] Hoffmann H.H., Schneider W.M., Rice C.M. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol. 2015;36:124–138. - PMC - PubMed

[2] Hoffmann H.H., Schneider W.M., Rice C.M. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol. 2015;36:124–138. - PMC - PubMed

[3] Theves C., Crubezy E., Biagini P. History of smallpox and its spread in human populations. Microbiol Spectr. 2016;4 - PubMed

[4] Theves C., Crubezy E., Biagini P. History of smallpox and its spread in human populations. Microbiol Spectr. 2016;4 - PubMed

[5] Breitbart M., Rohwer F. Here a virus, there a virus, everywhere the same virus? Trends Microbiol. 2005;13:278–284. - PubMed

[6] Breitbart M., Rohwer F. Here a virus, there a virus, everywhere the same virus? Trends Microbiol. 2005;13:278–284. - PubMed

[7] Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. - PMC - PubMed

[8] Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., Si H.R., Zhu Y., Li B., Huang C.L., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–273. - PMC - PubMed

[9] Worldometer . vol 2021. 2021. (COVID-19 Coronavirus Pandemic).

[10] Worldometer . vol 2021. 2021. (COVID-19 Coronavirus Pandemic).

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Type I interferons and SARS-CoV-2: from cells to organisms

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Type I interferons and SARS-CoV-2: from cells to organisms

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