Correction: Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock

Joly, Sophie; Rhea, Lindsey; Volk, Paige; Moreland, Jessica G.; Dunnwald, Martine

doi:10.1371/journal.pone.0171459

Cited by 2 publications

(1 citation statement)

References 1 publication

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“…IRF6 gene is a transcriptional activator with well-established role in the development of the epidermis. A recent study suggests a role for IRF6 in the modulation of the NFk-B-pathway that influences cell-survival by regulating host responses during viral infection, such as cytokine production [49]. AP1G1 (Adaptor Related Protein Complex 1 Subunit Gamma 1) encodes a component of clathrincoated vesicles that were shown to mediate endocytosis and intracellular trafficking of SARS-CoV-2 [50,51].…”

Section: Sars-cov-2 Infectionmentioning

confidence: 99%

CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2

Finkel

Israeli

Beth-Din

et al. 2021

Preprint

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The global spread of SARS-CoV-2 lead to the most challenging pandemic in this century, posing major economic and health challenges worldwide. Revealing host genes essential for infection by multiple variants of SASR-CoV-2 can provide insights into the virus pathogenesis, and facilitates the development of novel broad-spectrum host-directed therapeutics. Here, employing genome-scale CRISPR screens, we provide a comprehensive data-set of cellular factors that are exploited by WT-SARS-CoV-2 as well as two additional recently emerged variants of concerns (VOCs), Alpha and Beta. These screens identified known and novel host factors critical for SARS-CoV-2 infection, including various components belonging to the Clathrin-dependent transport pathway, ubiquitination and Heparan sulfate biogenesis. In addition, the host metabolic pathways pertaining to mitochondrial activity as well as phosphatidylglycerol biosynthesis processes appeared to have major anti-viral functions. Comparative analysis between the different VOCs revealed the receptor KREMEN2 as unique gene required only to the Alpha variant, providing a possible explanation for the increased infectivity of this variant. Furthermore, the analysis identified GATA6, a zinc finger transcription factor, as an essential pro-viral gene for all variants inspected. We reveal that GATA6 directly regulates ACE2 transcription and is accordingly, critical for SARS-CoV-2 cell entry. Analysis of clinical samples collected from SARS-CoV-2 infected individuals showed an elevated level of GATA6, indicating the important role GATA6 may be playing in COVID-19 pathogenesis. Finally, pharmacological inhibition of GATA6 results in down-modulation of ACE2 and consequently to inhibition of the viral infectivity. Overall, we show GATA6 represents a target for the development of anti-SARS-CoV-2 therapeutic strategies and reaffirm the value of the CRISPR loss-of-function screens in providing a list of potential new targets for therapeutic interventions.

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Section: Sars-cov-2 Infectionmentioning

confidence: 99%

CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2

Finkel

Israeli

Beth-Din

et al. 2021

Preprint

View full text Add to dashboard Cite

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Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures

Duggal

Lei

et al. 2023

The Journal of Thoracic and Cardiovascular Surgery

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Correction: Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock

Abstract: In the Funding section, the second grant number from the funder National Institutes of Health is listed incorrectly. The correct grant number is: AR067739.

Cited by 2 publications

References 1 publication

CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2

CRISPR screens for host factors critical for infection by SARS-CoV-2 variants of concern identify GATA6 as a central modulator of ACE2

Mitral regurgitation severity at left ventricular assist device implantation is associated with distinct myocardial transcriptomic signatures

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