Interfering with SARS-CoV-2: are interferons friends or foes in COVID-19?

Zanoni, Ivan

doi:10.1016/j.coviro.2021.08.004

Cited by 38 publications

(31 citation statements)

References 97 publications

(95 reference statements)

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“…Compromised activation of type I IFN responses in SARS-CoV-2 patients are associated with disease severity. However, other studies have shown increased IFN activation to be associated with exacerbated COVID-19 21 .…”

Section: Introductionmentioning

confidence: 90%

Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome

Masood

Yameen

Ashraf

et al. 2021

Sci Rep

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Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across the COVID-19 disease spectrum, we found type I interferon (IFN) responses to be significantly upregulated (IFNAR2, IRF2BP1, IRF4, MAVS, SAMHD1, TRIM1), or downregulated (SOCS3, IRF2BP2, IRF2BPL) in Asymptomatic as compared with mild and severe COVID-19, with the dysregulation of an increasing number of ISGs associated with progressive disease. These data suggest that initial early responses against SARS-CoV-2 may be effectively controlled by ISGs. Therefore, we hypothesize that treatment with type I interferons in the early stage of COVID-19 may limit disease progression by limiting SARS-CoV-2 in the host.

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Section: Introductionmentioning

confidence: 90%

Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome

Masood

Yameen

Ashraf

et al. 2021

Sci Rep

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“…In infected cells, the host lncRNAs might modulate IFN induction for antiviral response by interacting with different components in the IFN induction pathway (reviewed [8,132]). Deregulation of the IFN pathways either by inborn errors or the generation of autoantibodies against type I IFNs or deregulation IFN signaling pathways have been associated with COVID-19 pathogenesis [133][134][135]. JAK-STAT signaling pathway in response to viral infection, in general, is the important component of the interferon response of the host.…”

Section: Mechanism Of Deregulation Of Lncrna and Pcgmentioning

confidence: 99%

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

Saha

Laha

Chatterjee

et al. 2021

ncRNA

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Altered expression of protein coding gene (PCG) and long non-coding RNA (lncRNA) have been identified in SARS-CoV-2 infected cells and tissues from COVID-19 patients. The functional role and mechanism (s) of transcriptional regulation of deregulated genes in COVID-19 remain largely unknown. In the present communication, reanalyzing publicly available gene expression data, we observed that 66 lncRNA and 5491 PCG were deregulated in more than one experimental condition. Combining our earlier published results and using different publicly available resources, it was observed that 72 deregulated lncRNA interacted with 3228 genes/proteins. Many targets of deregulated lncRNA could also interact with SARS-CoV-2 coded proteins, modulated by IFN treatment and identified in CRISPR screening to modulate SARS-CoV-2 infection. The majority of the deregulated lncRNA and PCG were targets of at least one of the transcription factors (TFs), interferon responsive factors (IRFs), signal transducer, and activator of transcription (STATs), NFκB, MYC, and RELA/p65. Deregulated 1069 PCG was joint targets of lncRNA and TF. These joint targets are significantly enriched with pathways relevant for SARS-CoV-2 infection indicating that joint regulation of PCG could be one of the mechanisms for deregulation. Over all this manuscript showed possible involvement of lncRNA and mechanisms of deregulation of PCG in the pathogenesis of COVID-19.

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“…Type I and III IFNs may be secreted by almost any cell type, whereas type II IFN production is restricted to immune cells, particularly T and Natural Killer (NK) cells. Innate immunity plays a major role in defending against emerging pathogens like SARS-CoV-2, the causative agent of COVID-19 [7][8][9][10][11]. This respiratory virus has a profound global impact both on a socioeconomic level and as a major threat to human health.…”

Section: Introductionmentioning

confidence: 99%

“…However, despite these evasion mechanisms SARS-CoV-2 still remains sensitive towards all types of IFNs, with types II and III being most effective [12,[16][17][18][19]. Importantly, early induction of high levels of IFNs in patients were reported to prevent severe COVID-19 [8,9]. Conversely, inborn defects in the IFN system or auto-antibodies against type I IFNs are frequently associated with severe disease [10,11].…”

Section: Introductionmentioning

confidence: 99%

The Delta variant of SARS-CoV-2 maintains high sensitivity to interferons in human lung cells

Nchioua¹,

Schundner

Klute³

et al. 2021

Preprint

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Interferons are a major part of the anti-viral innate defense system. Successful pathogens, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), need to overcome these defenses to establish an infection. Early induction of interferons (IFNs) protects against severe coronavirus disease 2019 (COVID-19). In line with this, SARS-CoV-2 is inhibited by IFNs in vitro, and IFN-based therapies against COVID-19 are investigated in clinical trials. However, SARS-CoV-2 continues to adapt to the human population resulting in the emergence of variants characterized by increased transmission fitness and/or decreased sensitivity to preventive or therapeutic measures. It has been suggested that the efficient spread of these so-called “Variants of Concern” (VOCs) may also involve reduced sensitivity to IFNs. Here, we examined whether the four current VOCs (Alpha, Beta, Gamma and Delta) differ in replication efficiency or IFN sensitivity from an early isolate of SARS-CoV-2. All viruses replicated in a human lung cell line and in iPSC-derived alveolar type II cells (iAT2). The Delta variant showed accelerated replication kinetics and higher infectious virus production compared to the early 2020 isolate. Replication of all SARS-CoV-2 VOCs was reduced in the presence of exogenous type I, II and III IFNs. On average, the Alpha variant was the least susceptible to IFNs and the Alpha, Beta and Gamma variants show increased resistance against type III IFN. Although the Delta variant has outcompeted all other variants in humans it remained as sensitive to IFNs as an early 2020 SARS-CoV-2 isolate. This suggests that increased replication fitness rather than IFN resistance may be a reason for its dominance. Our results may help to understand changes in innate immune susceptibility of VOCs, and inform clinical trials exploring IFN-based COVID-19 therapies.

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Interfering with SARS-CoV-2: are interferons friends or foes in COVID-19?

Abstract: Graphical abstract

Cited by 38 publications

References 97 publications

Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome

Upregulated type I interferon responses in asymptomatic COVID-19 infection are associated with improved clinical outcome

Co-Regulation of Protein Coding Genes by Transcription Factor and Long Non-Coding RNA in SARS-CoV-2 Infected Cells: An In Silico Analysis

The Delta variant of SARS-CoV-2 maintains high sensitivity to interferons in human lung cells

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