Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection

Bińkowski, Jan; Taryma-Leśniak, Olga; Łuczkowska, Karolina; Niedzwiedź, Anna Anna; Lechowicz, Kacper; Strapagiel, Dominik; Jarczak, Justyna; Dávalos, Verónica; Pujol, Aurora; Esteller, Manel; Kotfis, Katarzyna; Machaliński, Bogusław; Parczewski, Miłosz; Wojdacz, Tomasz K.

doi:10.1016/j.biopha.2022.113396

Cited by 6 publications

(7 citation statements)

References 59 publications

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“…Infections and inflammation impact all steps in the production, control, and modification of new proteins and SARS-CoV2 has a direct impact on protein translation, and protein trafficking 76 , and need post translational modifications 77 . Regarding neurological effects of COVID-19 there are reports that have demonstrated direct effects on the nervous system and connection between long COVID-19 78,79 and exploring our data set's matches with other data sets revealed mutual enrichment of six genes, i.e., OAS1, CXCR5, APP, CCL20, CNR2, and C3AR1 10,51,52,53,54,80,81,82,83,84 . The enriched top terms defined by the analysis match included regulation of cell activation, leukocyte activation, inflammatory response, regulation of immune effector processes, and neutrophil degranulation.…”

Section: Discussionmentioning

confidence: 57%

Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients

Govender,

Das,

Hopkins

et al. 2024

Preprint

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The emergence of SARS-CoV-2 has had a profound adverse impact on global health and continues to remain a threat worldwide. The disease spectrum of COVID-19 ranges from asymptomatic to fatal clinical outcomes especially in the elderly population and in individuals with underlying medical conditions. The impact of COVID-19 on host immune responses and immune cells at the protein and DNA levels remains largely ambiguous. In a case-control study, here we explored the impact of COVID-19 on DNA methylation patterns in the upper respiratory airway to determine how SARS-CoV-2 infection altered the immune status of individuals requiring hospitalization for COVID-19. We performed DNA methylation arrays on nasopharyngeal swabs at inclusion/hospitalization as well as 6 weeks post-inclusion. Our study reveals a distinct DNA methylation pattern in COVID-19 patients compared to healthy controls, characterized by 317 779 differentially methylated CpGs. Notably, within the transcription start sites and gene body, COVID-19 patients exhibited a higher number of genes/CpGs with elevated methylation levels. Enrichment analysis of methylated genes at transcription start sites highlighted the impact on genes associated with inflammatory responses and immune functions. Some SARS-CoV-2 -induced CpG methylations were transient, returning to normal levels by 6 weeks post-inclusion. Enriched genes of interest included IL-17A, a pivotal cytokine implicated with inflammation and healing, and NUP93, associated with antiviral innate immunity. Further, six genes in our data set, OAS1, CXCR5, APP, CCL20, CNR2, and C3AR1, were found in enrichment analysis with previous COVID-19 studies. Additionally, RNAse1 and RNAse2 emerged as key regulators, while IL-18 played a role in various biological processes in COVID-19 patients. Overall, our results demonstrates that COVID-19 has a major impact on the upper airway by modifying the methylation pattern of many genes and this could have implications for the conditioning of the airways and how the individual response to future airway infections.

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Section: Discussionmentioning

confidence: 57%

Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients

Govender,

Das,

Hopkins

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…In total, 733,236 probes passed QC. No statistically significant differences between analyzed samples were detected with the EpiDISH R package modified as described in 15 and none of the processed microarrays was a technical outlier according to MethylAid package 16 . The R version 4.1.3 was used for data processing and statistics calculation.…”

Section: Methodsmentioning

confidence: 99%

Analytical sensitivity of a method is critical in detection of low-level BRCA1 constitutional epimutation

Machaj,

Sokolowska,

Borowski

et al. 2023

Sci Rep

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Recent reports based on a substantial number of cases, warrant need for population-based research to determine implications of constitutional methylation of tumor suppressor genes such as BRCA1 occurring in healthy tissue in the prediction of cancer. However, the detection of the constitutional methylation in DNA extracted from blood has already been shown to be technologically challenging, mainly because epimutations appear to be present in blood at a very low level. The analytical sensitivity required for low-level methylation detection can be provided by NGS, but this technique is still labor and cost-intensive. We assessed if PCR-based MS-HRM and BeadChip microarray technologies, which are standardized and cost-effective technologies for methylation changes screening, provide a sufficient level of analytical sensitivity for constitutional BRCA1 methylation detection in blood samples. The study included whole blood samples from 67 healthy women, 35 with previously confirmed and 32 with no detectable BRCA1 promoter methylation for which we performed both MS-HRM based BRCA1 gene methylation screening and genome wide methylation profiling with EPIC microarray. Our results shown, that low-level BRCA1 methylation can be effectively detected in DNA extracted from blood by PCR-based MS-HRM. At the same time, EPIC microarray does not provide conclusive results to unambiguously determine the presence of BRCA1 constitutional methylation in MS-HRM epimutation positive samples. The analytical sensitivity of MS-HRM is sufficient to detect low level BRCA1 constitutional epimutation in DNA extracted from blood and BeadChip technology-based microarrays appear not to provide that level of analytical sensitivity.

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“…Possible explanations for the lower IFN-I mRNA levels in LC children could be a more rapid decline of IFN-I during LC, as observed during the acute phase of the SARS-CoV-2 infection when children mount a more transient innate antiviral response than adults [37], or a functional impairment of plasmacytoid dendritic cells during infection, which are a major source of IFN-I expression [38]. Furthermore, differences in IFN-I expression could be influenced by immune cell proportions and epigenetic signatures, which differ between children, adolescents, and adults [39][40][41]. Our findings in LC adolescents may be consistent with what has been described in LC adults, where one study showed elevated serum IFN-β protein concentrations 4 months after SARS-CoV-2 infection compared with unexposed healthy donors [42].…”

Section: Discussionmentioning

confidence: 99%

Age‐related transcript changes in type I interferon signaling in children and adolescents with long COVID

Fracella,

Mancino,

Nenna

et al. 2024

Eur J Immunol

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SARS‐CoV‐2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN‐I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age‐matched SARS‐CoV‐2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN‐I (IFN‐α/β/ε/ω), IFN‐I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3–6 months after COVID‐19. LC adolescents (12–17 years) had higher transcript levels of IFN‐β, IFN‐ε, and IFN‐ω than HC, whereas LC children (6–11 years) had lower levels than HC. In adolescents, increased levels of IFN‐α, IFN‐β, and IFN‐ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN‐α/β mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age‐related changes in the expression of transcripts involved in the IFN‐I signaling pathway in children and adolescents with LC.

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Epigenetic activation of antiviral sensors and effectors of interferon response pathways during SARS-CoV-2 infection

Cited by 6 publications

References 59 publications

Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients

Altered DNA methylation pattern contributes to differential epigenetic immune signaling in the upper respiratory airway of COVID-19 patients

Analytical sensitivity of a method is critical in detection of low-level BRCA1 constitutional epimutation

Age‐related transcript changes in type I interferon signaling in children and adolescents with long COVID

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