Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

Hachim, Mahmood Y.; Heialy, Saba Al; Hachim, Ibrahim Y.; Halwani, Rabih; Senok, Abiola; Maghazachi, Azzam A.; Hamid, Qutayba

doi:10.3389/fimmu.2020.01372

Cited by 72 publications

(76 citation statements)

References 38 publications

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“…Given SARS-CoV-2 infection of barrier cells, we thus wondered whether astrocytes would exhibit similar hallmarks of inflammation with concomitant consequences for neuronal health. We indeed observed hallmarks of astrogliosis 87 and viral defense 50 in upregulated GFAP and IFITM3 expression, as well as neurotoxicity in the secreted factor CHI3L1 88–90 (Fig. 3b, Fig.…”

Section: Potential Synaptic Dysfunction Specifically In Layer 2/3 Excmentioning

confidence: 56%

“…3b). IFITM3 serves as the first line of defense against viral infection 49 and its upregulation is a marker of SARS-CoV-2 infection across publicly available datasets 50 . We also observed in the cortex parenchyma a consistent upregulation of the newly described viral entry receptor NRP1 41,51,52 (Fig.…”

Section: Sars-cov-2 Accumulation In Barrier Cells Stimulates Inflammamentioning

confidence: 99%

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Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19

Yang

Kern

et al. 2020

Preprint

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Though SARS-CoV-2 primarily targets the respiratory system, it is increasingly appreciated that patients may suffer neurological symptoms of varied severity. However, an unbiased understanding of the molecular processes across brain cell types that could contribute to these symptoms in COVID-19 patients is still missing. Here, we profile 47,678 droplet-based single-nucleus transcriptomes from the frontal cortex and choroid plexus across 10 non-viral, 4 COVID-19, and 1 influenza patient. We complement transcriptomic data with immunohistochemical staining for the presence of SARS-CoV-2. We find that all major cortex parenchymal and choroid plexus cell types are affected transcriptionally with COVID-19. This arises, in part, from SARS-CoV-2 infection of the cortical brain vasculature, meninges, and choroid plexus, stimulating increased inflammatory signaling into the brain. In parallel, peripheral immune cells infiltrate the brain, microglia activate programs mediating the phagocytosis of live neurons, and astrocytes dysregulate genes involved in neurotransmitter homeostasis. Among neurons, layer 2/3 excitatory neurons--evolutionarily expanded in humans--show a specific downregulation of genes encoding major SNARE and synaptic vesicle components, predicting compromised synaptic transmission. These perturbations are not observed in terminal influenza. Many COVID-19 gene expression changes are shared with those in chronic brain disorders and reside in genetic variants associated with cognitive function, schizophrenia, and depression. Our findings and public dataset provide a molecular framework and new opportunities to understand COVID-19 related neurological disease.

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Section: Potential Synaptic Dysfunction Specifically In Layer 2/3 Excmentioning

confidence: 56%

Section: Sars-cov-2 Accumulation In Barrier Cells Stimulates Inflammamentioning

confidence: 99%

Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19

Yang

Kern

et al. 2020

Preprint

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“…This may be due to association with the activation of the cytokine storm in infected patients during immune response (Gao et al, 2020;Huang et al, 2020;Ruan et al, 2020). Nevertheless, Hachim et al (2020) also reported an early upregulation of IFITM3 in SARS-CoV-2 infected patients. Taken together, the roles in the infection played by these commonly expressed genes at a critical site -possibly the entry route of viral-host interaction in the nasopharynx raises the possibility of low invasive tests to investigate these genes in peripheral blood and support personalized medicine.…”

Section: Discussionmentioning

confidence: 94%

“…In this study, the soluble levels of IFN-I were not addressed, but a possible counterbalance played by upregulation of anti-inflammatory signalling by IL-10 could be in line to what was observed by Blanco-Melo and colleagues (2020). Hachim et al (2020) also reported that genes, especially the IFITM3 gene, involved in IFN response to a viral infection such as type 1 interferon signalling pathway, were upregulated in SARS-CoV-2 infected lung epithelial cells. This further elucidates the release of IFN by the innate immune system in response to viral RNAs, such as is the case with SARS-CoV-2 (Nelemans & Kikkert, 2019).…”

Section: Discussionmentioning

confidence: 95%

Transcriptomic dysregulations associated with SARS-CoV-2 infection in human nasopharyngeal and peripheral blood mononuclear cells

Melo

Bhuiyan

Gatua

et al. 2020

Preprint

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IntroductionOver 24 million people have been infected globally with the novel coronavirus, SARS-CoV-2, with more than 820,000 succumbing to the resulting COVID-19 disease as of the end of August 2020. The molecular mechanisms underlying the pathogenesis of the disease are not completely elucidated. Thus, we aim to understand host response to SARS-CoV-2 infection by comparing samples collected from two distinct compartments (infection site and blood), obtained from COVID-19 subjects and healthy controls.MethodsWe used two publicly available gene expression datasets generated via RNA sequencing in two different samples; nasopharyngeal swabs and peripheral blood mononuclear cells (PBMCs). We performed a differential gene expression analysis between COVID-19 subjects and healthy controls in the two datasets and then functionally profiled their differentially expressed genes (DEGs). The genes involved in innate immunity were also determined.ResultsWe found a clear difference in the host response to SARS-CoV-2 infection between the two sample groups. In COVID-19 subjects, the nasopharyngeal sample group indicated upregulation of genes involved in cytokine activity and interferon signalling pathway, as well as downregulation of genes involved in oxidative phosphorylation and viral transcription. Host response in COVID-19 subjects for the PBMC group, involved upregulation of genes involved in the complement system and immunoglobulin mediated immune response. CXCL13, GABRE, IFITM3 were upregulated and HSPA1B was downregulated in COVID-19 subjects in both sample groups.ConclusionOur results indicate the host response to SARS-CoV-2 is compartmentalized and suggests potential biomarkers of response to SARS-CoV-2 infection.HighlightsTranscriptomic profiling from publicly available RNA-seq count data revealed a site-specific immune response in COVID-19.Host response was found cellular-mediated in nasopharyngeal samples and humoral-mediated in PBMCs samples.CXCL13, GABRE and IFITM3 commonly upregulated and HSPA1B downregulated in both sample groups highlights the potential of these molecules as markers of response to SARS-CoV-2 infection.

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“…We used GEOquery and limma R packages through the GEO2R tool for each dataset (22). We selected the differentially expressed probes, as previously described (23). Briefly, we sorted the genes related to the filtered probes according to the False Discovery Rate (FDR) and selected the top 2,000 differentially expressed probes with FDR <0.05 from each dataset.…”

Section: Degsmentioning

confidence: 99%

Molecular Basis of Cardiac and Vascular Injuries Associated With COVID-19

Hachim

Heialy

Senok

et al. 2020

Front. Cardiovasc. Med.

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Background: Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by the novel coronavirus SARS-CoV-2. The presence of the pre-existing cardiac disease is associated with an increased likelihood of severe clinical course and mortality in patients with COVID-19. Besides, current evidence indicates that a significant number of patients with COVID-19 also exhibit cardiovascular involvement even in the absence of known cardiac risk factors. Therefore, there is a need to understand the underlying mechanisms and genetic predispositions that explain cardiovascular involvement in COVID-19. Objectives: In silico analysis of publicly available datasets to decipher the molecular basis, potential pathways, and the role of the endothelium in the pathogenesis of cardiac and vascular injuries in COVID-19. Materials and Methods: Consistent significant differentially expressed genes (DEGs) shared by endothelium and peripheral immune cells were identified in five microarray transcriptomic profiling datasets in patients with venous thromboembolism "VTE," acute coronary syndrome, heart failure and/or cardiogenic shock (main cardiovascular injuries related to COVID-19) compared to healthy controls. The identified genes were further examined in the publicly available transcriptomic dataset for cell/tissue specificity in lung tissue, in different ethnicities and in SARS-CoV-2 infected vs. mock-infected lung tissues and cardiomyocytes. Results: We identified 36 DEGs in blood and endothelium known to play key roles in endothelium and vascular biology, regulation of cellular response to stress as well as endothelial cell migration. Some of these genes were upregulated significantly in SARS-CoV-2 infected lung tissues. On the other hand, some genes with cardioprotective functions were downregulated in SARS-CoV-2 infected cardiomyocytes. Conclusion: In conclusion, our findings from the analysis of publicly available transcriptomic datasets identified shared core genes pertinent to cardiac and vascular-related injuries and their probable role in genetic susceptibility to cardiovascular injury in patients with COVID-19.

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Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells

Cited by 72 publications

References 38 publications

Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19

Broad transcriptional dysregulation of brain and choroid plexus cell types with COVID-19

Transcriptomic dysregulations associated with SARS-CoV-2 infection in human nasopharyngeal and peripheral blood mononuclear cells

Molecular Basis of Cardiac and Vascular Injuries Associated With COVID-19

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