Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections

Thair, Simone A.; He, Yudong; Hasin-Brumshtein, Yehudit; Sakaram, Suraj; Pandya, Rushika; Toh, Jiaying; Rawling, David; Remmel, Melissa; Coyle, Sabrina; Dalekos, George Ν.; Koutsodimitropoulos, Ioannis; Vlachogianni, Glykeria; Gkeka, Eleni; Karakike, Eleni; Damoraki, Georgia; Antonakos, Nikolaos; Khatri, Purvesh; Giamarellos‐Bourboulis, Evangelos J.; Sweeney, Timothy E.

doi:10.1101/2020.06.18.20131326

Cited by 11 publications

(14 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CHUK encodes for IKK-alpha which is a critical component in regulation of the NF-κB signaling pathway, a transcriptional complex commonly activated by viral infections that regulates diverse events including proinflammatory cytokine production and cell survival (Santoro et al, 2003; Taniguchi and Karin, 2018). NFE2 is a transcription factor regulating diverse cellular responses, including cell differentiation, and has been shown to be upregulated in response to SARS-CoV-2 infection (Gasiorek and Blank, 2015; Thair et al, 2021). TRAF3IP2 encodes for ACT1, an adaptor protein possessing E3-ubiquitin ligase activity involved in IL-17 and NF-κB signaling pathways (Li et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Biering

Sarnik

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

SUMMARYSARS-CoV-2 can cause a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of the host factors mediating viral infection or restriction is critical to elucidate SARS-CoV-2 host-pathogen interactions and the progression of COVID-19. To this end, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. These screens uncovered proviral and antiviral host factors across highly interconnected host pathways, including components implicated in clathrin transport, inflammatory signaling, cell cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high-molecular weight glycoproteins, as a prominent viral restriction network. We demonstrate that multiple membrane-anchored mucins are critical inhibitors of SARS-CoV-2 entry and are upregulated in response to viral infection. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and suggests interactions between SARS-CoV-2 and airway mucins of COVID-19 patients as a host defense mechanism.

show abstract

Section: Resultsmentioning

confidence: 99%

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Biering

Sarnik

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, many signatures are likely to reflect general immune and inflammatory responses. We plan to include studies on other viral infections (such as SARS-CoV and influenza) to identify unique metabolic signatures of this disease as illustrated in a recent meta-analysis based on transcriptomics [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Meta-Analysis of COVID-19 Global Metabolomics Datasets

et al. 2021

View full text Add to dashboard Cite

The novel coronavirus SARS-CoV-2 has spread across the world since 2019, causing a global pandemic. The pathogenesis of the viral infection and the associated clinical presentations depend primarily on host factors such as age and immunity, rather than the viral load or its genetic variations. A growing number of omics studies have been conducted to characterize the host immune and metabolic responses underlying the disease progression. Meta-analyses of these datasets have great potential to identify robust molecular signatures to inform clinical care and to facilitate therapeutics development. In this study, we performed a comprehensive meta-analysis of publicly available global metabolomics datasets obtained from three countries (United States, China and Brazil). To overcome high heterogeneity inherent in these datasets, we have (a) implemented a computational pipeline to perform consistent raw spectra processing; (b) conducted meta-analyses at pathway levels instead of individual feature levels; and (c) performed visual data mining on consistent patterns of change between disease severities for individual studies. Our analyses have yielded several key metabolic signatures characterizing disease progression and clinical outcomes. Their biological interpretations were discussed within the context of the current literature. To the best of our knowledge, this is the first comprehensive meta-analysis of global metabolomics datasets of COVID-19.

show abstract

“…We curated RNA-seq based molecular signatures related to IBD and COVID-19 response by identifying differentially expressed genes (DEGs) as detailed in supplementary methods. Genes found differentially expressed in blood 48 , lung NHBE/A549 31 or human small intestinal organoids 34 (hSIO) following SARS-CoV-2 infection; IBD inflammation; or response to medications were separately projected onto various BGRNs allowing for 1 or 2 nearest neighbors depending on the signature sizes.…”

Section: Ibd Inflammation Covid-19 and Ibd Drug Response-subnetwork mentioning

confidence: 99%

Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease

Suárez‐Fariñas

Tokuyama

Wei

et al. 2020

Preprint

View full text Add to dashboard Cite

Immune dysregulation and cytokine release syndrome have emerged as pathological hallmarks of severe Coronavirus Disease 2019 , leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed therapies being considered for COVID-19 patients are already in clinical use in chronic inflammatory conditions like inflammatory bowel disease (IBD). These considerations led us to systematically examine the intersections between COVID-19 and the GI tract during health and intestinal inflammation. We have observed that IBD medications, both biologic and nonbiologic, do not significantly impact ACE2 and TMPRSS2 expression in the uninflamed intestines.Additionally, by comparing SARS CoV2-induced epithelial gene signatures with IBD-associated genes, we have identified a shared molecular subnetwork between COVID-19 and IBD. These data generate a novel appreciation of the confluence of COVID-19-and IBD-associated inflammation and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19. nearest neighbor. The most connected subnetworks were then extracted to generate model-specific SARS-CoV-2 infection-; IBD inflammation-; or drug-response associated subnetworks. Genes common between these networks were determined and tested for enrichment to various genesets using the Fisher's exact test and p-values were adjusted using Benjamini-Hochberg (BH) procedure. Pathway and geneset enrichment analysis of subnetworks:Gene subnetworks were tested for functional enrichment using a Fisher's exact test with BH multiple test correction on a collection of gene sets. The collection of gene sets included i) Reactome pathways sourced from Enrichr 31 , i) genesets from Smillie et al 32 , ii) Huang et al 33 , iii) various macrophage perturbations (e.g. cytokines) 34 , iv) ACE2 co-expressed genes 35 and v) reported IBD GWAS genes (see supplementary methods). Key driver gene analysis:7 Key driver analysis (KDA) identifies key or "master" driver genes for a given gene set in a given BGRN. We used a previously described KDA algorithm 36 which is summarized in supplementary methods.Genesets for KDA included those associated with NHBE-COVID-19 infection or IBD inflammation. Key driver genes (KDGs) were summarized by frequency across the networks/genesets tested. Geneset variation analysis of SARS-CoV-2-infection gene expression signatures:We employed the epithelial model-COVID-19 response gene signatures (adjusted p value <0.05) in a gene set variation analysis (GSVA) using gene expression data from MSCCR and CERTIFI cohorts. For each gene set (up or down-regulated), GSVA was used to obtain a sample-wise enrichment score, that were then used for hypothesis testing with respect to phenotype information.

show abstract

Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections

Cited by 11 publications

References 53 publications

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Comprehensive Meta-Analysis of COVID-19 Global Metabolomics Datasets

Intestinal inflammation modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease

Contact Info

Product

Resources

About