SARS-CoV-2/COVID-19 and its relationship with NOD2 and ubiquitination

Rivera, Edgardo Guzman; Patnaik, Asha; Salvemini, Joann; Jain, Sanjeev; Lee, Katherine; Lozeau, Daniel; Yao, Qingping

doi:10.1016/j.clim.2022.109027

Cited by 29 publications

(14 citation statements)

References 57 publications

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“…In contrast, the downregulated genes were related to ribosome pathways. Several studies have demonstrated the important roles of these signaling pathways in either innate immunity or COVID-19 progression, including their utility as diagnostic biomarkers and potential treatment strategies [42][43][44][45][46][47][48]. In addition, we found that some TFs were differentially expressed in severe COVID-19.…”

Section: Severe Covid-19-specific Expression Patterns In Neutrophilsmentioning

confidence: 54%

Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19

Zhang,

Nishi,

Kinoshita

2023

Preprint

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Background: Accumulating evidence has revealed unexpected phenotypic heterogeneity and diverse functions of neutrophils in several diseases. Coronavirus disease (COVID-19) can alter the leukocyte phenotype based on disease severity, including neutrophil activation in severe cases. However, the plasticity of neutrophil phenotypes and their relative impact on COVID-19 pathogenesis has not been well addressed. This study aimed to identify and validate the heterogeneity of neutrophils in COVID-19 and evaluate the phenotypic alterations for each subpopulation. Methods: We analyzed public single-cell RNA-seq, bulk RNA-seq, and human plasma proteome data from healthy donors and patients with COVID-19 to investigate neutrophil subpopulations and their response to disease pathogenesis. Results: We identified eight neutrophil subtypes, namely C1-C8, and found that they exhibited distinct features, including activation signatures and multiple enriched pathways. The neutrophil subtype C4 (DEFA1/1B/3+) associated with severe and fatal disease. Bulk RNA-seq and proteome dataset analyses using a cellular deconvolution approach validated the relative abundances of neutrophil subtypes and the expansion of C4 (DEFA1/1B/3+) in severe COVID-19 patients. Cell-cell communication analysis revealed representative ligand-receptor interactions among the identified neutrophil subtypes. Notably, the C4 (DEFA1/1B/3+) fraction showed transmembrane receptor expression of CD45 and CAP1 as well as the secretion of pro-platelet basic protein (PPBP). We further demonstrated the clinical potential of PPBP as a novel diagnostic biomarker for severe COVID-19. Conclusion: Our work has great value in terms of both clinical and public health as it furthers our understanding of the phenotypic and functional heterogeneity of neutrophils and other cell populations in multiple diseases.

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Section: Severe Covid-19-specific Expression Patterns In Neutrophilsmentioning

confidence: 54%

Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19

Zhang,

Nishi,

Kinoshita

2023

Preprint

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“…For example, aberrant USP29 deubiquitylation could enhance the virulence of SARS-CoV-2 by preventing proteasome degradation of ORF9b ( 34 ). One of the underlying mechanisms why SARS-CoV-2 infection can promote autoinflammatory disease was that SARS-CoV-2 affects UBA1 and ubiquitination in an inappropriate way ( 35 ). Nevertheless, in addition to DNA damage and repair, no findings of cell cycle-associated, and ubiquitination-associated signaling were reported in COVID-19-associated MI, which deserves further exploration.…”

Section: Discussionmentioning

confidence: 99%

Exploration of the common genetic landscape of COVID-19 and male infertility

et al. 2023

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BackgroundCOVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI.Materials and methodsA total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique.ResultsWe identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve > 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups.ConclusionThe present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.

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“…Indeed, in those patients, we identified variants in candidate genes, such as TNFRSF13B , UBA1 , IRF2BP2 , FCN3 , MYOF , CFAP54 , NME8 , and CFAP46 , involved in the immune system response, inflammatory processes, and respiratory infections. In particular, mutations in TNFRSF13B , UBA1 , IRF2BP2, and FCN3 were already reported to be associated with severe COVID-19 [ 39 , 40 , 41 , 42 ]. The MYOF (myoferlin) gene modulates VEGF signal transduction, which has already been shown to play a key role in life-threatening COVID-19 [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Baldassarri

Zguro

Tomati

et al. 2022

Cells

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Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19.

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SARS-CoV-2/COVID-19 and its relationship with NOD2 and ubiquitination

Cited by 29 publications

References 57 publications

Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19

Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19

Exploration of the common genetic landscape of COVID-19 and male infertility

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

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