Abstract:Host miRNAs are known to modulate the cell response to virus infections. We characterized the miRNA-targeted transcriptome of porcine alveolar macrophages (PAMs) at early times after infection with a subtype 1.1 strain of PRRSV (Porcine Reproductive and Respiratory Syndrome Virus). We performed the immunoprecipitation of RISC (RNA-induced Silencing Complex) followed by microarray analysis of the RISC-bound miRNA targets (RIP-Chip) to evaluate the relative enrichment or depletion of expressed genes in RISC. The… Show more
“…miR-335-5p had the most predicted targets in the response against the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) of alveolar macrophages. Contrastingly, no effects on the cytokine expression was observed in this study (Dhorne-Pollet et al . 2019).…”
Background: Coronavirus disease 2019 is characterized by the elevation of a wide spectrum of inflammatory mediators which are associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future.
Methods: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and GEO microarray dataset and their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, and Gene Ontology, and pathways predicted by KEGG and Reactome pathways. The functional and regulatory features were analyzed and visualized through Cytoscape.
Results: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded 10 miRNAs that are significantly involved in the regulation of these genes and their transcription factors.
Conclusion: An In-Silico representation of a network involving miRNAs, CRIEGs, and TF which take part in the inflammatory response in COVID-19 has been elucidated. These regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further for the development of targeted therapeutic strategies and mechanistic validation.
“…miR-335-5p had the most predicted targets in the response against the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) of alveolar macrophages. Contrastingly, no effects on the cytokine expression was observed in this study (Dhorne-Pollet et al . 2019).…”
Background: Coronavirus disease 2019 is characterized by the elevation of a wide spectrum of inflammatory mediators which are associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future.
Methods: The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and GEO microarray dataset and their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, and Gene Ontology, and pathways predicted by KEGG and Reactome pathways. The functional and regulatory features were analyzed and visualized through Cytoscape.
Results: Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded 10 miRNAs that are significantly involved in the regulation of these genes and their transcription factors.
Conclusion: An In-Silico representation of a network involving miRNAs, CRIEGs, and TF which take part in the inflammatory response in COVID-19 has been elucidated. These regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further for the development of targeted therapeutic strategies and mechanistic validation.
“…Out of the remaining 17 differentially expressed miRNAs, miR-20a and hsa-let-7 have been reported to regulate antifungal responses, although only in Paracoccidioides brasiliensis (56). miR-16 and miR-4677 have been linked to antibacterial host responses (57,58), while miR-3074, miR-335, miR-34b, miR-4485, and miR-1246 have been associated with antiviral immune responses in various in vitro models (59)(60)(61)(62)(63). The remaining nine identified miRNA species have not yet been associated with microbe-induced inflammatory responses.…”
Oral epithelial cells monitor microbiome composition and initiate immune response upon dysbiosis, as in the case of Candida imbalances. Candida species, such as C. albicans and C. parapsilosis, are the most prevalent yeasts in the oral cavity. Comparison of healthy oral epithelial cell responses revealed that while C. albicans infection robustly activated inflammation cascades, C. parapsilosis primarily activated various inflammation-independent pathways. In posttranscriptional regulatory processes, several miRNAs were altered by both species. For C. parapsilosis, the dose of yeast cells directly correlated with changes in transcriptomic responses with higher fungal burdens inducing significantly different and broader changes. MicroRNAs (miRNAs) associated with carbohydrate metabolism-, hypoxia-, and vascular development-related responses dominated with C. parapsilosis infection, whereas C. albicans altered miRNAs linked to inflammatory responses. Subsequent analyses of hypoxia-inducible factor 1α (HIF1-α) and hepatic stellate cell (HSC) activation pathways predicted target genes through which miRNA-dependent regulation of yeast-specific functions may occur, which also supported the observed species-specific responses. Our findings suggest that C. parapsilosis is recognized as a commensal at low doses by the oral epithelium; however, increased fungal burden activates different pathways, some of which overlap with the inflammatory processes robustly induced by C. albicans.
IMPORTANCE A relatively new topic within the field of immunology involves the role of miRNAs in innate as well as adaptive immune response regulation. In recent years, posttranscriptional regulation of host-pathogenic fungal interactions through miRNAs was also suggested. Our study reveals that the distinct nature of human oral epithelial cell responses toward C. parapsilosis and C. albicans is possibly due to species-specific fine-tuning of host miRNA regulatory processes. The findings of this study also shed new light on the nature of early host cell transcriptional responses to the presence of C. parapsilosis and highlight the species’ potential inflammation-independent host activation processes. These findings contribute to our better understanding of how miRNA deregulation at the oral immunological barrier, in noncanonical immune cells, may discriminate between fungal species, particularly Candida species with high or low pathogenic potential.
“…A total of 288 miRNAs were identified in the pig endometrium (Hong et al, 2019). Studies have been conducted to determine the host cell-PRRSV interaction networks, and numerous species of miRNAs appear to be altered (Calcatera et al, 2018;Dhorne-Pollet et al, 2019;Hicks et al, 2013;Li et al, 2018;Zhang et al, 2019a), suggesting that host miRNAs indeed modulate PRRSV replication, either positively or negatively. miR-181, miR-23, miR-30c, and miR-24-3p are reported to play important roles in PRRSV replication and in modulating host antiviral responses, while other such as miR-204, miR-221, and miR-219 need more study to understand for their functions .…”
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