Project description:This series includes 1 microarray used to detect a human metapneumovirus strain associated with critical respiratory illness in an elderly male with leukemia (Chiu, et al 2006) Keywords: viral detection
Project description:Respiratory viruses pose an ongoing threat to human health, with excessive cytokine secretion playing a critical role in severe illness and mortality. However, the complex relationship between cytokine secretion and viral infection remains poorly understood. Here, we have unraveled the role of cxcl8 as an early response gene to respiratory EV-D68 infection. The upregulation of CXCL8 by viral infection is found to be crucial for EV-D68 replication. Importantly, silencing CXCL8 or its receptors, CXCR1/2, significantly impedes EV-D68 replication. Upon recognition of CXCL8 by CXCR1/2, the MAPK pathway is activated, facilitating the translocation of the essential host cofactor hnRNP K from the nucleus to the cytoplasm. This translocation enhances the recognition of viral RNA by hnRNP K in the cytoplasm, promoting the functionality of the 5’UTR region in the viral genome. Interestingly, the VP4 structural protein of EV-D68 contains a mimic motif of human immunoreceptor tyrosine-based activation motif (ITAM) that interacts with syk and triggers the PI3K/AKT signaling pathway, resulting in elevated CXCL8 gene expression for viral replication. Moreover, our investigations reveal the conservation and significance of the CXCL8 signaling pathway across various prominent human respiratory viruses, including SARS-CoV-2, influenza, and rhinovirus. In summary, our findings unveil a paradigmatic mechanism through which respiratory viruses exploit cytokine-mediated intercellular communication to transmit signals that optimize viral replication. This deepens our understanding of the shared evolutionary strategies employed by respiratory viruses and opens up new avenues for the development of broad-spectrum antiviral drugs targeting respiratory pathogens.
Project description:Human metapneumovirus (HMPV) is a primary causative agent of acute lower respiratory tract infections. We used single cell RNA-sequencing (scRNA-seq) to assess lung immune profiles in a mouse model of HMPV infection.
Project description:Abstract<br>BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has demonstrated to be a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature availble on gene expression markers associated to Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated to critical respiratory illness in this disease is not known to the present moment. <br>RESULTS: By using Agilent microarray chips, we have profiled gene expression signatures in whole blood of 28 COPD patients hospitalized with distinct degree of respiratory compromise.12 of them needed of admission to the ICU, while 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparison of transcript levels between ICU and non ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to select, annotate and visualize genes by function and pathway (gene ontology). T-test evidenced 1501 genes differentially expressed between ICU and non ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients showed increased levels of neutrohil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This ?neutrophil signature? was paralleled by necessity of advanced respiratory and vital support, and presence of bacterial infection.<br>CONCLUSION: study of transcriptomic signatures in blood suggests a central role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement / modulation of the expression of these genes could represent an option for clinical monitoring and treatment of severe COPD exacerbations. <br><br>Keywords: COPD, critical, expression, gene, microarray, neutrophil, proteases.<br><br>
Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness. 273 subjects were ascertained for this analysis. This included 88 patients with non-infectious illness, 115 with viral acute respiratory infection, and 70 with bacterial acute respiratory infection. Samples were obtained at the time of enrollment, which was at initial clinical presentation. Total RNA was extracted from human blood using the PAXgene Blood RNA Kit. Microarray data were generated using the GeneChip Human Genome U133A 2.0 Array. Microarrays were generated in two microarray batches with seven overlapping samples giving rise to 280 total microarray experiments.
Project description:A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach. Patients with respiratory tract infection along with ill, non-infected controls were enrolled through the emergency department or undergraduate student health services. Whole blood was obtained to generate gene expression profiles. These profiles were then used to generate signatures of bacterial acute respiratory infection, viral acute respiratory infection, and non-infectious illness.