Project description:Transcriptional responses in lungs of mice infected with Respiratory Syncytial Virus (RSV) were compared to a control and mock infections
Project description:In this study we investigated whether there exists a genomic signature that can accurately predict the course of a respiratory syncytial virus (RSV) infection in hospitalized young infants. We used early blood microarray transcriptome profiles from 39 infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease.
Project description:The clinical phenotype of infants infected with respiratory syncytial virus (RSV) differs from that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RSV is the leading cause of hospitalization for lower respiratory tract infection and carries a significant higher risk of respiratory failure compared to SARS-CoV-2, which has been generally linked to fever and croup in young infants. The underlying mechanisms these differences remain unclear. We analyzed peripheral blood mononuclear cells (PBMCs) and serum from infants infected with SARS-CoV-2 (n=30), RSV (n=19), and healthy controls (n=17) using single-cell RNA sequencing, single-nucleus ATAC sequencing and cytokine profiling. Both viruses triggered type I interferon responses across PBMC subsets but differed in their NK cell and inflammatory responses. Severe RSV cases were characterized by lower NK cell percentages, lower IFNG expression and diminished chromatin accessibility at T-BET and EOMES binding sites in NK cells. Furthermore, RSV infections were associated with increased frequencies of CD4+ TEMRA and memory Treg cells. In contrast, SARS-CoV-2 infections were marked by more pronounced pro-inflammatory signatures, including increased transcriptional and epigenetic activity at NFKB factors and higher serum TNF concentrations. These findings highlight distinct immune response pathways in RSV and SARS-CoV-2 infections that may inform future therapeutic strategies.
Project description:The clinical phenotype of infants infected with respiratory syncytial virus (RSV) differs from that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RSV is the leading cause of hospitalization for lower respiratory tract infection and carries a significant higher risk of respiratory failure compared to SARS-CoV-2, which has been generally linked to fever and croup in young infants. The underlying mechanisms these differences remain unclear. We analyzed peripheral blood mononuclear cells (PBMCs) and serum from infants infected with SARS-CoV-2 (n=30), RSV (n=19), and healthy controls (n=17) using single-cell RNA sequencing, single-nucleus ATAC sequencing and cytokine profiling. Both viruses triggered type I interferon responses across PBMC subsets but differed in their NK cell and inflammatory responses. Severe RSV cases were characterized by lower NK cell percentages, lower IFNG expression and diminished chromatin accessibility at T-BET and EOMES binding sites in NK cells. Furthermore, RSV infections were associated with increased frequencies of CD4+ TEMRA and memory Treg cells. In contrast, SARS-CoV-2 infections were marked by more pronounced pro-inflammatory signatures, including increased transcriptional and epigenetic activity at NFKB factors and higher serum TNF concentrations. These findings highlight distinct immune response pathways in RSV and SARS-CoV-2 infections that may inform future therapeutic strategies.
Project description:Bovine respiratory epithelial cells have different susceptibility to bovine
respiratory syncytial virus infection. The cells derived from the lower
respiratory tract were significantly more susceptible to the virus than those
derived from the upper respiratory tract. Pre-infection with virus of lower
respiratory tract with increased adherence of P. multocida; this was not the
case for upper tract. However, the molecular mechanisms of enhanced
bacterial adherence are not completely understood. To investigate whether
virus infection regulates the cellular adherence receptor on bovine trachea-,
bronchus- and lung-epithelial cells, we performed proteomic analyses.
Project description:mRNA expression data from BALB/c mice which were infected intranasally with Respiratory Syncytial Virus (or Hep-2 cell lysate control) at 1 week old and challenged with PBS or house dust mite (HDM) extract as adults. Experimental groups: RH – neonatal RSV, adult HDM, RP – neonatal RSV, adult PBS, HH – neonatal Hep-2, adult HDM and HP – neonatal Hep-2, adult PBS.
Project description:Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), while ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
Project description:Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), while ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
Project description:Respiratory syncytial virus (RSV) is a seasonal respiratory pathogen that primarily affects young children, potentially causing severe lower respiratory tract disease. Despite the high disease burden, understanding of RSV pathophysiology remains limited. To address this, advanced RSV infection models are needed. While HEp-2 cells are widely used due to their high susceptibility to RSV, they do not accurately reflect the host response of the human respiratory tract. In this study, we evaluated human induced pluripotent stem cell-derived respiratory organoids, which contain respiratory epithelial cells, immune cells, fibroblasts, and vascular endothelial cells, for their potential to model RSV infection and support pharmaceutical research. RSV-infected organoids exhibited high viral genome and protein expression, epithelial layer destruction, and increased collagen accumulation. Pro-inflammatory cytokine levels in culture supernatants also increased post-infection. Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), while ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research.
Project description:The objective of this study was to better understand the immune response to RSV at the port of entry, in the upper respiratory tract mucosa of children naturally infected with RSV.