Project description:We used the microarray data to analyze host cells response on mouse macrophage cells infected with HRSV The HRSV infected mouse macrophage cells were harvested at 4 and 24 hpi and RNA extraction was performed using standard protocol as described by Affymetrix. The aim of this experiment is to analyze host cell response to HRSV infection.
Project description:Human respiratory syncytial virus (hRSV) is a major cause of morbidity and mortality in the pediatric, elderly, and immune compromised populations. A gap in our understanding of hRSVdisease pathology is the interplay between virally encoded immune antagonists and host components that limit hRSV replication. hRSV encodes for non-structural (NS) proteins that are important immune antagonists; however, the role of these proteins in viral pathogenesis is incompletely understood. Here we report the crystal structure of hRSV NS1 protein, which suggests that NS1 is a structural paralog of hRSV matrix (M) protein. Comparative analysis of the shared structural fold with M revealed regions unique to NS1. Studies on NS1 WT or mutant alone or in recombinant RSVs demonstrate that structural regions unique to NS1 contribute to modulation of host responses, including inhibition of type I IFN responses, suppression of dendritic cell maturation, and promotion of inflammatory responses. Transcriptional profiles of A549 cells infected with recombinant RSVs show significant differences in multiple host pathways, suggesting that NS1 may have a greater role in regulating host responses than previously appreciated. These results provide a framework to target NS1 for therapeutic development to limit hRSV associated morbidity and mortality.
Project description:Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, but other viruses such as rhinovirus also occur and are clinically indistinguishable. In hospitalized infants with bronchiolitis, the analysis of the peripheral blood mononuclear cells (PBMC) gene expression might be useful for identification the etiologies caused by HRSV and human rhinovirus (HRV) and to the development of future tests, as well as to elucidate the pathogenic mechanisms triggered by different viral agents and new therapeutic possibilities. In this study, we conducted a comparative global gene expression analysis of infants with acute viral bronchiolitis infected by HRSV (HRSV group) or HRV (HRV group).
Project description:The respiratory epithelium is a polarised layer at the interface between the outside environment and deeper lung structures, overlaid by the epithelial lining fluid (ELF). This provides a mechanical and immunological barrier to inhaled particulates, such as viruses. Human respiratory syncytial virus (hRSV) is a major cause of disease in humans, and targets the respiratory epithelium. However, little is known of the disruption of the ELF proteome in the context of virus-driven respiratory illnesses. To address this, a proteomics approach was combined with an ex-vivo human airway epithelial model (HAE) to investigate the apical and basolateral secretome in hRSV-infected cultures. This demonstrated that several apically- and basolaterally-restricted proteins were subsequently secreted in both directions upon infection, while a number of proteins saw their apical/basolateral abundance ratios significantly altered. Furthermore, another 35 proteins were uniquely identified after hRSV treatment. Importantly, some of these changes were correlated in nasal aspirates (NA) from children with and without hRSV. This study showed that hRSV could affect airway secretions, and disrupted the directionality of the respiratory epithelium.
Project description:Using microarray technology, we compared the global expression pattern of uterine RNA from ovariectomized control mice to those of ovariectomized mice treated with estradiol for various intervals between 30 minutes and 24 hours. Keywords: estrogen, uterus, genomic, mouse
Project description:Human monocyte-derived macrophage cells were infected with Chikungunya virus (CHIKV) to identify and quantify intracellular transcriptional changes that contribute to the host response to infection with CHIKV. RNA was collected from these cells at 8 and 24 hours post-infection (hpi) and were compared to mock-infected cells. The RNAseq data was then analyzed to determine the genes, functions, and signaling pathways that were significantly affected in an effort to predict existing drugs that could be repurposed as potential therapeutics for CHIKV.