Project description:The pathogenesis of avian influenza A H5N1 virus in human has not been clearly elucidated. There have been increasing evidence suggesting a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. However, the role of aberrant innate immune response in human lungs infected by avian influenza H5N1 virus has not been explored and direct evidence for inappropriate innate responses in lungs of avian influenza H5N1 virus infected patients is lacking.
Project description:The pathogenesis of avian influenza A H5N1 virus in human has not been clearly elucidated. There have been increasing evidence suggesting a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. However, the role of aberrant innate immune response in human lungs infected by avian influenza H5N1 virus has not been explored and direct evidence for inappropriate innate responses in lungs of avian influenza H5N1 virus infected patients is lacking. In order to obtain evidences for the proposed role of aberrant innate immune response in avian influenza H5N1 virus pathogenesis in human, we analyzed expression profile of lung tissues from two fatal cases of avian influenza H5N1 virus infected patients in comparison to normal human lung using an expression microarray.
Project description:To study miRNA expression profiles during highly pathogenic avian influenza virus infection, we conducted global miRNA expression profiling in human lung epithelial cells (A549) with or without H5N1 IAV infection. .
Project description:Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses and the current H1N1 pandemic highlight the need for a more detailed understanding of influenza virus pathogenesis. To investigate the host transcriptional response induced by pathogenic influenza viruses, we used a functional-genomics approach to compare gene expression profiles in lungs from wild-type 129S6/SvEv and interferon receptor (IFNR) knockout mice infected with either the fully reconstructed H1N1 1918 pandemic virus (1918) or the highly pathogenic avian H5N1 virus Vietnam/1203/04 (VN/1203).
Project description:Transcriptional profiling was carried out on lung and ileum samples at 1dpi and 3dpi from chickens infected with either low pathogenic (H5N2) or highly pathogenic (H5N1) avian influenza. Infected birds were compared to control birds at each time point.
Project description:Transcriptional profiling was carried out on lung and ileum samples at 1dpi and 3dpi from ducks infected with either low pathogenic (H5N2) or highly pathogenic (H5N1) avian influenza. Infected birds were compared to control birds at each time point.
Project description:Transcriptional profiling was carried out on lung and ileum samples at 1dpi and 3dpi from quail infected with either low pathogenic (H5N2) or highly pathogenic (H5N1) avian influenza. Infected birds were compared to control birds at each time point.
Project description:Over the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, and yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a systems biology method called weighted gene correlation network analysis (WGCNA) to identify and statistically validate signaling sub-networks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). A detailed examination of two sub-networks involved in the immune response and keratin filament formation revealed potential novel mediators of HPAI H5N1 pathogenesis, and additional experiments validated upregulation of these transcripts in response to VN1203 infection in C57BL/6 mice. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection, and identify novel avenues for perturbation studies and potential therapeutic intervention of fatal HPAI H5N1 disease.
Project description:Viral pneumonia has been frequently reported during early stages of influenza virus pandemics and in many human cases of highly pathogenic avian influenza (HPAI) H5N1 virus infection. To better understand the pathogenesis of this disease, we produced non-lethal viral pneumonia in rhesus macaques by using an HPAI H5N1 virus (A/Anhui/2/2005; referred to as Anhui/2). Infected macaques were monitored for 14 days, and tissue samples were collected at 6 time points for virologic, histopathologic and transcriptomic analyses.