Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA263363 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:NS1 proteins from avian influenza viruses like the 1918 pandemic NS1 are capable of inhibiting the key signaling integrator c-Abl (Abl1), resulting in massive cytopathic cell alterations. In the current study, we addressed the consequences of NS1-mediated alteration of c-Abl on acute lung injury and pathogenicity. Comparing isogenic strains that differ only in their ability to inhibit c-Abl, we observed elevated pathogenicity for the c-Abl-inhibiting virus. NS1-mediated block of c-Abl resulted in severe lung pathology and massive edema formation and facilitated secondary bacterial pneumonia. This phenotype was independent of differences in replication and immune responses, defining it as an NS1 virulence mechanism distinct from its canonical functions. Microarray analysis revealed extensive down-regulation of genes involved in cell integrity and vascular endothelial regulation. In conclusion, NS1 protein-mediated blockade of c-Abl signaling drives acute lung injury and primes for bacterial co-infections revealing potential insights into the pathogenicity of the 1918 pandemic virus. Lung transcription analysis of Influenza A virus infected mice.
2014-11-03 | E-GEOD-62169 | biostudies-arrayexpress
Project description:NS1 proteins from avian influenza viruses like the 1918 pandemic NS1 are capable of inhibiting the key signaling integrator c-Abl (Abl1), resulting in massive cytopathic cell alterations. In the current study, we addressed the consequences of NS1-mediated alteration of c-Abl on acute lung injury and pathogenicity. Comparing isogenic strains that differ only in their ability to inhibit c-Abl, we observed elevated pathogenicity for the c-Abl-inhibiting virus. NS1-mediated block of c-Abl resulted in severe lung pathology and massive edema formation and facilitated secondary bacterial pneumonia. This phenotype was independent of differences in replication and immune responses, defining it as an NS1 virulence mechanism distinct from its canonical functions. Microarray analysis revealed extensive down-regulation of genes involved in cell integrity and vascular endothelial regulation. In conclusion, NS1 protein-mediated blockade of c-Abl signaling drives acute lung injury and primes for bacterial co-infections revealing potential insights into the pathogenicity of the 1918 pandemic virus.
2014-11-03 | GSE62169 | GEO
Project description:To study the effects of secondary bacterial infection during 1918 pandemic H1N1 influenza virus infection, BALB/c mice were inoculated with the fully reconstructed 1918 influenza virus followed by inoculation with pneumococcus 72h later. To study the effects of secondary bacterial infection during 1918 pandemic H1N1 influenza virus infection, BALB/c mice were inoculated with the fully reconstructed 1918 influenza virus followed by inoculation with pneumococcus 72h later.
2015-09-20 | E-GEOD-70445 | biostudies-arrayexpress
Project description:To study the effects of secondary bacterial infection during 1918 pandemic H1N1 influenza virus infection, BALB/c mice were inoculated with the fully reconstructed 1918 influenza virus followed by inoculation with pneumococcus 72h later.
2015-09-20 | GSE70445 | GEO
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).
2013-07-16 | GSE48890 | GEO
Project description:The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. A reconstructed version of the 1918 (H1N1) virus has been shown to also highly pathogenic in mice; however, the potential virulence and pathogenicity of the 1918 virus in nonhuman primates in unknown. In these studies, we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. To characterize the global gene expression host response, oligonulceotide microarray analysis was performed on RNA isolated from the bronchus of macaques infected with either the 1918 virus or a humanized contemporary H1N1 influenza virus (A/Kawasaki/173/01). These experiments showed that infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, suggesting that atypical host innate immune responses may contribute to lethality.
2007-01-18 | E-TABM-181 | biostudies-arrayexpress
Project description:Background: Pandemic H1N1 influenza A is a newly emerging strain of human influenza that is easily transmitted between people and has spread globally to over 116 countries. Human infection leads to symptoms ranging from mild to severe with lower respiratory complications observed in a small but significant number of infected individuals. Little is currently known about host immunity and Pandemic H1N1 influenza infections. Methods: We examined the pathogenic potential of the pandemic influenza A vaccine strain, A/California/07/2009 (H1N1), in ferrets, and characterized the host immune responses using microarray analysis. Gene expression profiles in lung tissue were compared with those from ferrets infected with A/Brisbane/59/2007. Results: Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of ISGs were expressed early, correlated to lung pathology, and abruptly decreased expression in 5 days. Interestingly, the drop in innate immune gene expression was replaced by a significant increase in the expression of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-pandemic influenza H1N1 antibodies were also observed on day 7, commensurate with the elimination of viral load. Conclusions: We propose that the innate phase of host immunity causes lung pathology and a delay or failure to effectively switch to the adaptive phase contributes to morbidity and mortality during severe human pandemic H1N1 influenza A infections. Keywords: influenza, immune response, cytokines, chemokines, lung infection, time course
2010-03-31 | GSE17079 | GEO
Project description:The “Spanish influenza” of 1918 claimed an unprecedented number of lives, yet the determinants of virulence for this virus are still not fully understood. Here, we used functional genomics and an in vitro human lung epithelial cell infection model to define the global host transcriptional response to the eight-gene 1918 virus. To better understand the role of the 1918 virus NS1 gene, we also evaluated the host response to fully reconstructed 1918 and reassortant 1918 virus containing the NS1 gene from A/Texas/36/91 (a seasonal isolate of human influenza virus).
2012-05-14 | GSE37951 | GEO
Project description:Background: Pandemic H1N1 influenza A is a newly emerging strain of human influenza that is easily transmitted between people and has spread globally to over 116 countries. Human infection leads to symptoms ranging from mild to severe with lower respiratory complications observed in a small but significant number of infected individuals. Little is currently known about host immunity and Pandemic H1N1 influenza infections. Methods: We examined the pathogenic potential of the pandemic influenza A vaccine strain, A/California/07/2009 (H1N1), in ferrets, and characterized the host immune responses using microarray analysis. Gene expression profiles in lung tissue were compared with those from ferrets infected with A/Brisbane/59/2007. Results: Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of ISGs were expressed early, correlated to lung pathology, and abruptly decreased expression in 5 days. Interestingly, the drop in innate immune gene expression was replaced by a significant increase in the expression of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-pandemic influenza H1N1 antibodies were also observed on day 7, commensurate with the elimination of viral load. Conclusions: We propose that the innate phase of host immunity causes lung pathology and a delay or failure to effectively switch to the adaptive phase contributes to morbidity and mortality during severe human pandemic H1N1 influenza A infections. Keywords: influenza, immune response, cytokines, chemokines, lung infection, time course In the experiment with influenza A/California/07/2009 (H1N1),15 ferrets were randomly allocated to 5 groups: Day 0 (before infection), and Day 3, 5, 7 and 14 (post infection) with 3 biological replicates for each group. Likewise, a second experiment with A/Brisbane/59/2007 (H1N1) was carried out using the same experimental groups, except for a group in Day 2, instead Day 3. Ferrets were euthanized and lung tissue was excised for RNA purification on the scheduled date. The subsequent gene expression analysis was performed with Affymetrix GeneChip Canine Genome 2.0 Array. Day 0 groups were used as control.
2010-04-12 | E-GEOD-17079 | biostudies-arrayexpress
Project description:The purpose of this experiment was to understand the pathogenic role of individual 1918 genes on the host response to the 1918 pandemic influenza virus. We examined reassortant avian viruses nearly identical to the pandemic 1918 virus (1918-like avian virus) carrying either the 1918 HA or PB2 gene. Both genes enhanced 1918-like avian virus replication, but only the mammalian host adaptation of the 1918-like avian virus through reassortment of the 1918 PB2 led to increased lethality in mice. We demonstrate that 1918 PB2 enhances immune and inflammatory responses concomitant with increased cellular infiltration in the lung. We also show that 1918 PB2 expression results in the repression of both canonical and non-canonical Wnt signaling pathways which are crucial for inflammation mediated lung regeneration and repair.
2015-12-31 | GSE70502 | GEO