Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NS1-mediated inhibition of c-Abl results in acute lung injury and priming for bacterial co-infections; insights into 1918 H1N1 pandemic

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: David Finkelstein

PROVIDER: E-GEOD-62169 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

NS1-mediated inhibition of c-Abl results in acute lung injury and priming for bacterial co-infections; insights into 1918 H1N1 pandemic

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

Acute host transcriptonal response to r1918 influenza and r1918 influenza containing the NS1 gene from A/Texas/36/91 in A549 cells

2012-05-14 | GSE37951 | GEO

Acute host transcriptonal response to A/Texas/36/91 influenza and A/Texas/36/91 influenza containing the NS1 gene from r1918 in A549 cells

2012-05-14 | GSE37829 | GEO

Acute host transcriptonal response to r1918 influenza and r1918 influenza containing the NS1 gene from A/Texas/36/91 in A549 cells

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). A549 cells were infected with either recombinant 1918 influenza, a chimeric virus that contained seven genes from recombinant 1918 and the NS1 from A/Texas/36/91 (Tx/91), or mock. Cells were harvested for microarray analysis at 2, 6, and 24hr following infection.

2012-05-13 | E-GEOD-37951 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (colony)

Project description:The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel findings that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. 3 colonies fron control and H1N1 influenza treated lungs (12 dpi) ,each were picked for whole genome microarray analysis

2011-11-01 | E-GEOD-32600 | biostudies-arrayexpress

1918 pandemic influenza virus and pneumococcus co-infection results in activation of coagulation and widespread pulmonary microvascular thrombosis in mice and humans

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

The 1918 PB2 protein, not HA, enhances the virulence of an avian influenza virus closely related to the 1918 pandemic virus through the inhibition of wnt signaling.

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

Acute lung injury results from innate sensing of viruses by an ER stress pathway

Project description:Incursions of new pathogenic viruses into humans from animal reservoirs are occurring with alarming frequency. The molecular underpinnings of immune recognition, host responses, and pathogenesis in this setting arepoorly understood. We studied pandemic influenza viruses to determine the mechanism by which increasing glycosylation during evolution of surface proteins facilitates diminished pathogenicity in adapted viruses. ER stressduring infection with poorly glycosylated pandemic strains activated the unfolded protein response, leading to inflammation, acute lung injury, and mortality. Seasonal strains or viruses engineered to mimic adapted viruses displaying excess glycans on the hemagglutinin did not cause ER stress, allowing preservation of the lungs and survival. We propose that ER stress resultingfrom recognition of non-adapted viruses is utilized to discriminate “non-self” at the level of protein-processing and to activate immune responses, with unintended consequences on pathogenesis. Understanding this mechanism should improve strategies for treating acute lung injury from zoonotic viral infections. Lung transcription analysis of Influenza A virus infected mice.

2015-07-06 | E-GEOD-65075 | biostudies-arrayexpress

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection (LCM_Four populations of cells)

Project description:The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel findings that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. H1N1 infected mice were sacrificed at 25 dpi and the lungs were snap frozen and embedded in OCT. Sections were cut and stained for several markers and consecutive sections were used for Laser Capture Microdissection.The PALMM-BM-. Robot Microbeam laser microdissection system (P.A.L.M. GmbH, Bernried, Germany) in combination with a Zeiss microscope was used to dissect out desired cells.Four population of cells were collected namely alveoli, Krt5+,Spc+ and K5&SPC-. Isolated cells were collected in adhesive caps (Carl Zeiss, Inc.) and RNA was extracted using the Pico Pure RNA extraction kit (Arcturus).

2011-11-01 | E-GEOD-32602 | biostudies-arrayexpress

Transcription profiling of bronchus from macaques infected with either the 1918 influenza virus or a humanized contemporary H1N1 influenza virus

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data