Akt inhibitor MK2206 prevents influenza A(H1N1)pdm09 virus infection in vitro
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54293 | GEO | 2014/01/23
SECONDARY ACCESSION(S): PRJNA236108
REPOSITORIES: GEO
Similar Datasets
Project description:The influenza A(H1N1)pdm09 virus caused a global flu pandemic in 2009 and contributes to seasonal epidemics. Different treatment and prevention options for influenza have been developed and applied with limited success. Here we report that an Akt inhibitor MK2206 possesses potent antiviral activity against influenza A(H1N1)pdm09 virus in vitro. We showed that MK2206 blocks the entry of different A(H1N1)pdm09 strains into cells. Moreover, MK2206 prevented A(H1N1)pdm09-mediated activation of cellular signaling pathways and the development of cellular immune responses. Importantly, A(H1N1)pdm09 virus was unable to develop resistance to MK2206. Thus, MK2206 is a potent anti-influenza A(H1N1)pdm09 agent. Total RNA obtained from NCI-H1666 cells, which are non-small cell lung cancer cell line. NCI-H1666 cells were non- or MK2206-treated (10 μM) and mock- or virus-infected (A/Helsinki/p14/2009) at moi of 3.
2014-01-23 | E-GEOD-54293 | biostudies-arrayexpress
Project description:To further understand the molecular pathogenesis of the 2009 pandemic H1N1 influenza virus infection, we profiled cellular miRNAs of lung tissue from BALB/c mice infected with influenza virus BJ501 and a mouse-adapted influenza virus A/Puerto Rico/8/34 (H1N1)(PR8) as a comparison.
2013-04-17 | GSE46087 | GEO
Project description:Annually, influenza A viruses circulate the world causing wide-spread sickness, economic loss, and death. One way to better defend against influenza virus-induced disease may be to develop novel host-based therapies, targeted at mitigating viral pathogenesis through the management of virus-dysregulated host functions. However, mechanisms that govern aberrant host responses to influenza virus infection remain incompletely understood. We previously showed that the pandemic H1N1 virus influenza A/California/04/2009 (H1N1; CA04) has enhanced pathogenicity in the lungs of cynomolgus macaques relative to a seasonal influenza virus isolate (A/Kawasaki/UTK-4/2009 (H1N1; KUTK4)). Here, we used microarrays to identify host gene sequences that were highly differentially expressed (DE) in CA04-infected macaque lungs, and we employed a novel strategy – combining functional and pathway enrichment analyses, transcription factor binding site enrichment analysis and protein-protein interaction data – to create a CA04 differentially regulated host response network. This network describes enhanced viral RNA sensing, immune cell signaling and cell cycle arrest in CA04-infected lungs, and highlights a novel, putative role for the MYC-associated zinc finger (MAZ) transcription factor in regulating these processes.
2012-10-01 | GSE39018 | GEO
Project description:Fribourg2014 - Dynamics of viral antagonism and innate immune response (H1N1 influenza A virus - NC/99)
The dynamics of the interplay between the viral antagonism and the innate immune response has been studied using modelling approaches. The responses of human monocyte-derived dendritic cells infected by two influenza A H1N1 strains (the pandemic swine-origin A/California/4/2009 (Cal/09) and the seasonal A/New Caledonia/20/1999 (NC/99)) that have different clinical outcomes have been modelled. From the time course gene expression measurements of a set of selected genes, the dynamic features of viral antagonism and innate immune response are extracted. It is found that the strength and the time scale of action of viral antagonism is significantly different between the two viruses. This model describes the viral infection by seasonal NC/99.
This model is described in the article:
Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response.
Fribourg M, Hartmann B, Schmolke M, Marjanovic N, Albrecht RA, García-Sastre A, Sealfon SC, Jayaprakash C, Hayot F.
J Theor Biol. 2014 Mar 2;351C:47-57.
Abstract:
Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.
This model is hosted on BioModels Database and identified
by: MODEL1403310001.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication for more information.
2024-09-02 | BIOMD0000000529 | BioModels
Project description:Fribourg2014 - Dynamics of viral antagonism and innate immune response (H1N1 influenza A virus - Cal/09)
The dynamics of the interplay between the viral antagonism and the innate immune response has been studied using modelling approaches. The responses of human monocyte-derived dendritic cells infected by two influenza A H1N1 strains (the pandemic swine-origin A/California/4/2009 (Cal/09) and the seasonal A/New Caledonia/20/1999 (NC/99)) that have different clinical outcomes have been modelled. From the time course gene expression measurements of a set of selected genes, the dynamic features of viral antagonism and innate immune response are extracted. It is found that the strength and the time scale of action of viral antagonism is significantly different between the two viruses. This model describes the viral infection by seasonal Cal/09.
This model is described in the article:
Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response.
Fribourg M, Hartmann B, Schmolke M, Marjanovic N, Albrecht RA, García-Sastre A, Sealfon SC, Jayaprakash C, Hayot F.
J Theor Biol. 2014 Mar 2;351C:47-57.
Abstract:
Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.
This model is hosted on BioModels Database and identified
by: MODEL1403310002.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication for more information.
2024-09-02 | BIOMD0000000528 | BioModels
Project description:This study used virological, histological, immunological and global gene expression to compare the virlence of two newly emerged 2009 H1N1 isolates (A/Mexico/InDRE4487/2009 and A/Mexico/4108/2009) and current seasonal H1N1 influenza strain (A/Kawasaki/UTK-4/2009) in experimentally infected cynomolgus macaques. We showed that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia. Disease associated with these SOIV isolates was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Total dose of 7 x 10^6 pfu of influenza virus by a combination of different routes: intratracheal (4 ml), intranasal (0.5 ml each nostril), intraocular (0.5 ml each eye), and oral (1 ml).
2011-08-29 | E-GEOD-31694 | biostudies-arrayexpress
Project description:Differential expression was determined in Calu-3 cells between mock infected and infected with H1N1 influenza virus A/Netherlands/602/2009 at nine time points post-infection. As a comparison, cells were also infected with A/CA/04/2009 H1N1 influenza virus at 4 time points post-infection.
2012-09-13 | GSE40844 | GEO
Project description:Annually, influenza A viruses circulate the world causing wide-spread sickness, economic loss, and death. One way to better defend against influenza virus-induced disease may be to develop novel host-based therapies, targeted at mitigating viral pathogenesis through the management of virus-dysregulated host functions. However, mechanisms that govern aberrant host responses to influenza virus infection remain incompletely understood. We previously showed that the pandemic H1N1 virus influenza A/California/04/2009 (H1N1; CA04) has enhanced pathogenicity in the lungs of cynomolgus macaques relative to a seasonal influenza virus isolate (A/Kawasaki/UTK-4/2009 (H1N1; KUTK4)). Here, we used microarrays to identify host gene sequences that were highly differentially expressed (DE) in CA04-infected macaque lungs, and we employed a novel strategy M-bM-^@M-^S combining functional and pathway enrichment analyses, transcription factor binding site enrichment analysis and protein-protein interaction data M-bM-^@M-^S to create a CA04 differentially regulated host response network. This network describes enhanced viral RNA sensing, immune cell signaling and cell cycle arrest in CA04-infected lungs, and highlights a novel, putative role for the MYC-associated zinc finger (MAZ) transcription factor in regulating these processes. Lung tissues used for microarray studies were obtained from 13 female cynomolgus macaques infected with influenza viruses. 6 animals were inoculated with influenza A/California/04/2009 and 6 animals were inoculated with influenza A/Kawasaki/UTK-4/2009. 1 uninfected animal served as a negative control. On days 3 and 7 post-infection (p.i.), lung tissues were harvested from the middle and lower lung lobes of 3animals in each infection group (N = 26 total samples were collected, 3 samples were removed from the study due to low RNA quality). All but 3 samples were collected from visually apparent virus-induced gross lesions. Two lung tissue samples were obtained from middle and lower lobes of the uninfected animal at the start of the experiment.
2012-10-01 | E-GEOD-39018 | biostudies-arrayexpress
Project description:Infection with pandemic A/H1N1 influenza virus induces high levels of circulating and lung pro-inflammatory cytokines and chemokines in experimental models and humans. These inflammatory mediators contribute to poor clinical outcomes of this infection. To compare the regulation of inflammatory responses in seasonal versus pandemic influenza A virus infections, we analyzed the expression of mRNA by the human gene st 1.0 array (affymetrix). We identifed a number of differentially expressed genes by infection of the A/H1N1 compared to the seasonal virus. Gene ontology analysis of these genes found that most of them are involved in several aspects of immunity. These studies suggest that factors inherent in the pandemic A/H1N1 viral strain may augment the production of inflammatory mediators by inhibiting SOCS- 1 expression and that infection with this viral strain also modifies the expression of several immunity related genes and pathways . The experimental design consist in 1 pool and its replicate containing 5 independent experiments from treated macrophages with Influenza A/H1N1 virus, and 1 more pool and its replicate containing 5 independent experiments from treated macrophages with seasonal influenza A virus. By this way, the total number of the samples analyzed was 10 in 4 microarrays.
2012-06-09 | E-GEOD-36012 | biostudies-arrayexpress