Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA355641 | ENA |
REPOSITORIES: ENA
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Project description:Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty one volunteers participated in an influenza challenge trial. We calculated the Daily Sum of Scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 hours post challenge was profiled on Illumina HT12v4 microarrays. We selected 19 genes with the largest fold change to train a random forest model with out of bag sampling cross validation. We observed good concordance between predicted and actual scores in an independent test set (overall Pearson correlation, r = 0.57; RMSE = -16.1%).
2017-06-10 | GSE90732 | GEO
Project description:The biological basis for the increased severity of influenza A viruses during the 2009 influenza pandemic remains unclear. Intra-host evolution of quasispecies and strong inflammation were identified as important hallmarks of severe pandemic H1N1 influenza A virus 2009 (A(H1N1)pdm09) infection. HA-222D/G quasispecies of A(H1N1)pdm09 were shown to undergo fast evolution and to cause severe influenza in human and mice. Here, we analysed the whole genome transcriptional response of mice infected with the A/Jena/5258/09 (mpJena/5258) virus over a period of 12 days to gain insights into the pathogenesis of A(H1N1)pdm09 HA-222D/G quasispecies on a molecular level. Remarkably, the transcriptional response to severe mpJena/5258 showed biphasic expression profile for the majority of genes which was never shown before. The gene expression analysis shows first peak with 968 differentially expressed genes at day 2 post infection (p.i.), followed by a stagnant recovery phase with 359 differentially expressed genes at day 4 p.i., and a second peak with 1001 differentially expressed genes at day 7 p.i., finally followed by a recovery phase. Using a reverse engineering strategy, a regulatory network was inferred to identify key interactions leading to severe pathogenesis of mpJena/5258. Known regulatory interactions were extracted by Pathway Studio 9.0 and softly integrated during network inference. The results demonstrate a hyper-responsive action and a positive feedback loop of IFN gamma (Ifng), Stat1 and Tlr3 signalling during mpJena/5258 infection. In conclusion, mpJena/5258 infection is associated with biphasic gene expression profile and a positive feedback mechanism of Ifng which correlates with the evolution of HA-222D/G quasispecies and leads to overwhelming immune response. A significant correlation were found between the co-expression action of three genes (Ifng, Stat1 and Tlr3) with a phenomenological clinical symptom score.
2017-02-10 | GSE67241 | GEO
Project description:Pandemic influenza H1N1 (pdmH1N1) virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses, suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However, a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus.
2010-10-06 | GSE24533 | 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
2010-03-31 | GSE17079 | GEO
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.
2014-01-23 | GSE54293 | GEO
Project description:Despite increases in vaccination coverage, reductions in influenza-related mortality have not been observed. Better vaccines are therefore required and influenza challenge studies can be used to test the efficacy of new vaccines. However, this requires the accurate post-challenge classification of subjects by outcome, which is limited in current methods that use artificial thresholds to assign “symptomatic” and “asymptomatic” phenotypes. We present data from an influenza challenge study in which 22 healthy adults (11 vaccinated) were inoculated with H3N2 influenza (A/Wisconsin/67/2005). We generated genome-wide gene expression data from peripheral blood taken immediately before the challenge and at 12, 24, and 48 hours post-challenge. Variation in symptomatic scoring was found among those with laboratory confirmed influenza. By combining the dynamic transcriptomic data with the clinical parameters this variability can be reduced. We identified four subjects with severe laboratory confirmed flu that show differential gene expression in 1,103 probes 48 hours post-challenge compared to the remaining subjects. We have further reduced this profile to 6 genes that can be used to define these subjects. We have used this gene set to predict symptomatic infection from an independent study. This analysis gives further insight into host-pathogen interactions during influenza infection. However, the major potential value is in the clinical trial setting by providing a more quantitative method to better classify symptomatic individuals post influenza challenge. Twenty two healthy volunteers were enrolled for an influenza challenge study. Eleven were vaccinated thirty days before challenge with H3N2 influenza. Whole blood was collected in PAXgene tubes prior to influenza challenge and then at three further timepoints (12, 24 and 48 hours post-challenge).
2014-11-06 | E-GEOD-61754 | 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 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:This SuperSeries is composed of the following subset Series: GSE36461: MiRNA profiling during infection with H1N1 influenza A virus (A/Mexico/InDRE4487/H1N1/2009) GSE36462: MiRNA profiling during infection with H7N7 influenza A virus (A/Ck/Germany/R28/H7N7/2003) GSE36553: mRNA profiling during infection with H1N1 influenza A virus (A/Mexico/InDRE4487/H1N1/2009) Refer to individual Series
2012-04-09 | E-GEOD-36555 | biostudies-arrayexpress
Project description:A comparative gene expression analysis was performed using cDNA microarray technology in passage-2 normal human nasal epithelial cells to identify the differentially expressed genes between influenza A virus infected and uninfected cells. Two samples were analyzed. RNA was extracted from normal human nasal epithelial cells, which were further divided as H1N1 PI 0 day and H1N1 PI 2 day (influenza A virus infection for 48 hr).
2013-05-02 | E-GEOD-46567 | biostudies-arrayexpress