Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CDNA microarray data after influenza A virus infection in mouse lung tissue

ABSTRACT: The defense mechanisms that are provided by the innate immune system are a formidable barrier to influenza virus and a special immune system exists at distinct respiratory epithelium to combat invasion by influenza virus. Innate immune mechanisms for antiviral resistance are mediated by an increase of interferons’ secretion and type I and III IFNs represent the prototypical resistance mechanism as they induce diverse of Interferon stimulated genes that serve as effectors to limit viral replication. To evaluate the change of gene expressions after IAV infection, we performed gene expression analysis using the Illumina MouseWG-6 v2 Expression BeadChip (Illumina, Inc., San Diego, CA)made by Affimetrix, which comprised of more than 770,000 unique 25-mer oligonucleotide features constituting more than 28,000 genes, and each gene is represented on the array by 45,281 probes. The data were processed using the robust multi-array analysis algorithm, which performs a background correction, a normalization step, and a probe-level summary.

ORGANISM(S): Mus musculus

SUBMITTER: Hyun Jik Kim

PROVIDER: E-GEOD-70646 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

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.

Project description:Background: The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non-human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-inflammatory host responses; however, whether similar or different cellular pathways were impacted by pH1N1 virus across independent infection models remains to be further defined. To address this, we have performed a comparative transcriptomic analysis of acute host responses to a single pH1N1 influenza virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine. Results: Despite similarities in the clinical course, we observed differences in inflammatory molecules elicited, and the kinetics of their gene expression changes across all three species. The retinoid X receptor (RXR) signaling pathway controlling pro-inflammatory and metabolic processes was differentially regulated during infection in each species, though the heterodimeric RXR partner, pathway associated signaling molecules, and gene expression patterns differed in each species. Conclusions: By comparing transcriptional changes in the context of clinical and virological measures, we identified differences in the host transcriptional response to pH1N1 virus across independent models of acute infection. Antiviral resistance and the emergence of new influenza viruses have placed more focus on developing drugs that target the immune system. Underlying overt clinical disease are molecular events that suggest therapeutic targets identified in one host may not be appropriate in another. The goal of this experiment was to use global gene expression profiling to understand mouse lung cellular responses to pandemic H1N1 influenza A/Californica/04/2009 virus infection. Six-to-eight-week-old female BALB/c mice were anesthetized and inoculated with either 50 Î¼l of phosphate-buffered saline (PBS; Mock) or with 10^6 pfu of pandemic H1N1 influenza A/California/04/2009 virus in a 50 Î¼l volume, and whole lungs were collected at days 1, 3 and 5 post-inoculation. Lung samples from 9 animals for the infection group were used for array analysis, three animals per time point. Lung samples from 8 animals for the mock group were used for array analysis, three animals for the day 1 and 3 time points and 2 animals for the day 5 time point.

Project description:Classical antiviral therapy inhibit viral proteins and are subject to resistance. To counteract this emergence, alternative strategy has been developed that target cellular factors. We hypothesized that such approach could also be useful to identify broad antivirals. Influenza A virus was used as a model for viral diversity and need for therapy against unpredictable viruses as recently underlined by the H1N1 pandemic. We proposed to identify a gene-expression signature associated with infection with different influenza A virus subtypes which could help to identify potential antiviral drugs with broad spectrum. Cellular gene expression response to infection with five different human and avian influenza viruses strains was analyzed and 300 genes were determined as differentially expressed between infected and non-infected samples. Strikingly, only a few genes were induced by infection and related to immune response. A more concise list was used to screen connectivity map, a database of drug-associated gene expression profiles, for molecules with inverse profiles than the signature of infection. We hypothesized that such compounds would induce an unfavorable cellular environment for influenza virus replication. Eight potential antivirals including ribavirin were identified, and six inhibited influenza viral growth in vitro. The new pandemic H1N1 virus, which was not used to define the gene expression signature of infection, was inhibited by five of the eight identified molecules, demonstrating that this strategy could help to identify broad spectrum antivirals. This is the first study showing that a gene expression based-screening can be used to identify antivirals. Such approaches could accelerate the drug discovery progress and could be extended to other pathogens. A549 (human lung epithelial cells) were infected with 5 different influenza A strains (A/New Caledonia/20/99 (H1N1), A/Moscow/10/99 (H3N2), A/Lyon/969/09 (H1N1 SOI-V), A/Turkey/582/2006 (H5N1), A/Finch/England/2051/94 (H5N2), and A/Chicken/Italy/2076/99 (H7N1)) or mock infected. Five independant replicates were done and hybridized on a different microarray. The overall design is thus composed of 5 mock samples, and 5x5 infected samples.

Dataset Information

CDNA microarray data after influenza A virus infection in mouse lung tissue

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets