Project description:We found liraglutide ameliorates influenza virus infection in mice.Using a microarray, we identified a group of up-regulated genes that could explain influenza improvement.
Project description:Ducks and wild aquatic birds are the natural reservoirs of avian influenza viruses. However, the host proteome response that causes disease in vivo during infection by the highly pathogenic avian influenza (HPAI) H5N1 virus is still not well understood. In the present study, we compared the proteome response in Muscovy duck lung tissue during 3 day of infection with either a highly virulent or an avirulent H5N1 virus. During infection, proteins involved in immune response of neutrophils and size of cells were increased markedly in the lung by the virulent strain, while the avirulent strain evoked a distinct response, characterized by an increase in proteins involved in cell movement, maturation of dendritic cells, adhesion of phagocytes, and immune response of macrophages.
Project description:Analysis of lung samples from mice infected with a severe H5N1 influenza virus (VN/1203/04/H5N1) or a mild H1N1 influenza virus (NYMC-X-179A) on day 3 and day 5 post-infection. Uninfected controls were used for comparison.
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:Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild to moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models, however little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathology and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days post-infection. Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident following the clearance of virus and resolution of morbidity. Influenza infection induced robust changes in the lung transcriptome including a significant impact on inflammatory and extracellular matrix protein expression.
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
Project description:To identify molecular characteristics of lung tissue from db/db mice treated with DMSO or a new insulin sensitizer MSDC-0602K at day 5 post influenza virus infection, we isolated RNA from lungs with various treatments and examined by bulk RNA-seq. We found a large number of gene profiles were altered following MSDC-0602K treatment in lungs. Interestingly, a number of genes accounting for pulmonary inflammatory responses were significantly decreased following MSDC-0602K treatment in lungs of db/db mice at day 5 post influenza virus infection. Moreover, MSDC-0602K treated lung tissue showed lower levels of genes related to glucose metabolism.
Project description:GLP-1 agonists are potent glucose-lowering agents, however, their effect on adolescent organisms needs to be clarified Transgenic pigs expressing a dominant-negative GLP receptor randomly assigned for a 90 day treatment trial with liraglutide (0.6-1.8 mg per day)/placebo
Project description:The objective of this study is to characterize the response to newly emerged, highly pathogenic H7N9 influenza virus isolated from human patients in 2013 in China. This study examines the pathogenesis of H7N9 influenza in cynomolgus macaques. The study compares lung lesions to adjacent right lower lobe lung tissue in animals necropsied at days 3 and 6 post-infection (n=4 animals/timepoint). 3-4 lesions from each animal were collected and equal amounts of pooled RNA from lesions from individual animals at each time point were used for microarray. 8 cynomolgus macaques were infected via oral, intraocular, intranasal, and intratracheal administration of a combined total of 7x10^6 TCID50. Lungs, lung lesions, and trachea samples were collected from serial sacrifices of 4 animals each at day 3 and day 6. Infection produced a moderate-severe, self-limiting respiratory infection, and was not lethal. We performed microarray analysis (using Agilent Rhesus arrays) on all lungs, lung lesions, and trachea collected for the study.
Project description:These data were generated as part of a study to model gene regulatory networks influenced by influenza infection. Other tissue compartments included in the study were blood, lung, and lymph node. RNA was extracted from spleens of female mice that did not have any experimental treatment (n = 3, labeled as T-9) or that received intranasal administration of influenza A virus either immediately before (n = 3, T0) or 1 to 10 days before being euthanized for tissue collection (T1 through T10, n =3-4 per day). Gene expression profiles were determined with comprehensive microarrays (Affymetrix Mouse Gene ST 1.0).