MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies

Generation of Up to Date Land Cover Maps for Central Asia

Human activity and climate variability has always changed the Earth’s surface and both will mainly contribute to future alteration in land cover and land use changes. In this chapte we demonstrate a land cover and land use classification approach for Central Asia addressing regional characteristics of the study area. With the aim of regional classification map for Central Asia a specific classification scheme based on the Land Cover Classification System (LCCS) of the Food and Agriculture Organisation of the United Nations Environment Programme (FAO-UNEP) was developed. The classification was performed by using a supervised classification method applied on metrics, which were derived from Moderate Resolution Imaging Spectroradiometer (MODIS) data with 250 m spatial resolution. The metrics wer derived from annual time-series of red and nearinfrared reflectance as well as from Normalized Difference Vegetation Index (NDVI) and thus reflect the temporal behavior of different land cover types. Reference data required for a supervised classification approach were collected from several high resolution satellite imagery distributed all over the study area. The overall accuracy results for performed classification of the year 2001 and 2009 are 91.2 and 91.3 %. The comparison of both classification maps shows significant alterations for different classes. Water bodies such as Shardara Water Reservoir and Aral Sea have changed in their extent. Whereby, the size of the Shardara Water Reservoir is very dynamic from year to year due to water management and the eastern lobe of southern Aral Sea has decreased because of the lack of inflow from Amu Darja. Furthermore, some large scale changes were detected in sparsely vegetated areas in Turkmenistan, where spring precipitation mainly affects the vegetation density. In the north of Kazakhstan significant forest losses caused by forest fires and logging were detected. The presented classification approach is a suitable tool for monitoring land cover and land use in Central Asia. Such independent information is important for accurate assessment of water and land recourses

Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets

<div><p>Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.</p></div