A Plant Extract of Ribes nigrum folium Possesses Anti-Influenza Virus Activity In Vitro and In Vivo by Preventing Virus Entry to Host Cells

Infections with influenza A viruses (IAV) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. Besides vaccination that represents the best option to protect from IAV infections, only two classes of anti-influenza drugs, inhibitors of the M2 ion channel and the neuraminidase, often causing resistant IAV variants have been approved. That is why the need for effective and amply available antivirals against IAV is of high priority. Here we introduce LADANIA067 from the leaves of the wild black currant (Ribes nigrum folium) as a potent compound against IAV infections in vitro and in vivo. LADANIA067 treatment resulted in a reduction of progeny virus titers in cell cultures infected with prototype avian and human influenza virus strains of different subtypes. At the effective dose of 100 µg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation. Further, viruses showed no tendency to develop resistance to LADANIA067 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of LADANIA067 appears to be mainly due to interference with virus internalisation. In the mouse infection model LADANIA067 treatment reduces progeny virus titers in the lung upon intranasal application. In conclusion, an extract from the leaves of the wild black currant might be a promising source for the development of new antiviral compounds to fight IAV infections

Reduced Bcl-x expression correlates with enhanced caspase-3 activation in NF-κB2- and Bcl-3-deficient mice after 11 weeks of PrP infection

<p><b>Copyright information:</b></p><p>Taken from "Alteration of NF-κB activity leads to mitochondrial apoptosis after infection with pathological prion protein"</p><p></p><p>Cellular Microbiology 2007;9(9):2202-2217.</p><p>Published online 15 Jun 2007</p><p>PMCID:PMC2048569.</p><p>© 2007 The Authors; Journal compilation © 2007 Blackwell Publishing Ltd</p> A. Bcl-x expression (black arrows), active cleaved caspase-9 and caspase-3 were determined by immunohistological staining. , , and C57Bl/6 mice were inoculated with RML6 and three animals per groups were sacrificed at 11 weeks p.i. Brain sections of three animals were analysed for each mouse line. Representative areas of the entorhinal cortex are shown. Magnification ×20. B and C. For quantification of positive cells, three sections of three different mouse brains for each strain were chosen. The graphic represents the amount of positive cells in the brain of the deficient mice compared with the C57Bl/6 mice in percentage of control. SEM was shown as bars. For detailed information on quantification see

Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as a Prerequisite for Canine T Cell Immunotherapy.

There are limitations in pre-clinical settings using mice as a basis for clinical development in humans. In cancer, similarities exist between humans and dogs; thus, the dog patient can be a link in the transition from laboratory research on mouse models to clinical trials in humans. Knowledge of the peptides presented on MHC molecules is fundamental for the development of highly specific T cell-based immunotherapies. This information is available for human MHC molecules but is absent for the canine MHC. In the present study, we characterized the binding motif of dog leukocyte antigen (DLA) class I allele DLA-88*50101, using human C1R and K562 transfected cells expressing the DLA-88*50101 heavy chain. MHC class I immunoaffinity-purification revealed 3720 DLA-88*50101 derived peptides, which enabled the determination of major anchor positions. The characterized binding motif of DLA-88*50101 was similar to HLA-A*02:01. Peptide binding analyses on HLA-A*02:01 and DLA-88*50101 via flow cytometry showed weak binding of DLA-88*50101 derived peptides to HLA-A*02:01, and vice versa. Our results present for the first time a detailed peptide binding motif of the canine MHC class I allelic product DLA-88*50101. These data support the goal of establishing dogs as a suitable animal model for the evaluation and development of T cell-based cancer immunotherapies, benefiting both dog and human patients