• Influence of infection route and virulence factors on colonization of solid tumors by Salmonella enterica serovar Typhimurium.

      Crull, Katja; Bumann, Dirk; Weiss, Siegfried; Dept. Molecular Immunology, Helmholtz Centre for infection research, Inhoffenstr. 7, D38124 Braunschweig, Germany. (2011-06)
      Administration of facultative anaerobic bacteria such as Salmonella enterica serovar Typhimurium as anticancer treatment holds a great therapeutic potential. Here, we tested different routes of application of S. typhimurium with regard to tumor colonization and therapeutic efficacy. No differences between intravenous and intraperitoneal infection were observed, often leading to a complete tumor clearance. In contrast, after oral application, tumor colonization was inefficient and delayed. No therapeutic effect was observed under such conditions. We also showed that tumor invasion and colonization were independent of functional Salmonella pathogenicity island (SPI) 1 and SPI 2. Furthermore, tumor invasion and colonization did not require bacterial motility or chemotactic responsiveness. The distribution of the bacteria within the tumor was independent of such functions.
    • Strong interferon-inducing capacity of a highly virulent variant of influenza A virus strain PR8 with deletions in the NS1 gene.

      Kochs, Georg; Martínez-Sobrido, Luis; Lienenklaus, Stefan; Weiss, Siegfried; García-Sastre, Adolfo; Staeheli, Peter; Department of Virology, University of Freiburg, D-79008 Freiburg, Germany. georg.kochs@uniklinik-freiburg.de (2009-12)
      Influenza viruses lacking the interferon (IFN)-antagonistic non-structural NS1 protein are strongly attenuated. Here, we show that mutants of a highly virulent variant of A/PR/8/34 (H1N1) carrying either a complete deletion or C-terminal truncations of NS1 were far more potent inducers of IFN in infected mice than NS1 mutants derived from standard A/PR/8/34. Efficient induction of IFN correlated with successful initial virus replication in mouse lungs, indicating that the IFN response is boosted by enhanced viral activity. As the new NS1 mutants can be handled in standard biosafety laboratories, they represent convenient novel tools for studying virus-induced IFN expression in vivo.