Die Bedeutung des Mx-Proteins in der Influenza-Abwehr beim Huhn

Schusser, Benjamin (2010): Die Bedeutung des Mx-Proteins in der Influenza-Abwehr beim Huhn. Dissertation, LMU München: Tierärztliche Fakultät

Abstract

Influenza A virus infections are a major threat to the world poultry population. In the 19th century fatal influenza A virus infections have been described under the name “fowl plague” in chickens. The chicken is a natural host for this viral infection. The myxovirus resistance (Mx) gene which belongs to the group of interferon stimulated genes (ISG) was first described in mice. This protein confers protection against highly pathogenic influenza A viruses in mice. Mx proteins have been characterized in many species including mammals, poultry and fish. They belong to the family of large GTPase proteins exhibiting three highly conserved GTP-binding motifs at the amino-terminus and a leucin zipper at the carboxy-terminus. The GTPase activity was been shown to be essential for the antiviral activity of the Mx protein. Mx was also identified in the chicken, where it shows a significant degree of polymorphism. A polymorphism at aminoacid position 631 (serin versus asparagin) is thought to confer antiviral activity towards influenza A viruses. With the help of the RCAS retroviral vector system these two different chMx isoforms were examined in vitro and in vivo for their antiviral activity towards various pathogenic influenza A viruses. Neither in vitro nor in vivo antiviral activity of the chMx isoforms was detectable. In contrast overexpression of murine Mx1 and human MxA in the same form led to protection of the chicken embryo fibroblast cultures against influenza A viruses. Stimulation of chicken embryo fibroblasts with type I interferon induced chMx mRNA and protein expression as well as an antiviral state of the cells. However a chMx knock down mediated by siRNA did not lead to the loss of the antiviral state mediated by type I interferon. In summary, the in vitro studies did not provide evidence for a role of chMx in the antiviral state induced by type I interferon.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Influenza,Mx,RCAS,Huhn
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 590 Tiere (Zoologie)
• Fakultäten: Tierärztliche Fakultät
• Sprache der Hochschulschrift: Deutsch
• Datum der mündlichen Prüfung: 24. Juli 2010
• 1. Bericht­erstatter:in: Kaspers, Bernd