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

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.